Home
| Id ↑ | Rare Disease Name ↑ | Image↑ | Prevalance ↑ | Associated Genes↑ | Aliases↑ | Disease Description↑ | Gene Descriptions↑ | Cell Line↑ | |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 15q13.3 microdeletion syndrome Burnside-Butler syndrome | 1 in 40,000 to 1 in 100,000 individuals in the general population | CHRNA7 | Alpha-7 nicotinic acetylcholine receptor Neuronal acetylcholine receptor subunit alpha-7 Neuronal nicotinic acetylcholine receptor alpha-7 subunit Nicotinic cholinergic receptor alpha-7 subunit Acetylcholine receptor subunit alpha-7 NACHRA7 A7-nAChR nAChR α7 Alpha7 nAChR CHRNA7 protein | 15q13.3 microdeletion syndrome, or Burnside-Butler syndrome, is a genetic disorder due to a deletion on chromosome 15 at region 15q13.3, either de novo or inherited. It leads to developmental delays, intellectual disabilities, autism spectrum disorder, ADHD, anxiety, seizures, and psychiatric disorders like schizophrenia. Physical features may include subtle facial differences, hypotonia, and possible congenital heart defects. Diagnosis involves genetic testing and clinical evaluation. Management includes early intervention, medical treatment, special education, and behavioral therapy. Prognosis varies, and genetic counseling is recommended for affected families | cholinergic receptor nicotinic alpha 7 subunit | SH-SY5Y- Human neuroblastoma cells often used in studies of neurobiology. PC12 - Rat pheochromocytoma cells commonly used in studies of neuronal differentiation. C2C12 - Mouse myoblast cells used in studies of muscle biology. | ||
| 2 | 15q24 microdeletion syndrome Chromosome 15q24 deletion syndrome | fewer than 1 in 100,000 individuals | SIN3A | hSIN3A,mSin3A | 15q24 microdeletion syndrome is a rare genetic disorder caused by a deletion in chromosome 15 at the q24 region, leading to developmental delays, intellectual disability, characteristic facial features, congenital malformations, and behavioral issues. Diagnosis is typically through genetic testing, and most cases are de novo. Management involves a multidisciplinary approach with therapies and interventions to address medical and developmental needs. Prognosis varies based on the severity of symptoms, but early and comprehensive care can improve outcomes. | SIN3 transcription regulator family member A | PC12 - Rat pheochromocytoma cells. NIH 3T3 - Mouse fibroblast cells. BJ - Human foreskin fibroblast cells. BJ - Human foreskin fibroblast cells.THP-1 - Human monocytic cells. | ||
| 3 | 17p11.2 microduplication syndrome Potocki-Lupski syndrome (PTLS) | fewer than 200 cases reported in the medical literature | SMCR (Smith-Magenis syndrome chromosome region), Retinoic acid-induced 1 Retinoic acid-induced protein 1-like MDS (Mental retardation, autosomal dominant 17) 17p11.2 microdeletion syndrome candidate gene 2 | 17p11.2 microduplication syndrome is a rare genetic disorder caused by a duplication of a segment on chromosome 17 at the p11.2 region. This condition is characterized by developmental delays, intellectual disability, speech and motor skill impairments, behavioral problems, and distinctive facial features. Diagnosis is confirmed through genetic testing, typically chromosomal microarray analysis. Most cases are de novo, though some can be inherited. Management involves a multidisciplinary approach with various therapies to support development and address medical issues. Prognosis varies depending on the duplication's impact, but supportive care can enhance quality of life. | retinoic acid induced 1 | HeLa (cervical cancer cells). HEK293 (human embryonic kidney cells). PC12 (pheochromocytoma cells). C6 (glioma cells). NRK (Normal Rat Kidney cells). | |||
| 4 | 17q11 microdeletion syndrome neurofibromatosis type 1 microdeletion syndrome | 1 in 3,000 to 1 in 4,000 individuals worldwide | NF1 | von Recklinghausen neurofibromatosis gene | 17q11 microdeletion syndrome, also known as NF1 microdeletion syndrome or neurofibromatosis type 1 microdeletion syndrome, is a genetic disorder characterized by the deletion of a segment on chromosome 17 at the q11 region. This condition shares some features with neurofibromatosis type 1 (NF1) but also has distinct characteristics. Common symptoms include developmental delays, intellectual disability, learning difficulties, distinctive facial features, and an increased risk of neurofibromas and other tumors. Diagnosis is typically made through genetic testing, specifically detecting the deletion in the NF1 gene region. Management involves a multidisciplinary approach to address medical, developmental, and psychological needs. Prognosis varies depending on the severity of symptoms and associated complications. | neurofibromin 1 | SH-SY5Y - Human neuroblastoma cells. SK-N-SH - Human neuroblastoma cells. PC12 - Rat pheochromocytoma cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. | ||
| 5 | 17q12 microdeletion syndrome renal cysts and diabetes (RCAD) syndrome or renal cysts and diabetes syndrome | The prevalence of renal cysts and diabetes (RCAD) syndrome is estimated to be relatively low, with reported rates varying among different populations. Studies have suggested that RCAD syndrome accounts for a small percentage of cases of early-onset diabetes and renal cystic diseases | HNF1B;LHX1 | Hepatocyte nuclear factor 1-beta Transcription factor 2 TCF-2 MODY5 (Maturity-Onset Diabetes of the Young 5) gene | Renal cysts and diabetes (RCAD) syndrome, also known as renal cysts and diabetes syndrome, is a genetic disorder characterized by the presence of renal cysts, early-onset diabetes, and, in some cases, other renal and extrarenal manifestations. It is caused by mutations in the HNF1B gene. Diagnosis is confirmed through genetic testing. The syndrome can be inherited in an autosomal dominant pattern. Management involves monitoring and treating diabetes and renal issues, and regular follow-up with a multidisciplinary team. Prognosis varies based on the severity of renal and diabetic complications, but early detection and management can improve outcomes | HNF1 homeobox B;LIM homeobox 1 | HepG2 (hepatocellular carcinoma cells). HeLa (cervical cancer cells). HEK293 (human embryonic kidney cells). NRK-52E (Normal Rat Kidney cells). BRL-3A (rat liver cells). RIN-m5F (rat insulinoma cells). | ||
| 6 | 22q11.2 deletion syndrome DiGeorge syndrome, velocardiofacial syndrome (VCFS), or conotruncal anomaly face syndrome | 1 in 4,000 live births, making it one of the most common chromosomal microdeletion syndromes | ARVCF;JMJD1C;UFD1;COMT;TBX1;HIRA;GP1BB;RREB1;SEC24C | ARVCF: Armadillo Repeat gene deleted in Velo-Cardio-Facial syndrome. JMJD1C: Jumonji domain containing 1C. UFD1: Ubiquitin fusion degradation protein 1 homolog. COMT: Catechol-O-methyltransferase. TBX1: T-box transcription factor TBX1. HIRA: Histone cell cycle regulation-defective homolog A. GP1BB: Glycoprotein Ib platelet beta subunit. RREB1: Ras-responsive element-binding protein 1. SEC24C: SEC24 homolog C, COPII coat complex component | 22q11.2 deletion syndrome, also known as DiGeorge syndrome or velocardiofacial syndrome, is a genetic disorder caused by a deletion of a small segment on chromosome 22 at the q11.2 region. This syndrome presents with a wide range of symptoms, including congenital heart defects, characteristic facial features, developmental delays, intellectual disability, immune system deficiencies, and palate abnormalities. Other potential features include hearing loss, feeding difficulties, and psychiatric disorders such as schizophrenia. Diagnosis is typically made through genetic testing, and management involves a multidisciplinary approach to address the various medical, developmental, and psychological needs of affected individuals. Prognosis varies widely depending on the severity of symptoms and the presence of associated complications. | ARVCF delta catenin family member;jumonji domain containing 1C;ubiquitin recognition factor in ER associated degradation 1;catechol-O-methyltransferase;T-box transcription factor 1;histone cell cycle regulator;glycoprotein Ib platelet subunit beta;ras responsive element binding protein 1;SEC24 homolog C, COPII coat complex component | N2A (Neuro-2a) - Mouse neuroblastoma cells. SH-SY5Y - Human neuroblastoma cells. PC-3 - Human prostate cancer cells. | ||
| 7 | 2q23.1 microdeletion syndrome Albright hereditary osteodystrophy-like syndrome | The prevalence of 2q23.1 microdeletion syndrome is not precisely known due to its rarity | MBD5 | KIAA1461 MGC129648 Protein containing methyl-CpG-binding domain 5 | 2q23.1 microdeletion syndrome is a rare genetic disorder characterized by the deletion of a segment on chromosome 2 at the q23.1 region. This syndrome presents with a spectrum of clinical features including developmental delays, intellectual disability, speech and motor impairments, growth abnormalities, distinctive facial features, and congenital malformations such as heart defects and skeletal anomalies. Diagnosis is typically confirmed through genetic testing, particularly chromosomal microarray analysis. Management involves a multidisciplinary approach to address medical, developmental, and behavioral issues | methyl-CpG binding domain protein 5 | SH-SY5Y - Human neuroblastoma cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. PC12 - Rat pheochromocytoma cells. | ||
| 8 | 3-methylcrotonyl-CoA carboxylase deficiency MCC deficiency or 3-MCC deficiency | 1 in 50,000 to 1 in 150,000 newborns worldwid | MCCC1;MCCC2 | MCCC1: 3-Methylcrotonoyl-CoA carboxylase 1 3MCC1 Methylcrotonyl-CoA carboxylase subunit alpha MCCC2: 3-Methylcrotonoyl-CoA carboxylase 2 3MCC2 Methylcrotonyl-CoA carboxylase subunit beta | 3-Methylcrotonyl-CoA carboxylase deficiency (3-MCC deficiency) is a rare inherited metabolic disorder characterized by the body's inability to break down the amino acid leucine properly. This condition is caused by mutations in the MCCC1 or MCCC2 genes, which encode the subunits of the enzyme 3-methylcrotonyl-CoA carboxylase. As a result, toxic byproducts accumulate in the body, leading to symptoms such as recurrent episodes of metabolic decompensation, including vomiting, dehydration, lethargy, and neurological abnormalities. Diagnosis is typically made through biochemical testing, including blood and urine tests, and confirmed by genetic testing. Management involves a low-protein diet, supplementation with carnitine and other nutrients, and prompt treatment of metabolic crises with intravenous fluids and glucose. With early detection and appropriate management, individuals with 3-MCC deficiency can lead relatively normal lives, although they may still be at risk for metabolic crises during periods of illness or stress. | methylcrotonyl-CoA carboxylase subunit 1;methylcrotonyl-CoA carboxylase subunit 2 | SH-SY5Y - Human neuroblastoma cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. C2C12 - Mouse myoblast cells. | ||
| 9 | 3M syndrome Miller-McKusick-Malvaux syndrome | less than 1 in 1,000,000 individuals | OBSL1;CUL7;CCDC8 | OBSL1: Obscurin-like 1 hObs KIAA0896 CUL7: Cullin 7 Cullin-7 CUL-7 CCDC8: Coiled-Coil Domain Containing 8 Coiled-coil domain-containing protein 8 FLJ10781 | Miller-McKusick-Malvaux syndrome, also known as Carpenter-Waziri syndrome, is a rare genetic disorder characterized by intellectual disability, craniofacial abnormalities, skeletal anomalies, and other developmental abnormalities. It is caused by mutations in the IFT80 gene, which plays a role in intraflagellar transport and ciliogenesis. Common features include microcephaly, brachydactyly, syndactyly, and distinctive facial features such as a broad nasal bridge and prominent forehead. Diagnosis is typically made based on clinical presentation and confirmed through genetic testing. Management involves multidisciplinary care to address the various medical and developmental needs of affected individuals | obscurin like cytoskeletal adaptor 1;cullin 7;coiled-coil domain containing 8 | SH-SY5Y - Human neuroblastoma cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. THP-1 - Human monocytic cells. C2C12 - Mouse myoblast cells. L6 - Rat myoblast cells. | ||
| 10 | 46,XX testicular disorder of sex development Swyer syndrome | approximately 1 in 20,000 to 1 in 90,000 live births | NR0B1;SRY;NR5A1;SOX9;SOX3 | NR0B1: DAX1 (Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) Adrenal hypoplasia congenita critical region on chromosome X, gene 1 AHCH AHC DSS SRY: Sex-determining region Y Testis-determining factor TDY NR5A1: Steroidogenic factor 1 SF-1 Adrenal 4-binding protein Ad4BP SOX9: SRY-box transcription factor 9 Campomelic dysplasia autosomal sex reversal CMD1 SRA1 SOX3: SRY-box transcription factor 3 LXP SRY-related HMG-box gene 3 | 46,XX testicular disorder of sex development (DSD), also known as XX male syndrome, is a rare condition where individuals with a 46,XX karyotype typically associated with females develop testes instead of ovaries. Despite having the typical male gonads, affected individuals may exhibit external genitalia that appear female or ambiguous. This condition is often caused by mutations in genes involved in sex determination and differentiation pathways. Diagnosis involves genetic testing and evaluation of reproductive anatomy. Management may include hormone replacement therapy and surgical interventions to align gender identity with physical characteristics | nuclear receptor subfamily 0 group B member 1;sex determining region Y;nuclear receptor subfamily 5 group A member 1;SRY-box transcription factor 9;SRY-box transcription factor 3 | HeLa (cervical cancer cells). HEK293 (human embryonic kidney cells). R2C (Leydig tumor cells). PC12 (pheochromocytoma cells). BRL-3A (rat liver cells) | ||
| 11 | 46,XY complete gonadal dysgenesis Swyer syndrome | estimated to be around 1 in 150,000 to 1 in 200,000 live births | WT1;CBX2;DHX37;DHH;DMRT1;NR5A1;NR0B1;MAP3K1;SOX9;SRY | WT1: Wilms tumor 1 WAGR WIT-2 NPHS4 CBX2: Chromobox 2 HP1-beta HP1Hsbeta DHX37: DEAH-box helicase 37 DDX37 DHH: Desert hedgehog homolog DHHB HPE3 DMRT1: Doublesex- and mab-3-related transcription factor 1 Dmrt7 DMRTA1 NR5A1: Nuclear receptor subfamily 5 group A member 1 SF-1 Adrenal 4-binding protein Ad4BP FTZ-F1 SF1 NR0B1: Nuclear receptor subfamily 0 group B member 1 DAX1 AHCH MAP3K1: Mitogen-activated protein kinase kinase kinase 1 MEKK1 MAPKKK1 SOX9: SRY-box transcription factor 9 CMD1 SRA1 SRY: Sex-determining region Y TDY | 46,XY complete gonadal dysgenesis is a rare genetic disorder characterized by individuals with a male chromosomal pattern (46,XY) who have underdeveloped or absent gonads, resulting in incomplete or absent development of male reproductive structures. This condition typically presents with ambiguous genitalia at birth and is often associated with primary amenorrhea in affected individuals assigned female at birth. It is caused by mutations in genes involved in the development of the gonads, such as SRY or other genes on the Y chromosome, leading to gonadal dysgenesis. Diagnosis is confirmed through genetic testing and imaging studies. Management involves hormone replacement therapy to induce secondary sexual characteristics and address potential complications such as osteoporosis | WT1 transcription factor;chromobox 2;DEAH-box helicase 37;desert hedgehog signaling molecule;doublesex and mab-3 related transcription factor 1;nuclear receptor subfamily 5 group A member 1;nuclear receptor subfamily 0 group B member 1;mitogen-activated protein kinase kinase kinase 1;SRY-box transcription factor 9;sex determining region Y | A549 - Human lung carcinoma cells. NIH 3T3 - Mouse fibroblast cells. | ||
| 12 | 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency 5-alpha-reductase deficiency or simply 5-ARD | estimated to be approximately 1 in 130,000 to 1 in 150,000 births worldwide | SRD5A2 | SRD5A2: Steroid 5-alpha-reductase 2 5-ARD 5-alpha reductase type 2 | 5-alpha-reductase deficiency (5-ARD) is a genetic condition characterized by the impaired function of the enzyme 5-alpha-reductase, which is responsible for converting testosterone into dihydrotestosterone (DHT). This deficiency leads to a disruption in the development of male sex characteristics in individuals assigned male at birth. Common features include ambiguous genitalia at birth, varying degrees of virilization during puberty, and infertility in individuals with severe forms of the condition. Diagnosis is typically made through hormone testing and genetic analysis. Management may involve hormone replacement therapy and surgical interventions to address genital ambiguity. With appropriate treatment, individuals with 5-ARD can lead healthy lives | steroid 5 alpha-reductase 2 | PC-3 - Human prostate cancer cells. HepG2 - Human liver carcinoma cells. HaCaT - Immortalized human keratinocyte cells. | ||
| 13 | 46,xy sex reversal 2 Testicular Regression Syndrome or TRS | approximately 1 in 20,000 to 1 in 30,000 live births | NR0B1 | DAX1 (Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) Adrenal hypoplasia congenita critical region on chromosome X, gene 1 AHCH AHC DSS | 46,XY sex reversal 2, also known as SRXY2, is a genetic disorder characterized by individuals with a 46,XY karyotype (typically associated with males) who develop characteristics typical of females. This condition is caused by mutations in certain genes involved in sex determination and differentiation, leading to incomplete or ambiguous development of the external genitalia. Individuals with SRXY2 may have varying degrees of undervirilization, ranging from mild genital ambiguity to complete female external genitalia. Diagnosis is typically made through genetic testing to identify mutations in genes such as NR5A1 or MAP3K1. Management involves a multidisciplinary approach with medical and psychological support, and treatment may include hormone therapy and surgical interventions to align physical appearance with gender identity. Prognosis depends on the specific genetic and anatomical features of each individual | nuclear receptor subfamily 0 group B member 1 | HeLa (cervical cancer cells). HEK293 (human embryonic kidney cells). R2C (Leydig tumor cells). PC12 (pheochromocytoma cells). BRL-3A (rat liver cells) | ||
| 14 | Abetalipoproteinemia Bassen-Kornzweig syndrome | approximately 1 in 1,000,000 individuals worldwide | MTTP | Microsomal triglyceride transfer protein MTP MTTP | Abetalipoproteinemia is a rare genetic disorder characterized by the body's inability to properly absorb dietary fats, cholesterol, and fat-soluble vitamins. It is caused by mutations in the microsomal triglyceride transfer protein (MTTP) gene, which plays a crucial role in the assembly and secretion of lipoproteins. Common symptoms include fat malabsorption leading to steatorrhea (excessive fat in feces), failure to thrive, neurological abnormalities, and vision problems due to vitamin deficiencies. Diagnosis is often based on clinical symptoms, lipid profiles, and genetic testing. Treatment typically involves lifelong dietary modifications, supplementation with fat-soluble vitamins, and management of associated complications | microsomal triglyceride transfer protein | HepG2 - Human liver carcinoma cells. HT-29 - Human colorectal adenocarcinoma cells. HEK293 - Human embryonic kidney cells (often used in transfection studies, including those involving MTTP). | ||
| 15 | Acheiropodia Limb-Body Wall Complex | 1 in 10 million births worldwide | LMBR1 | Limb region 1 homolog LIMR Limb development membrane protein 1 | Acheiropodia is an extremely rare genetic disorder characterized by the absence of hands and feet at birth. Affected individuals typically have well-formed forearms and lower legs that end abruptly, often described as "flippers." This condition is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to be affected. While the exact genetic cause is not fully understood, mutations in the LMBR1 gene have been implicated in some cases | limb development membrane protein 1 | HEK293 (human embryonic kidney cells). HeLa (cervical cancer cells). A549 (lung carcinoma cells). PC12 (pheochromocytoma cells). RBL-2H3 (rat basophilic leukemia cells). NRK-52E (Normal Rat Kidney cells). | ||
| 16 | Acquired idiopathic sideroblastic anemia primary acquired sideroblastic anemia (PASA) | 1 to 2 cases per 100,000 individuals in the general population | SF3B1;TET2 | SF3B1: Splicing factor 3B subunit 1 SAP155 (SR-related protein associated with the spliceosome) SF3B155 TET2: Tet methylcytosine dioxygenase 2 Jumonji domain-containing protein D2 LCX (leukemia-associated protein with a CXXC domain) KIAA1546 | Acquired idiopathic sideroblastic anemia (AISA) is a type of anemia characterized by the presence of ringed sideroblasts in the bone marrow, which are erythroblasts with abnormal iron accumulation. Unlike hereditary forms of sideroblastic anemia, the acquired form has no known underlying genetic cause and is typically seen in adults. Common symptoms include fatigue, weakness, pallor, and shortness of breath. Diagnosis involves blood tests, bone marrow examination, and ruling out other causes of anemia. Treatment options may include iron chelation therapy, erythropoiesis-stimulating agents, and blood transfusions, depending on the severity of symptoms and underlying factors | splicing factor 3b subunit 1;tet methylcytosine dioxygenase 2 | HeLa (cervical cancer cells). HEK293 (human embryonic kidney cells). A549 (lung carcinoma cells). PC12 (pheochromocytoma cells). NRK-52E (Normal Rat Kidney cells). BRL-3A (rat liver cells). | ||
| 17 | Acquired partial lipodystrophy Barraquer-Simons syndrome | 1–9 in 100,000 population | LMNB2 | Lamin B2 | Barraquer-Simons syndrome, also known as lipodystrophy acquired partial, is a rare disorder characterized by the selective loss of subcutaneous fat, leading to a lean appearance with prominent veins and muscles. Individuals with this syndrome may experience metabolic abnormalities such as insulin resistance, hypertriglyceridemia, and liver steatosis. The exact cause of Barraquer-Simons syndrome is not fully understood, but it is thought to involve a combination of genetic and environmental factors. Treatment focuses on managing associated metabolic complications and may include lifestyle modifications, medications, and monitoring for potential complications such as diabetes and cardiovascular disease | lamin B2 | N2A (Neuro-2a) - Mouse neuroblastoma cells. THP-1 - Human monocytic cells. HeLa - Human cervical cancer cells. PC-3 - Human prostate cancer cells. | ||
| 18 | Acrocallosal syndrome Schinzel syndrome | 1 in 1 million individuals | GLI3;KIF7 | Kinesin family member 7 KIAA1456 | Acrocallosal syndrome is a rare genetic disorder characterized by a combination of physical, neurological, and developmental abnormalities. It is typically caused by mutations in the KIF7 gene. Common features include craniofacial anomalies such as a prominent forehead, widely spaced eyes, and a flat nasal bridge, as well as limb malformations like extra fingers or toes (polydactyly). Individuals with acrocallosal syndrome may also have intellectual disability, delays in motor skills development, and structural brain abnormalities including absence or underdevelopment of the corpus callosum, which connects the brain's hemispheres. Management typically involves addressing medical and developmental needs through a multidisciplinary approach, including surgical interventions for limb anomalies and supportive therapies for developmental delays. Prognosis varies depending on the severity of symptoms, but with appropriate care, many individuals with acrocallosal syndrome can lead fulfilling lives. | GLI family zinc finger 3;kinesin family member 7 | |||
| 19 | Acrodysostosis Maroteaux-Malamut syndrome | it affects fewer than 1 in 1 million people worldwide | PDE4D;PRKAR1A | PDE4D: Phosphodiesterase 4D DPDE3 DPDE3A PRKAR1A: cAMP-dependent protein kinase type I-alpha regulatory subunit PKR1 TSE1 | Acrodysostosis is a rare genetic disorder characterized by skeletal abnormalities, including shortened bones in the hands and feet, facial dysostosis, and nasal hypoplasia. It often presents with short stature, intellectual disability, and hormone resistance, particularly to parathyroid and thyroid hormones. The condition is typically caused by mutations in the PRKAR1A or PDE4D genes, which affect bone development and hormone signaling pathways. Diagnosis is based on clinical features, radiographic findings, and genetic testing | phosphodiesterase 4D;protein kinase cAMP-dependent type I regulatory subunit alpha | |||
| 20 | Acrofacial dysostosis, Weyers type Weyers acrodental dysostosis | Only a few affected families have been identified worldwide | EVC;EVC2 | Ellis-van Creveld syndrome protein Ellis-van Creveld syndrome 2 protein | Acrofacial dysostosis, Weyers type (WAD), is a rare genetic disorder characterized by abnormalities in the development of the bones of the face and limbs. Key features include: Short stature and short limbs (especially the lower legs and forearms). Dental anomalies, such as extra teeth (supernumerary teeth) and dental crowding. Nail dysplasia, often presenting as small or missing nails. Facial abnormalities, including a prominent forehead, small jaw (micrognathia), and sometimes a cleft palate. WAD is caused by mutations in the EVC or EVC2 genes and is inherited in an autosomal dominant pattern. The condition is part of a spectrum of disorders known as Ellis-van Creveld syndrome, with Weyers type being the milder form. | EvC ciliary complex subunit 1;EvC ciliary complex subunit 2 | |||
| 21 | Acrogeria Gottron syndrome | fewer than 50 reported cases in the medical literature worldwide | COL3A1 | Collagen type III alpha 1 chain EDS4A (Ehlers-Danlos syndrome type IV, autosomal dominant) Collagen III FLJ34534 | Acrogeria, also known as Gottron's syndrome, is a rare genetic disorder characterized by premature aging of the skin, primarily affecting the extremities such as the hands and feet. Individuals with this condition exhibit thin, wrinkled, and translucent skin, which makes their veins more prominent. The disorder also leads to a significant reduction in subcutaneous fat, contributing to the aged appearance of the affected areas. Joint abnormalities, including stiffness or deformities, may also be present. Acrogeria typically manifests in early childhood and progresses over time. It is usually inherited in an autosomal dominant pattern, though sporadic cases can occur. Currently, there is no cure for acrogeria, and treatment mainly focuses on managing symptoms and protecting the delicate skin. | collagen type III alpha 1 chain | |||
| 22 | Acromegaly Gigantism | about 40 to 60 cases per million people | GPR101;AIP | GPR101: G-protein coupled receptor 101 GPCR6 AIP: Aryl hydrocarbon receptor-interacting protein AIP1 AH receptor-interacting protein XAP2 (X-associated protein 2) ARA9 (AIP-related protein) | Acromegaly is a rare hormonal disorder that results from the overproduction of growth hormone (GH) by the pituitary gland, usually due to a benign tumor called a pituitary adenoma. This excess GH leads to the enlargement of bones and tissues, most notably in the hands, feet, and face. Symptoms include enlarged hands and feet, facial changes like protruding jaw and brow, thickened skin, and joint pain. Over time, acromegaly can cause serious health issues such as diabetes, hypertension, cardiovascular disease, and arthritis. Early diagnosis and treatment, typically involving surgery, medication, or radiation therapy, are crucial to managing the condition and preventing complications. | G protein-coupled receptor 101;aryl hydrocarbon receptor interacting protein | PC-3 - Human prostate cancer cells. A549 - Human lung carcinoma cells. NIH 3T3 - Mouse fibroblast cells. BJ - Human foreskin fibroblast cells. | ||
| 23 | Acromicric dysplasia Geleophysic dysplasia type 2 | fewer than 1 in 1,000,000 individuals worldwide | LTBP3;FBN1 | LTBP3: Latent transforming growth factor beta binding protein 3 LTBP-3 FBN1: Fibrillin 1 Marfan syndrome 1 MFS1 | Acromicric dysplasia is a rare genetic disorder characterized by skeletal abnormalities, short stature, distinctive facial features, and joint limitations. Individuals with acromicric dysplasia typically have short hands and feet with characteristic stubby fingers and toes, as well as a short stature relative to their peers. Facial features may include a round face with prominent cheeks, a small nose, and a relatively flat nasal bridge. Joint limitations, particularly in the hands and feet, can lead to difficulties with mobility and fine motor skills. This condition is caused by mutations in the FBN1 gene, which encodes a protein involved in the formation of connective tissue. While there is no cure for acromicric dysplasia, management typically focuses on addressing symptoms and improving quality of life through supportive care and interventions tailored to individual needs | latent transforming growth factor beta binding protein 3;fibrillin 1 | NIH 3T3 - Mouse fibroblast cells. A549 - Human lung carcinoma cells. HeLa - Human cervical cancer cells. | ||
| 24 | Activated PI3K-delta syndrome PI3KDelta-Activated Syndrome with Immunodeficiency | 1-2 affected people per million | PIK3CD;PTEN;PIK3R1 | PIK3CD: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta PI3Kδ PI3K-p110δ p110δ PTEN: Phosphatase and tensin homolog MMAC1 (Mutated in multiple advanced cancers 1) TEP1 (TGF-beta-regulated and epithelial cell-enriched phosphatase 1) PIK3R1: Phosphoinositide-3-kinase regulatory subunit 1 PI3K p85α GRB1 (Growth factor receptor-bound protein 1) p85α p55α p50α | Activated PI3K-delta syndrome (APDS) is a rare primary immunodeficiency disorder caused by gain-of-function mutations in the PIK3CD gene, leading to dysregulation of the phosphoinositide 3-kinase (PI3K) signaling pathway. This dysregulation results in hyperactivation of PI3K-delta, affecting various immune cell functions such as B cell development, T cell activation, and innate immune responses. Clinically, APDS is characterized by recurrent respiratory infections, lymphoproliferation, autoimmunity, and increased susceptibility to certain infections, particularly caused by encapsulated bacteria. Management typically involves immunoglobulin replacement therapy, antimicrobial prophylaxis, and, in some cases, targeted therapies aimed at modulating the PI3K pathway. Early diagnosis and appropriate management are crucial for optimizing outcomes in individuals with APDS. | phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta;phosphatase and tensin homolog;phosphoinositide-3-kinase regulatory subunit 1 | |||
| 25 | Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22) Acute Myeloid Leukemia with inv(16) | it represents approximately 5-8% of all AML cases | CBFB;FLT3;MYH11;KIT | CBFB: Core-binding factor beta PEBP2B (polyomavirus enhancer-binding protein 2, beta subunit) FLT3: FMS-like tyrosine kinase 3 CD135 FLK2 (Fetal liver kinase-2) STK1 (Stem cell tyrosine kinase 1) MYH11: Myosin heavy chain 11 AAT4 FAA4 SMHCA (Smooth muscle heavy chain A) KIT: KIT proto-oncogene receptor tyrosine kinase CD117 C-KIT SCFR (Stem cell factor receptor) | Acute Myeloid Leukemia (AML) with inv(16), also known as AML with core-binding factor (CBF) rearrangement, represents a subtype of AML characterized by a distinct genetic abnormality involving the inversion of chromosome 16. This inversion leads to the fusion of two genes: CBFB and MYH11, resulting in the formation of the CBFB-MYH11 fusion gene. Clinically, patients with AML inv(16) typically present with features such as eosinophilia, thrombocytopenia, and a favorable prognosis compared to other AML subtypes. The CBFB-MYH11 fusion protein disrupts normal hematopoietic differentiation by interfering with transcriptional regulation, ultimately contributing to leukemogenesis. Treatment for AML inv(16) often involves intensive chemotherapy regimens, with some patients also benefiting from allogeneic stem cell transplantation for consolidation therapy. Overall, AML with inv(16) represents a distinct molecular subtype of AML with its own clinical and therapeutic implications. | core-binding factor subunit beta;fms related receptor tyrosine kinase 3;myosin heavy chain 11;KIT proto-oncogene, receptor tyrosine kinase | |||
| 26 | Acute promyelocytic leukemia M3 acute myeloid leukemia (M3-AML) | IRF2BP2;BCOR;STAT5B;STAT3;PRKAR1A;RARA;FIP1L1;NABP1;TBL1XR1;NPM1;ZBTB16;NUMA1;PML | IRF2BP2: Interferon regulatory factor 2 binding protein 2 IRF2BP2 BCOR: BCL6 corepressor BCL6 interacting corepressor KIAA1575 STAT5B: Signal transducer and activator of transcription 5B STAT5B STAT3: Signal transducer and activator of transcription 3 STAT3 PRKAR1A: Protein kinase cAMP-dependent type I regulatory subunit alpha PRKAR1A RARA: Retinoic acid receptor alpha RARA FIP1L1: Factor interacting with PAPOLA and CPSF1 FIP1L1 NABP1: Nucleic acid binding protein 1 NABP1 TBL1XR1: Transducin beta-like 1 X-linked receptor 1 TBL1XR1 NPM1: Nucleophosmin 1 NPM1 ZBTB16: Zinc finger and BTB domain containing 16 ZBTB16 NUMA1: Nuclear mitotic apparatus protein 1 NUMA1 PML: Promyelocytic leukemia protein PML | Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by the abnormal accumulation of immature promyelocytes in the bone marrow and blood. It is distinguished by a specific chromosomal translocation, t(15;17), which results in the fusion of the promyelocytic leukemia (PML) gene on chromosome 15 with the retinoic acid receptor-alpha (RARα) gene on chromosome 17. This fusion leads to impaired differentiation and increased proliferation of promyelocytes. A hallmark of APL is its high sensitivity to treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which induce differentiation and apoptosis of leukemic cells, respectively, resulting in high rates of complete remission and overall survival. However, APL is also associated with a risk of life-threatening coagulopathy, necessitating prompt diagnosis and specialized management strategies. | interferon regulatory factor 2 binding protein 2;BCL6 corepressor;signal transducer and activator of transcription 5B;signal transducer and activator of transcription 3;protein kinase cAMP-dependent type I regulatory subunit alpha;retinoic acid receptor alpha;factor interacting with PAPOLA and CPSF1;nucleic acid binding protein 1;TBL1X receptor 1;nucleophosmin 1;zinc finger and BTB domain containing 16;nuclear mitotic apparatus protein 1;PML nuclear body scaffold | ||||
| 27 | Adams-Oliver syndrome Congenital scalp defects with terminal limb anomalies | fewer than 1 in 100,000 individuals affected worldwide | EOGT;DOCK6;ARHGAP31;NOTCH1;DLL4;RBPJ | EOGT: EGF domain-specific O-linked N-acetylglucosamine transferase EOGT1 EOGT2 EOGT3 DOCK6: Dedicator of cytokinesis protein 6 ZIR2 (Zinc finger protein regulated in stress) Zizimin2 FLJ21063 ARHGAP31: Rho GTPase-activating protein 31 RhoGAP36 FLJ10489 NOTCH1: Neurogenic locus notch homolog protein 1 TAN1 (Translocation-associated notch homolog 1) hN1 NOTCH DLL4: Delta-like protein 4 Delta4 RBPJ: Recombining binding protein suppressor of hairless CSL (C promoter-binding factor 1, Suppressor of hairless, Lag-1) RBPJK | Adams-Oliver syndrome (AOS) is a rare genetic disorder characterized by the combination of congenital scalp defects, often manifesting as missing patches of skin or abnormalities of the skull bones, and malformations of the limbs, such as absent or underdeveloped fingers or toes. Additional features may include cardiovascular abnormalities, such as heart defects or blood vessel abnormalities, as well as neurological complications. AOS is typically caused by mutations in genes involved in vascular development, leading to impaired blood vessel formation during embryonic development. The severity of AOS can vary widely among affected individuals, ranging from mild to severe manifestations. Treatment primarily focuses on addressing specific symptoms and may involve surgical interventions to correct limb or scalp defects, as well as management of associated health issues. | EGF domain specific O-linked N-acetylglucosamine transferase;dedicator of cytokinesis 6;Rho GTPase activating protein 31;notch receptor 1;delta like canonical Notch ligand 4;recombination signal binding protein for immunoglobulin kappa J region | NIH 3T3 - Mouse fibroblast cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. HeLa - Human cervical cancer cells. PC-3 - Human prostate cancer cells. | ||
| 28 | Adrenocortical carcinoma Adrenal cortex carcinoma | 0.5 to 2 cases per million individuals per year | TP53 | Tumor protein p53 p53 Transformation-related protein 53 Antigen NY-CO-13 | Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy arising from the adrenal cortex, typically presenting with hormonal dysregulation and/or symptoms related to tumor growth. It accounts for only a small fraction of adrenal tumors, with an annual incidence of 0.5-2 cases per million individuals. ACC commonly manifests with symptoms such as abdominal pain, weight loss, and hormonal imbalances due to excessive production of adrenal hormones, including cortisol, aldosterone, and androgens. Diagnosis often involves imaging studies like CT or MRI, along with hormonal assays and biopsy confirmation. Treatment options vary based on the tumor stage but may include surgery, chemotherapy, and targeted therapies, with prognosis heavily dependent on the disease stage at diagnosis and the effectiveness of treatment interventions. | tumor protein p53 | |||
| 29 | Adrenomyeloneuropathy Addison disease, X-linked, with cerebral sclerosis | 1 in 20,000 to 1 in 40,000 individuals | ABCD1 | ATP-binding cassette sub-family D member 1 ALDP (Adrenoleukodystrophy protein) ALD protein ALDPX (Adrenoleukodystrophy protein X) | Adrenomyeloneuropathy (AMN) is a rare genetic disorder characterized by the progressive degeneration of the spinal cord, adrenal gland dysfunction, and peripheral neuropathy. It is a subtype of adrenoleukodystrophy (ALD), primarily affecting adult males, although females can also be affected. AMN typically presents with symptoms such as stiffness, weakness, and pain in the legs, as well as bladder and bowel dysfunction. Adrenal insufficiency, leading to hormonal imbalances, is another hallmark feature. The condition is caused by mutations in the ABCD1 gene, resulting in the accumulation of very long-chain fatty acids (VLCFAs) in various tissues, including the nervous system. While there is currently no cure for AMN, management strategies focus on symptom relief and supportive care, including hormone replacement therapy and physical therapy. Early detection through genetic testing and symptom monitoring is crucial for optimizing treatment outcomes and quality of life for affected individuals. | ATP binding cassette subfamily D member 1 | |||
| 30 | Adult hepatocellular carcinoma Hepatoma | 782,000 new cases annually, with over 746,000 deaths attributed to the disease each year | TSC1;EGF;CASP8;CTNNB1;PDGFRL;PIK3CA;TSC2;AXIN1;TP53 | TSC1: Tuberous sclerosis 1 Hamartin KIAA0243 EGF: Epidermal growth factor CASP8: Caspase 8 FLICE (FADD-like interleukin-1beta-converting enzyme) FLICE1 CTNNB1: Catenin beta-1 Beta-catenin CTNNB PDGFRL: Platelet-derived growth factor receptor-like protein MGC142159 PGR15 PIK3CA: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform p110α TSC2: Tuberous sclerosis 2 Tuberin AXIN1: Axis inhibition protein 1 Conductin AXIN PPP1R49 TP53: Tumor protein p53 p53 Transformation-related protein 53 Antigen NY-CO-13 | Adult hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, typically arising from hepatocytes, the main cell type in the liver. It is strongly associated with chronic liver diseases, notably cirrhosis caused by viral hepatitis (B and C), alcohol abuse, non-alcoholic fatty liver disease (NAFLD), and aflatoxin exposure. Symptoms often manifest in later stages, including abdominal pain, weight loss, jaundice, and hepatomegaly. Diagnosis involves imaging studies like ultrasound, CT scans, and MRI, along with serum biomarkers such as alpha-fetoprotein (AFP). Treatment options depend on the stage of the cancer and may include surgical resection, liver transplantation, ablation therapy, transarterial chemoembolization (TACE), systemic chemotherapy, or targeted therapies such as sorafenib. Prognosis varies widely based on tumor stage, underlying liver function, and treatment response, with early detection significantly improving outcomes. | TSC complex subunit 1;epidermal growth factor;caspase 8;catenin beta 1;platelet derived growth factor receptor like;phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha;TSC complex subunit 2;axin 1;tumor protein p53 | |||
| 31 | Adult polyglucosan body disease | approximately 1 in 100,000 individuals | GBE1 | GBE 1,4-alpha-glucan-branching enzyme Amylo-(1,4 to 1,6) transglycosylase Branching enzyme 1 Glycogen Branching Enzyme | Adult polyglucosan body disease (APBD) is a rare neurodegenerative disorder characterized by the accumulation of polyglucosan bodies in the central and peripheral nervous systems. It typically manifests in adulthood, with symptoms including progressive weakness and stiffness in the legs, urinary urgency and incontinence, and sensory loss. Cognitive impairment may also occur in some cases. APBD is caused by mutations in the GBE1 gene, resulting in deficiency of the glycogen branching enzyme. This leads to the abnormal accumulation of glycogen in nerve cells, disrupting their function. Diagnosis often involves genetic testing and nerve biopsies, while management focuses on symptom relief and supportive care, as there is currently no cure for the disease. | 1,4-alpha-glucan branching enzyme 1 | |||
| 32 | Adult-onset autosomal dominant leukodystrophy | less than 1 in 1,000,000 individuals | LMNB1 | LMN2 Lamin B1 Lamin-B1 | Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare genetic disorder characterized by progressive degeneration of the white matter in the central nervous system, typically manifesting in adulthood. It is caused by duplications of the LMNB1 gene, leading to overexpression of lamin B1, a structural protein in the nuclear envelope. Symptoms often begin with autonomic dysfunction, such as urinary and bowel incontinence, followed by motor and cognitive impairments, including muscle stiffness, spasticity, and ataxia. ADLD progresses gradually, and while there is currently no cure, management focuses on alleviating symptoms and improving quality of life through supportive therapies | lamin B1 | |||
| 33 | AHDC1-related intellectual disability-obstructive sleep apnea-mild dysmorphism syndrome | fewer than 100 cases have been documented worldwide | AHDC1 | KIAA0529 AT-Hook DNA Binding Motif Containing 1 | AHDC1-related intellectual disability-obstructive sleep apnea-mild dysmorphism syndrome is a rare genetic disorder caused by mutations in the AHDC1 gene. This syndrome is characterized by intellectual disability, developmental delays, and distinctive facial features, which may include a broad forehead, wide-set eyes, and a flat nasal bridge. Affected individuals often experience obstructive sleep apnea due to craniofacial abnormalities and hypotonia. Additional features may include poor muscle tone, speech delays, and behavioral issues. Diagnosis is typically confirmed through genetic testing, and management focuses on addressing the individual symptoms, such as providing educational support, treating sleep apnea, and managing any other associated medical conditions. | AT-hook DNA binding motif containing 1 | |||
| 34 | Aicardi-Goutières syndrome | approximately 1 in 100,000 to 1 in 1,000,000 individuals globally | ADAR;TREX1;RNASEH2B;RNASEH2C;SAMHD1;RNASEH2A;IFIH1 | ADAR (Adenosine Deaminase, RNA-Specific) Alias: ADAR1 TREX1 (Three Prime Repair Exonuclease 1) Alias: DNT1, TREX1L, AGS1, Aicardi-Goutieres syndrome 1 protein RNASEH2B (Ribonuclease H2 Subunit B) Alias: RNase H(35 kD) subunit B, RNASEH35B, Aicardi-Goutieres syndrome 2 protein RNASEH2C (Ribonuclease H2 Subunit C) Alias: RNase H(30 kD) subunit C, RNASEH30C SAMHD1 (SAM And HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1) Alias: SAMHD1, Aicardi-Goutieres syndrome 5 protein RNASEH2A (Ribonuclease H2 Subunit A) Alias: RNase H(49 kD) subunit A, RNASEH49A IFIH1 (Interferon Induced with Helicase C Domain 1) Alias: MDA5, Helicard, Melanoma Differentiation-Associated protein 5 | Aicardi-Goutières syndrome (AGS) is a rare genetic disorder that predominantly affects the brain and skin, often presenting with symptoms similar to congenital viral infections. Typically manifesting in infancy or early childhood, AGS is characterized by progressive encephalopathy, leading to severe intellectual and physical disabilities. Patients may exhibit symptoms such as irritability, feeding difficulties, developmental regression, and spasticity. Other notable features include chronic cerebrospinal fluid lymphocytosis, intracranial calcifications, and elevated interferon-alpha levels. Mutations in any of several genes, including TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1, can cause AGS, and it is inherited in an autosomal recessive or, in rare cases, autosomal dominant manner. There is no cure, and treatment focuses on managing symptoms and supportive care. | adenosine deaminase RNA specific;three prime repair exonuclease 1;ribonuclease H2 subunit B;ribonuclease H2 subunit C;SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1;ribonuclease H2 subunit A;interferon induced with helicase C domain 1 | |||
| 35 | ALG1-CDG | only a few dozen cases reported worldwide | ALG1 | ALG1, Chitobiosyldiphosphodolichol Beta-Mannosyltransferase CDG1K (Congenital disorder of glycosylation, type Ik) DPMS (Dolichyl-phosphate beta-D-mannosyltransferase) GPT14 (Glycosylphosphatidylinositol-anchored protein 14) MRT5 (Mannosyltransferase 5) ALG1, Chitobiosyldiphosphodolichol Beta-Mannosyltransferase Homolog (S. Cerevisiae) | ALG1-CDG, or ALG1 congenital disorder of glycosylation, is a rare genetic disorder characterized by deficiencies in the ALG1 gene, which is responsible for producing an enzyme involved in the process of protein glycosylation. This deficiency leads to abnormalities in glycoprotein synthesis, impacting various bodily functions. Individuals with ALG1-CDG may experience a range of symptoms, including developmental delay, intellectual disability, seizures, liver dysfunction, and abnormalities in facial features. The severity of the condition can vary widely among affected individuals, with some experiencing life-threatening complications. Management typically involves supportive care and may include therapies aimed at addressing specific symptoms. Early diagnosis through genetic testing is crucial for implementing appropriate interventions and improving outcomes for affected individuals. | ALG1 chitobiosyldiphosphodolichol beta-mannosyltransferase | HeLa - Human cervical cancer cells. A549 - Human lung carcinoma cells. PC-3 - Human prostate cancer cells. NIH 3T3 - Mouse fibroblast cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. | ||
| 36 | ALG9-CDG | approximately 1 in 20,000 to 1 in 100,000 live births | ALG9 | DPMS2 MRT11 ALG9, alpha-1,2-mannosyltransferase Alpha-1,2-mannosyltransferase ALG9 | ALG9-CDG, also known as congenital disorder of glycosylation (CDG) caused by mutations in the ALG9 gene, is a rare genetic disorder affecting the process of protein glycosylation. ALG9 encodes an enzyme involved in the early steps of N-linked glycosylation, a crucial process for proper protein folding and function. Defects in ALG9 lead to impaired glycosylation, resulting in a spectrum of clinical manifestations including developmental delay, intellectual disability, seizures, growth retardation, and various organ dysfunctions. Symptoms can vary widely in severity, and diagnosis often involves genetic testing and biochemical analysis of glycosylation patterns. Management typically focuses on supportive care and may include physical and occupational therapy, dietary modifications, and treatment of specific symptoms. | ALG9 alpha-1,2-mannosyltransferase | |||
| 37 | Alopecia universalis | 1 in 100,000 individuals | HR | BRCA1 (Breast Cancer Type 1 Susceptibility Protein) BRCA2 (Breast Cancer Type 2 Susceptibility Protein) RAD51 (RAD51 Recombinase) RAD52 (RAD52 Homolog, DNA Repair Protein) RAD54 (RAD54 Homolog, DNA Repair Protein) RAD51C (RAD51 Paralog C) RAD51D (RAD51 Paralog D) RAD51B (RAD51 Paralog B) RAD51AP1 (RAD51 Associated Protein 1) PALB2 (Partner and Localizer of BRCA2) XRCC2 (X-ray Repair Cross Complementing 2) XRCC3 (X-ray Repair Cross Complementing 3) | Alopecia universalis is a severe form of alopecia areata, an autoimmune disorder characterized by sudden and complete hair loss across the entire body, including the scalp, eyebrows, eyelashes, and body hair. Unlike alopecia areata, which typically presents with patchy hair loss, alopecia universalis results in the total absence of hair, leaving the affected individual completely bald. This condition is thought to occur when the immune system mistakenly targets hair follicles, leading to their destruction and subsequent hair loss. Alopecia universalis can have a significant impact on a person's physical appearance and emotional well-being, as it can cause distress and impact self-esteem. Treatment options for alopecia universalis are limited, and while some individuals may experience spontaneous hair regrowth, others may require ongoing management with therapies such as corticosteroids, immunosuppressants, or topical treatments to help stimulate hair regrowth. | HR lysine demethylase and nuclear receptor corepressor | NIH 3T3 - Mouse fibroblast cells. HeLa - Human cervical cancer cells. HEK293 - Human embryonic kidney cells. | ||
| 38 | Alopecia-intellectual disability syndrome | only a few reported cases worldwide | LSS;AHSG;ITGB6 | LSS (Lanosterol Synthase) Alias: LPC, CYP51 AHSG (Alpha-2-HS-Glycoprotein) Alias: Fetuin-A, FETUA, Alpha-2-Z-globulin, Gp-40, BFGF-R3 ITGB6 (Integrin Subunit Beta 6) Alias: Integrin beta-6, CD49f, ITGbeta6 | Alopecia-intellectual disability syndrome, also known as Marie Unna hereditary hypotrichosis, is a rare genetic disorder characterized by early-onset hair loss (alopecia) and intellectual disability. This syndrome typically presents with sparse or absent scalp hair, as well as abnormalities in hair growth on other parts of the body. Alongside alopecia, individuals with this condition often exhibit developmental delays, intellectual disability, and in some cases, additional physical abnormalities. The syndrome is inherited in an autosomal recessive pattern, meaning both copies of the responsible gene must be mutated for the condition to manifest. Treatment primarily focuses on managing symptoms and providing support for developmental and intellectual challenges. | lanosterol synthase;alpha 2-HS glycoprotein;integrin subunit beta 6 | NIH 3T3 - Mouse fibroblast cells. HeLa - Human cervical cancer cells. HEK293 - Human embryonic kidney cells. PC-3 - Human prostate cancer cells. | ||
| 39 | Alpers-Huttenlocher syndrome | 1 in 100,000 to 1 in 250,000 individuals affected | POLG | POLG1: This is the main isoform of the POLG gene. MTPOLG: Mitochondrial DNA-directed DNA polymerase gamma. POLGA: Polymerase (DNA directed), gamma, A. | Alpers-Huttenlocher syndrome (AHS) is a rare and severe neurological disorder primarily affecting infants and young children. It is characterized by a triad of symptoms including intractable seizures, developmental regression, and liver dysfunction. The syndrome is typically caused by mutations in the POLG gene, which encodes a mitochondrial DNA polymerase involved in replication and repair processes. As a result, affected individuals experience progressive neurological deterioration, leading to profound developmental delays and often early mortality. The liver dysfunction observed in AHS can manifest as hepatomegaly, liver failure, or elevated liver enzymes. Early diagnosis and management are crucial, although treatment options remain limited, focusing primarily on supportive care and symptom management. | DNA polymerase gamma, catalytic subunit | |||
| 40 | Alpha-thalassemia-X-linked intellectual disability syndrome | fewer than 1 in 100,000 individuals affected worldwide | ATRX | ATRX XH2 XNP Alpha Thalassemia/Mental Retardation Syndrome X-Linked | Alpha-thalassemia-X-linked intellectual disability (ATR-X) syndrome is a rare genetic disorder characterized by a combination of intellectual disability, distinctive facial features, and alpha-thalassemia, a blood disorder involving reduced production of hemoglobin. Individuals with ATR-X syndrome typically exhibit developmental delays, speech difficulties, and various physical abnormalities such as skeletal anomalies and genital abnormalities in males. This X-linked condition is caused by mutations in the ATRX gene, which plays a critical role in chromatin remodeling and gene expression regulation. The severity of symptoms can vary widely among affected individuals, and management primarily focuses on supportive care and addressing specific symptoms associated with the syndrome. | ATRX chromatin remodeler | |||
| 41 | Alternating hemiplegia of childhood | 1 in 1 million individuals | ATP1A2;CACNA1A;SLC1A3;ATP1A3 | ATP1A2 (ATPase Na+/K+ Transporting Subunit Alpha 2) Alias: FHM2, ATP1B, MHP2, NA+/K+ ATPase subunit alpha-2, Sodium/potassium-transporting ATPase alpha-2 chain CACNA1A (Calcium Voltage-Gated Channel Subunit Alpha1 A) Alias: CACNL1A4, CAV2.1, FHM, SCA6, CACNL1A4R, CACNL1A4S, CACNL1A4L, CACNL1A4B, CACNL1A4D, CACNL1A4F, CACNL1A4H, CACNL1A4T, CACNL1A4V, CACNL1A4X, CACNL1A4Y, CACNL1A4Z, Voltage-gated calcium channel subunit alpha Cav2.1 SLC1A3 (Solute Carrier Family 1 Member 3) Alias: EAAT1, GLAST, Excitatory amino acid transporter 1, Solute carrier family 1 member 3 ATP1A3 (ATPase Na+/K+ Transporting Subunit Alpha 3) Alias: ATPase alpha 3, ATP1B, ATP1A3L, ATPase Na+/K+ transporting subunit alpha-3 | Alternating hemiplegia of childhood (AHC) is a rare neurological disorder characterized by recurrent episodes of paralysis that typically affect one side of the body or the other, or both sides simultaneously. These episodes can occur spontaneously or be triggered by various factors such as physical activity, stress, or excitement. In addition to hemiplegia, individuals with AHC may experience other symptoms including dystonia, choreoathetosis, and cognitive impairment. The condition usually begins in infancy or early childhood and tends to persist throughout life, although the severity and frequency of episodes may vary. AHC is often caused by mutations in the ATP1A3 gene, which encodes a protein involved in the regulation of ion transport in nerve cells. Treatment options are limited and primarily focus on managing symptoms and improving quality of life for affected individuals. | ATPase Na+/K+ transporting subunit alpha 2;calcium voltage-gated channel subunit alpha1 A;solute carrier family 1 member 3;ATPase Na+/K+ transporting subunit alpha 3 | |||
| 42 | Alveolar rhabdomyosarcoma | 1 case per 1 million children and adolescents | TP53;FOXO1;PAX7;PAX3;NF1 | TP53 (Tumor Protein P53) Alias: p53, Cellular tumor antigen p53, Phosphoprotein p53, Tumor suppressor p53 FOXO1 (Forkhead Box O1) Alias: FKHR, Forkhead in rhabdomyosarcoma, Forkhead box protein O1, Forkhead box protein O1A, FOXO1A PAX7 (Paired Box 7) Alias: HUP1, PAX7c, PAX7e, PAX7f, PAX7h PAX3 (Paired Box 3) Alias: HUP2, WS1, Pax-3, WS, WS1S NF1 (Neurofibromin 1) Alias: Neurofibromin, Neurofibromatosis type I, NF-I, Von Recklinghausen disease, NFNS, VRNF | Alveolar rhabdomyosarcoma (ARMS) is a rare and aggressive type of cancer that primarily affects children and young adults. It arises from skeletal muscle cells and typically manifests as a rapidly growing tumor, most commonly found in the extremities, trunk, or genitourinary region. ARMS is characterized by its small round blue cell morphology under the microscope, with genetic abnormalities often involving the fusion of the PAX3 or PAX7 gene with the FOXO1 gene. Despite advancements in treatment, including chemotherapy, radiation therapy, and surgery, the prognosis for ARMS remains challenging, with a significant risk of metastasis and recurrence. Early detection and multidisciplinary management are essential for improving outcomes in patients with this aggressive malignancy. | tumor protein p53;forkhead box O1;paired box 7;paired box 3;neurofibromin 1 | |||
| 43 | Amelocerebrohypohidrotic syndrome | few dozen cases reported worldwide | SLC13A5;ROGDI | SLC13A5 (Solute Carrier Family 13 Member 5) Alias: NaCT (Sodium-coupled citrate transporter), INDY (I'm not dead yet), C6orf91 ROGDI (ROGD domain-containing protein I) Alias: KIAA1161 | Amelocerebrohypohidrotic syndrome (ACHS), also known as Kohlschütter-Tönz syndrome, is a rare genetic disorder characterized by a combination of dental abnormalities, neurological impairments, and reduced ability to sweat. Individuals with ACHS typically present with early-onset, severe developmental delay, intellectual disability, and epilepsy. Dental anomalies, such as thin enamel, small or absent teeth, and dental caries, are prominent features of the syndrome. Additionally, affected individuals may exhibit hypohidrosis or anhidrosis, leading to impaired thermoregulation and an increased risk of overheating. ACHS is inherited in an autosomal recessive manner and is caused by mutations in the FAM20A gene. Management of ACHS involves multidisciplinary care focusing on addressing developmental, neurological, and dental needs, along with strategies to manage heat intolerance. | solute carrier family 13 member 5;rogdi atypical leucine zipper | N2A (Neuro-2a) - Mouse neuroblastoma cells. PC12 - Rat pheochromocytoma cells. NIH 3T3 - Mouse fibroblast cells. | ||
| 44 | Amyotrophic lateral sclerosis | 4 to 6 cases per 100,000 people in most populations | TREM2;UNC13A;CHMP2B;GLT8D1;DAO;DCTN1;EPHA4;ERBB4;FUS;GLE1;ANG;HNRNPA1;ANXA11;MATR3;NEFH;NEK1;PFN1;PON1;PON2;PON3;PPARGC1A;PRPH;ATXN2;SOD1;SQSTM1;TAF15;TARDBP;TBK1;UBQLN2;CFAP410;VAPB;VCP;CHCHD10;CCNF;FIG4;OPTN | TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) Alias: TREM-2, Trem2a UNC13A (Unc-13 Homolog A) Alias: Munc13-1 CHMP2B (Charged Multivesicular Body Protein 2B) Alias: Chromatin Modifying Protein 2B, Vacuolar Protein Sorting 2B GLT8D1 (Glycosyltransferase 8 Domain Containing 1) Alias: GLT8D1 DAO (D-Amino Acid Oxidase) Alias: D-amino-acid oxidase DCTN1 (Dynactin Subunit 1) Alias: Dynactin 1 EPHA4 (EPH Receptor A4) Alias: EPH-A4 ERBB4 (Erb-B2 Receptor Tyrosine Kinase 4) Alias: Her4, Tyrosine kinase-type cell surface receptor HER4, Proto-oncogene c-ErbB-4 FUS (Fused in Sarcoma) Alias: TLS, hnRNP P2, Translocated in Liposarcoma GLE1 (GLE1 RNA Export Mediator) Alias: GLE1L ANG (Angiogenin) Alias: Angiogenin, Ribonuclease 5 HNRNPA1 (Heterogeneous Nuclear Ribonucleoprotein A1) Alias: hnRNP A1, Ribonucleoprotein A1 ANXA11 (Annexin A11) Alias: Annexin XI, Annexin-11 MATR3 (Matrin 3) Alias: Matrin-3, Neuroblastoma-specific antigen NB NEFH (Neurofilament Heavy) Alias: NFH, NEF3, Neurofilament triplet H protein NEK1 (NIMA Related Kinase 1) Alias: NIMA-related kinase 1, NimA-related protein kinase 1 PFN1 (Profilin 1) Alias: Profilin-1 PON1 (Paraoxonase 1) Alias: Serum paraoxonase/arylesterase 1, Aromatic esterase 1 PON2 (Paraoxonase 2) Alias: Serum paraoxonase/arylesterase 2, Aromatic esterase 2 PON3 (Paraoxonase 3) Alias: Serum paraoxonase/arylesterase 3, Aromatic esterase 3 PPARGC1A (PPARG Coactivator 1 Alpha) Alias: PGC-1alpha, PPAR-gamma coactivator 1-alpha PRPH (Peripherin) Alias: Peripherin ATXN2 (Ataxin 2) Alias: Spinocerebellar ataxia type 2 protein, Spinocerebellar ataxia type 2 protein SOD1 (Superoxide Dismutase 1) Alias: Cu-Zn superoxide dismutase, Superoxide dismutase [Cu-Zn] SQSTM1 (Sequestosome 1) Alias: p62, Ubiquitin-binding protein p62 TAF15 (TATA-Box Binding Protein Associated Factor 2N) Alias: TAF2N, RBP56 TARDBP (TAR DNA Binding Protein) Alias: TDP-43, TAR DNA-binding protein 43 TBK1 (TANK Binding Kinase 1) Alias: NF-kappa-B-activating kinase, T2K UBQLN2 (Ubiquilin 2) Alias: UBQLN2, Ubiquitin-like protein 2 CFAP410 (Cilia And Flagella Associated Protein 410) Alias: CFAP410 VAPB (VAMP Associated Protein B And C) Alias: VAP-B, VAP-B/C VCP (Valosin Containing Protein) Alias: p97, Transitional endoplasmic reticulum ATPase CHCHD10 (Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10) Alias: MICOS complex subunit Mic25, Coiled-coil-helix-coiled-coil-helix domain-containing protein 10 CCNF (Cyclin F) Alias: FBXO1, Cyclin-F FIG4 (FIG4 Phosphoinositide 5-Phosphatase) Alias: Sac3, Sac domain-containing protein 3 OPTN (Optineurin) Alias: GLC1E, FIP2 | Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive neurodegenerative disorder characterized by the gradual degeneration and loss of motor neurons in the brain and spinal cord. This leads to muscle weakness, paralysis, and ultimately, respiratory failure, typically within 2 to 5 years of symptom onset. While the exact cause of ALS remains unclear, it is believed to involve a combination of genetic and environmental factors. There is currently no cure for ALS, and treatment primarily focuses on managing symptoms and improving quality of life through medication, therapy, and supportive care. | triggering receptor expressed on myeloid cells 2;unc-13 homolog A;charged multivesicular body protein 2B;glycosyltransferase 8 domain containing 1;D-amino acid oxidase;dynactin subunit 1;EPH receptor A4;erb-b2 receptor tyrosine kinase 4;FUS RNA binding protein;GLE1 RNA export mediator;angiogenin;heterogeneous nuclear ribonucleoprotein A1;annexin A11;matrin 3;neurofilament heavy chain;NIMA related kinase 1;profilin 1;paraoxonase 1;paraoxonase 2;paraoxonase 3;PPARG coactivator 1 alpha;peripherin;ataxin 2;superoxide dismutase 1;sequestosome 1;TATA-box binding protein associated factor 15;TAR DNA binding protein;TANK binding kinase 1;ubiquilin 2;cilia and flagella associated protein 410;VAMP associated protein B and C;valosin containing protein;coiled-coil-helix-coiled-coil-helix domain containing 10;cyclin F;FIG4 phosphoinositide 5-phosphatase;optineurin | N2A (Neuro-2a) - Mouse neuroblastoma cells. NIH 3T3 - Mouse fibroblast cells. HEK293 - Human embryonic kidney cells. COS-7 - Monkey kidney fibroblast cells. | ||
| 45 | Anaplastic oligodendroglioma | approximately 2-5% of all gliomas, which are tumors that arise from glial cells in the brain. Anaplastic oligodendrogliomas are more commonly diagnosed in adults, typically between the ages of 30 and 50 years old | IDH2;POT1 | IDH2 (Isocitrate Dehydrogenase [NADP(+)] 2, Mitochondrial) Alias: IDP, IDP-2, IDH, IDHM, IDP-2, ICD-M, IDP-B, IDH2A, mNADP-IDH, R155H, R172G, R172S, R172K, R172M POT1 (Protection of Telomeres 1) Alias: TINF2, TP2, TPP1, POT1-TPP1, TINT1, PT1, THW, POT1-TPP1 alpha-beta complex, hPot1 | Anaplastic oligodendroglioma is a type of malignant brain tumor that arises from oligodendrocytes, the cells responsible for producing the myelin sheath around nerve fibers in the brain. It is characterized by aggressive growth and infiltration into surrounding brain tissue. Anaplastic oligodendrogliomas are typically high-grade tumors, exhibiting cellular atypia and increased mitotic activity. They often present with symptoms such as seizures, headaches, and neurological deficits, depending on their location within the brain. Treatment typically involves a combination of surgical resection, radiation therapy, and chemotherapy, with prognosis varying depending on factors such as tumor grade, extent of surgical resection, and molecular characteristics. | isocitrate dehydrogenase (NADP(+)) 2;protection of telomeres 1 | HeLa - Human cervical cancer cells. A549 - Human lung carcinoma cells. PC-3 - Human prostate cancer cells. NIH 3T3 - Mouse fibroblast cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. | ||
| 46 | Aneurysm-osteoarthritis syndrome | less than 1 in 100,000 individuals | SMAD3 | less than 1 in 100,000 individuals | Aneurysm-osteoarthritis syndrome (AOS) is a rare genetic disorder characterized by the presence of arterial aneurysms and early-onset osteoarthritis. It is primarily caused by mutations in the SMAD3 gene, leading to abnormalities in the connective tissue. Individuals with AOS often present with arterial dilations, particularly affecting the aorta and other major arteries, which can predispose them to potentially life-threatening complications such as dissection or rupture. Additionally, patients commonly experience symptoms of osteoarthritis at a young age, affecting multiple joints and leading to pain and mobility issues. Early diagnosis and management are crucial to mitigate the risk of cardiovascular events and to address the musculoskeletal manifestations of the syndrome. | SMAD family member 3 | |||
| 47 | Aortic aneurysm, familial thoracic 4 | 1 in 5,000 to 10,000 individuals | MYH11 | SMHC (Smooth Muscle Myosin Heavy Chain) SMMHC (Smooth Muscle Myosin Heavy Chain) SMHH (Smooth Muscle Heavy Chain Myosin) MYHBC (Myosin Heavy Chain, Smooth Muscle, B isoform) SMC-2 (Smooth Muscle Myosin Heavy Chain 2) | Familial thoracic aortic aneurysm and dissection (FTAAD) type 4 is a genetic disorder characterized by the weakening of the aortic wall, leading to the formation of an aneurysm. Specifically, FTAAD4 is associated with mutations in the MYH11 gene, which encodes a protein important for the structure and function of smooth muscle cells in the aortic wall. This condition predisposes individuals to the development of thoracic aortic aneurysms, which can lead to life-threatening complications such as aortic dissection or rupture. FTAAD4 typically exhibits an autosomal dominant pattern of inheritance, meaning that individuals with a single copy of the mutated gene have an increased risk of developing the condition. Early detection through genetic testing and regular monitoring of aortic health are essential for managing FTAAD4 and reducing the risk of potentially catastrophic complications. | myosin heavy chain 11 | |||
| 48 | Aplasia cutis congenita | 1 in 10,000 births | PLEC;DLL4;ITGB4;BMS1 | PLEC (Plectin) Alias: HD1, BPAG1, Hemidesmosomal protein 1, Epidermolysis bullosa simplex with pyloric atresia protein DLL4 (Delta-like 4) Alias: Delta4, Delta-like ligand 4, Delta-like protein 4 ITGB4 (Integrin Subunit Beta 4) Alias: CD104, ITGB4B, Integrin beta-4 BMS1 (BMS1 Ribosome Biogenesis Factor) Alias: HSPC117, rRNA processing protein BMS1 homolog | Aplasia cutis congenita (ACC) is a rare congenital disorder characterized by the absence of skin, typically at birth. It can occur anywhere on the body but most commonly affects the scalp. ACC lesions can vary in size and depth, ranging from small, shallow areas of missing skin to larger defects involving underlying tissue, such as the skull. The exact cause is often unknown, though it can be associated with genetic factors, vascular abnormalities, or teratogenic exposures during pregnancy. Treatment depends on the severity and location of the lesions and may involve conservative management, surgical repair, or skin grafting. | plectin;delta like canonical Notch ligand 4;integrin subunit beta 4;BMS1 ribosome biogenesis factor | |||
| 49 | Aromatic L-amino acid decarboxylase deficiency | fewer than 1 in 1 million individuals worldwide | DDC | AADC (Aromatic L-Amino Acid Decarboxylase) DDC (Dopa Decarboxylase) DDC DOPA Decarboxylase Aromatic-L-amino-acid decarboxylase | Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder impairing neurotransmitter production in the brain. Symptoms, appearing in infancy, include developmental delay, movement disorders, and autonomic dysfunction. Diagnosis involves genetic testing and neurotransmitter metabolite analysis. Treatment focuses on symptom management with dopamine agonists and serotonin precursors, while gene therapy is being explored. | dopa decarboxylase | |||
| 50 | Arterial tortuosity syndrome | less than 1 in 1 million individuals | SLC2A10 | GLUT10 GLU10 Facilitative glucose transporter member 10 ATG | Arterial Tortuosity Syndrome (ATS) is a rare genetic disorder characterized by the abnormal twisting and lengthening (tortuosity) of the arteries throughout the body. This can lead to various cardiovascular complications, such as aneurysms, stenosis, and increased risk of arterial rupture. ATS is caused by mutations in the SLC2A10 gene, which is inherited in an autosomal recessive pattern. Common symptoms include elongated facial features, hyperextensible skin, joint hypermobility, and respiratory issues due to vascular abnormalities. Early diagnosis and regular monitoring are crucial for managing cardiovascular risks associated with ATS. | solute carrier family 2 member 10 | |||
| 51 | Aspartylglucosaminuria | approximately 1 in 1,000,000 globally | AGA | Aspartylglucosaminase AGA1 Aspartylglucosaminidase precursor | Aspartylglucosaminuria (AGU) is a rare autosomal recessive lysosomal storage disorder caused by mutations in the AGA gene, leading to a deficiency of the enzyme aspartylglucosaminidase. This enzyme deficiency results in the accumulation of glycoasparagines in tissues, causing progressive developmental delay, intellectual disability, coarse facial features, skeletal abnormalities, and a decline in motor and speech skills. Behavioral issues and psychiatric symptoms may also occur. Diagnosis is confirmed through genetic testing and enzyme assays, and while there is no cure, supportive treatments can help manage the symptoms. | aspartylglucosaminidase | |||
| 52 | Ataxia-hypogonadism-choroidal dystrophy syndrome | less than 1 in 1,000,000 individuals | PNPLA6 | Neuropathy Target Esterase (NTE) NEU NTE-related esterase Phospholipase B-like 3 Patatin-like phospholipase domain-containing protein 6 | Ataxia-hypogonadism-choroidal dystrophy syndrome, also known as Woods syndrome, is a rare genetic disorder characterized by a triad of symptoms: progressive ataxia leading to coordination and balance issues, hypogonadism resulting in underdeveloped reproductive organs and impaired fertility, and choroidal dystrophy causing vision impairment. This syndrome follows an autosomal recessive pattern of inheritance and is caused by mutations in the PNPLA6 gene, which encodes an enzyme involved in lipid metabolism and other cellular processes. Due to its rarity and complex symptomatology, diagnosis and management often require a multidisciplinary approach involving neurologists, endocrinologists, ophthalmologists, and genetic counselors. | patatin like phospholipase domain containing 6 | |||
| 53 | Atrial septal defect, ostium primum type | 1 in 1,500 live births | TLL1 | TLL dJ840G16.1 tolloid-like protein 1 TM27 | An atrial septal defect (ASD), ostium primum type, is a congenital heart defect characterized by an opening in the lower part of the atrial septum, near the atrioventricular valves. This type of ASD is associated with defects in the endocardial cushion and often occurs in conjunction with other abnormalities, such as cleft mitral valves or ventricular septal defects. Symptoms can range from none to significant, including breathlessness, fatigue, and palpitations, depending on the size of the defect and associated complications. Treatment typically involves surgical correction to close the defect and repair any associated anomalies. | tolloid like 1 | |||
| 54 | Atypical Rett syndrome | 1 in 10,000 to 1 in 15,000 live births | MECP2;CDKL5;GABBR2;NTNG1;SMC1A | MECP2 (Methyl-CpG Binding Protein 2) Alias: RTT, RS, MRX16, MRX79, PPMX, Rett Syndrome CDKL5 (Cyclin Dependent Kinase Like 5) Alias: STK9, Serine/Threonine Kinase 9, Epileptic Encephalopathy, Early Infantile, 2 GABBR2 (Gamma-Aminobutyric Acid Type B Receptor Subunit 2) Alias: GPR51, GABABR2 NTNG1 (Netrin G1) Alias: Netrin-G1, LRRC4C SMC1A (Structural Maintenance of Chromosomes 1A) Alias: SMC1, SMC1L1 | Atypical Rett syndrome is a neurodevelopmental disorder that shares some characteristics with classic Rett syndrome but varies in its clinical presentation. Unlike classic Rett syndrome, which primarily affects females and is caused by mutations in the MECP2 gene, atypical Rett syndrome may have different genetic causes, such as mutations in the CDKL5 or FOXG1 genes. Symptoms include developmental delays, intellectual disability, motor abnormalities, and sometimes seizures. The onset and severity of symptoms can be highly variable, leading to its classification into various subtypes. Diagnosis is based on clinical criteria and genetic testing. | methyl-CpG binding protein 2;cyclin dependent kinase like 5;gamma-aminobutyric acid type B receptor subunit 2;netrin G1;structural maintenance of chromosomes 1A | |||
| 55 | Auriculocondylar syndrome | fewer than 1 in 1,000,000 individuals | EDN1;GNAI3;PLCB4 | EDN1 (Endothelin 1) Alias: ET-1, PPET1, Preproendothelin-1 GNAI3 (G Protein Subunit Alpha I3) Alias: Gi3 alpha, Gi3A, GNAI3A, GNAI3B PLCB4 (Phospholipase C Beta 4) Alias: PLCB-ETA, Phosphoinositide phospholipase C-beta-4, PI-PLC | Auriculocondylar syndrome (ACS) is a rare genetic disorder characterized by facial and mandibular abnormalities such as micrognathia (small jaw), auricular anomalies (malformed external ears), facial asymmetry, and temporomandibular joint (TMJ) issues. It is typically inherited in an autosomal dominant pattern and linked to mutations in the PLCB4, GNAI3, or EDN1 genes. Management of ACS involves a multidisciplinary approach to address the specific symptoms and structural abnormalities present in affected individuals. | endothelin 1;G protein subunit alpha i3;phospholipase C beta 4 | |||
| 56 | Autosomal agammaglobulinemia | less than 1 in 1,000,000 individuals worldwide | PIK3R1;IGHM;TCF3;LRRC8A;IGLL1;CD79B;CD79A;BLNK | PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) Aliases: GRB1, p85-ALPHA, p85, p50-ALPHA, p55-ALPHA, p85α IGHM (Immunoglobulin Heavy Constant Mu) Aliases: IgM, IGM TCF3 (Transcription Factor 3) Aliases: E2A, ITF1, bHLHb21, VDIR LRRC8A (Leucine Rich Repeat Containing 8 VRAC Subunit A) Aliases: SWELL1, FRTL, LRR8A IGLL1 (Immunoglobulin Lambda Like Polypeptide 1) Aliases: 14.1, AGM1, IGO, VPREB2 CD79B (CD79b Molecule) Aliases: B29, IGB, AGM6 CD79A (CD79a Molecule) Aliases: MB-1, IGA, MB1 BLNK (B Cell Linker) Aliases: SLP65, BASH, BCA, BLS, SLP-65 | Autosomal agammaglobulinemia is a rare primary immunodeficiency disorder characterized by a marked reduction or absence of immunoglobulins (antibodies) in the blood. Unlike the more common X-linked agammaglobulinemia, this form is inherited in an autosomal recessive manner, meaning both copies of a gene must be mutated for the disease to manifest. Individuals with this condition have a severe reduction in B cells, which are crucial for producing antibodies. As a result, they are highly susceptible to recurrent bacterial infections starting in infancy or early childhood. Treatment often involves regular immunoglobulin replacement therapy to boost the immune system and prevent infections. | phosphoinositide-3-kinase regulatory subunit 1;immunoglobulin heavy constant mu;transcription factor 3;leucine rich repeat containing 8 VRAC subunit A;immunoglobulin lambda like polypeptide 1;CD79b molecule;CD79a molecule;B cell linker | PC-3 - Human prostate cancer cells. NIH 3T3 - Mouse fibroblast cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. | ||
| 57 | Autosomal dominant Alport syndrome | approximately 1 in 50,000 live births | COL4A3;COL4A4 | COL4A3 (Collagen Type IV Alpha 3 Chain) Alias: Arresten, Goodpasture Antigen, GP, GPBP, MGC92627 Database IDs: HGNC ID: 2204 NCBI Gene ID: 1285 Ensembl: ENSG00000169031 OMIM: 120070 COL4A4 (Collagen Type IV Alpha 4 Chain) Alias: Alport Syndrome, Autosomal Recessive, Alport Syndrome, Autosomal Dominant, AS, ATS, MGC125929 Database IDs: HGNC ID: 2206 NCBI Gene ID: 1286 Ensembl: ENSG00000197587 OMIM: 120131 | Autosomal dominant Alport syndrome (ADAS) is a genetic disorder characterized by progressive kidney disease, hearing loss, and eye abnormalities. It results from mutations in the COL4A3 or COL4A4 genes, which encode type IV collagen, a crucial component of the basement membranes in the kidneys, inner ear, and eyes. Unlike the more common X-linked Alport syndrome, ADAS affects both males and females similarly, though the severity can vary. Patients often experience hematuria (blood in urine) from a young age, with proteinuria and kidney function decline developing later in life. Early diagnosis and management are essential to mitigate progression to end-stage renal disease. | collagen type IV alpha 3 chain;collagen type IV alpha 4 chain | |||
| 58 | Autosomal dominant centronuclear myopathy | less than 1 in 1,000,000 individuals | RYR1;BIN1;MTMR14;MYF6;DNM2 | RYR1 (Ryanodine Receptor 1) Alias: RYR, MHS, MHS1, CCO, RYR-1 BIN1 (Bridging Integrator 1) Alias: AMPH2, ALP, SH3P9, MGC111040, MYC box-dependent-interacting protein 1 MTMR14 (Myotubularin Related Protein 14) Alias: Jumpy, KIAA0833, MTMRL MYF6 (Myogenic Factor 6) Alias: MRF4, HERF1, MYF-6, bHLHc4 DNM2 (Dynamin 2) Alias: CMT2M, CMTDI1, DYN2, LCCS5, DYNII | Autosomal dominant centronuclear myopathy (ADCNM) is a rare genetic disorder characterized by muscle weakness and wasting, particularly affecting the muscles closest to the center of the body, such as those in the neck, shoulders, and hips. This condition is caused by mutations in the DNM2 gene, which encodes dynamin-2, a protein involved in muscle cell structure and function. Symptoms typically appear in adolescence or early adulthood and can include difficulty walking, lifting, and other activities requiring muscle strength. The severity of the condition can vary, with some individuals experiencing mild symptoms and others having more significant muscle impairment | ryanodine receptor 1;bridging integrator 1;myotubularin related protein 14;myogenic factor 6;dynamin 2 | |||
| 59 | Autosomal dominant Charcot-Marie-Tooth disease type 2 with giant axons | approximately 1 in 25,000 to 1 in 40,000 individuals worldwide | DCAF8 | WDR42B (WD Repeat Domain 42B) DDB1 and CUL4 Associated Factor 8 WD Repeat-Containing Protein 42B | Autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2) with giant axons is a subtype of Charcot-Marie-Tooth (CMT) disease, a group of inherited peripheral neuropathies. In this specific subtype, individuals inherit a mutated gene from one parent, leading to the development of peripheral nerve damage. CMT2 with giant axons is characterized by the presence of abnormally enlarged axons in nerve biopsies, which can contribute to the clinical manifestations of the disease. Symptoms typically include muscle weakness and atrophy, sensory loss, and decreased reflexes, primarily affecting the feet and legs initially and progressing upwards over time. Genetic testing can confirm the diagnosis, with mutations in genes such as MFN2 and GDAP1 commonly associated with this subtype. Management often involves symptomatic treatment and physical therapy to improve muscle strength and function, as well as genetic counseling for affected individuals and their families. | DDB1 and CUL4 associated factor 8 | |||
| 60 | Autosomal dominant dopa-responsive dystonia | approximately 1 in 1 million individuals | IMPDH2;GCH1 | IMPDH2 (Inosine-5'-Monophosphate Dehydrogenase 2) Alias: IMPD2, IMD2 GCH1 (GTP Cyclohydrolase 1) Alias: DYT5, GCH, GTP-CH-I | Autosomal dominant dopa-responsive dystonia (DYT5a) is a rare genetic movement disorder characterized by involuntary muscle contractions, tremors, and abnormal postures. It typically begins in childhood or adolescence and is caused by mutations in the GCH1 gene, affecting dopamine production in the brain. Symptoms often respond well to low doses of levodopa, a precursor to dopamine, leading to significant improvement in motor function. Genetic testing is necessary for diagnosis, and treatment involves long-term management with levodopa therapy. Early detection and appropriate treatment can significantly improve quality of life for affected individuals. | inosine monophosphate dehydrogenase 2;GTP cyclohydrolase 1 | HEK293-Human embryonic kidney cells, HepG2-Human liver cancer cells Rat fibroblast cell lines (like L6), Rat liver cells SK-N-SH -Human neuroblastoma cells (SK-N-SH) hCMEC/D3 - Human brain endothelial cells PC12- Rat pheochromocytoma cells Rat brain microvascular endothelial cell | ||
| 61 | Autosomal dominant focal dystonia, DYT25 type | only a few reported cases worldwide | GNAL | Gαolf G alpha-olf | Autosomal dominant focal dystonia, specifically DYT25 type, is a rare genetic disorder characterized by involuntary muscle contractions leading to abnormal movements and postures, typically localized to specific body regions like the neck or hand. Caused by mutations in the GNAL gene, which disrupts normal basal ganglia function, symptoms usually emerge in adulthood and vary in severity. Treatment options include medications, botulinum toxin injections, or deep brain stimulation surgery, aiming to alleviate symptoms and improve quality of life for affected individuals. | G protein subunit alpha L | SH-SY5Y-Human neuroblastoma cells HEK293-Human embryonic kidney 293 (HEK293) cells Rat pheochromocytoma cells (PC12) Rat brain-derived cell lines, such as C6 glioma cells | ||
| 62 | Autosomal dominant generalized dystrophic epidermolysis bullosa | 1 in 50,000 to 1 in 100,000 live births | COL7A1 | Epidermolysis Bullosa Dystrophica EBD1 Collagen, Type VII, Alpha-1 | Autosomal dominant generalized dystrophic epidermolysis bullosa (AD-GDEB) is a rare genetic disorder characterized by fragile skin that easily blisters and tears in response to minor trauma. This condition is caused by mutations in the COL7A1 gene, which encodes type VII collagen, a crucial component of anchoring fibrils that secure the epidermis to the underlying dermis. Individuals with AD-GDEB typically present with widespread blistering at birth or early infancy, which can lead to scarring, milia (tiny white bumps), and nail dystrophy. Despite being a lifelong condition, the severity can vary widely among affected individuals. | collagen type VII alpha 1 chain | Human dermal fibroblasts Human keratinocytes Rat skin fibroblast cell lines (e.g., L929 cells) Rat epithelial cell lines (e.g., Rat2 cells) | ||
| 63 | Autosomal dominant generalized epidermolysis bullosa simplex, intermediate form | approximately 7 to 8 per million live births | KRT5;KRT14 | KRT5 (Keratin 5) Aliases: CK5 (Cytokeratin 5) K5 Keratin, type II cytoskeletal 5 Cytokeratin-5 KRT14 (Keratin 14) Aliases: CK14 (Cytokeratin 14) K14 Keratin, type I cytoskeletal 14 Cytokeratin-14 | Autosomal dominant generalized epidermolysis bullosa simplex, intermediate form, is a rare genetic disorder characterized by skin fragility leading to blistering and erosions, often triggered by minor trauma. The condition is caused by mutations in the KRT5 or KRT14 genes, which encode keratin proteins essential for skin integrity. Blistering typically appears at birth or in early infancy and may affect widespread areas of the body. While the condition is lifelong, its severity can vary, with some individuals experiencing milder symptoms over time. There is no cure, but management focuses on wound care, preventing infections, and minimizing trauma to the skin. | keratin 5;keratin 14 | MCF-7 - Human breast cancer cells. HEK293 - Human embryonic kidney cells. Kera - Human keratinocytes. | ||
| 64 | dominant generalized epidermolysis bullosa simplex, severe form | approximately 6-30 cases per 1 million live births | KRT5;KRT14 | KRT5 (Keratin 5) Aliases: CK5 (Cytokeratin 5) K5 Keratin, type II cytoskeletal 5 Cytokeratin-5 KRT14 (Keratin 14) Aliases: CK14 (Cytokeratin 14) K14 Keratin, type I cytoskeletal 14 Cytokeratin-14 | Autosomal dominant generalized epidermolysis bullosa simplex (AD-GEBS), severe form, is a genetic skin disorder characterized by fragile skin that blisters easily in response to minor trauma. It is caused by mutations in the KRT5 or KRT14 genes, which encode keratin proteins essential for skin integrity. Symptoms typically present at birth or in early infancy and include widespread blistering, erosions, and sometimes nail dystrophy. The severe form can lead to significant complications, including infections and impaired quality of life. The condition is inherited in an autosomal dominant pattern, meaning only one copy of the mutated gene is sufficient to cause the disorder. Treatment focuses on wound care, infection prevention, and pain management. | keratin 5;keratin 14 | HaCaT-Human keratinocytes Human epidermal stem cells RHEK1 Rat keratinocyte cell lines Rat skin fibroblast | ||
| 65 | Autosomal dominant hypohidrotic ectodermal dysplasia | approximately 1 in 100,000 live births | EDARADD;KDF1;EDAR;TRAF6 | " EDARADD (EDAR-Associated Death Domain) Alias: EDAR-associated death domain protein, EDARADD KDF1 (Keratinocyte Differentiation Factor 1) Alias: KDF1, Keratinocyte Differentiation Factor 1 EDAR (Ectodysplasin A Receptor) Alias: Ectodysplasin A receptor, EDAR TRAF6 (TNF Receptor Associated Factor 6) Alias: TNF receptor-associated factor 6, TRAF6" | Autosomal dominant hypohidrotic ectodermal dysplasia (AD-HED) is a genetic disorder characterized by abnormalities in structures derived from the ectoderm, such as hair, teeth, nails, and sweat glands. It's caused by mutations in the EDA gene, affecting its protein product, which plays a crucial role in the development of these ectodermal structures. Individuals with AD-HED typically present with sparse hair, missing or malformed teeth, reduced ability to sweat, and abnormal nails. The severity of symptoms can vary widely among affected individuals, even within the same family. Treatment focuses on managing symptoms and may include dental prosthetics, artificial sweat supplementation, and supportive care for associated health issues. | EDAR associated death domain;keratinocyte differentiation factor 1;ectodysplasin A receptor;TNF receptor associated factor 6 | HaCaT-Human keratinocytes Human dermal fibroblasts HEK293-Human epithelial cells L929-Rat skin fibroblasts Rat keratinocyte cell lines THP-1 -Human monocytic cells MG-63 -Human osteoblastic cells ROS 17/2.8-Rat osteoblast cell lines L6-Rat fibroblast cell lines | ||
| 66 | Autosomal dominant nocturnal frontal lobe epilepsy | 1 to 7 per 100,000 individuals | CHRNA2;CHRNA4;CHRNB2;CRH;CABP4;DEPDC5;KCNT1 | CHRNA2 (Cholinergic Receptor Nicotinic Alpha 2 Subunit) Alias: nAChRα2 CHRNA4 (Cholinergic Receptor Nicotinic Alpha 4 Subunit) Alias: nAChRα4 CHRNB2 (Cholinergic Receptor Nicotinic Beta 2 Subunit) Alias: nAChRβ2 CRH (Corticotropin Releasing Hormone) Alias: CRF, CRH-RF, CRH1 CABP4 (Calcium Binding Protein 4) Alias: CaBP4 DEPDC5 (DEP Domain Containing 5) Alias: KIAA1712 KCNT1 (Potassium Sodium-Activated Channel Subfamily T Member 1) Alias: SLACK, KCNT1, KNa1.1 | Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE) is a rare form of epilepsy characterized by seizures that predominantly occur during sleep. It is inherited in an autosomal dominant pattern, meaning a single copy of the mutated gene from one parent is sufficient to cause the disorder. ADNFLE typically manifests with sudden, brief, and often violent seizures, including motor movements, vocalizations, and sometimes complex behaviors. These seizures can be difficult to control with medication and may require specialized treatment approaches. Mutations in genes encoding neuronal nicotinic acetylcholine receptors, such as CHRNA4 and CHRNB2, have been associated with ADNFLE. Early recognition and proper management are crucial for individuals with this condition to achieve optimal outcomes. | cholinergic receptor nicotinic alpha 2 subunit;cholinergic receptor nicotinic alpha 4 subunit;cholinergic receptor nicotinic beta 2 subunit;corticotropin releasing hormone;calcium binding protein 4;DEP domain containing 5, GATOR1 subcomplex subunit;potassium sodium-activated channel subfamily T member 1 | Human neuroblastoma cells (e.g., SH-SY5Y cells) Human embryonic kidney 293 (HEK293) cells (often used for expression studies) Rat cell lines: Rat pheochromocytoma cells (PC12 cells) Rat brain-derived cell lines (e.g., C6 glioma cells) | ||
| 67 | Autosomal dominant non-syndromic intellectual disability | 1% of the global population is approximately 80 million people. 3% of the global population is approximately 240 million people. | PPP3CA;RAB11A;CAMK2A;CAMK2B;DEAF1;MED12L;ZMYND11;CDH15;TRPM3;KDM5B;ASH1L;CSNK2B;CUX1;KIRREL3;CLTC;MBD5;PRICKLE2;CHAMP1;DOCK8;DLL1;SET;BRSK2;SYNGAP1;TCF4;CACNA1I;CACNG2;CIC;SETD1B;TAOK1;DYNC1H1;EEF1A2;EPB41L1;ERBB4;GRIN1;GRIN2B;HIVEP2;ITSN1;KCNQ2;KCNQ5;MYT1L;NBEA;KIF1A | PPP3CA (Protein Phosphatase 3 Catalytic Subunit Alpha) Alias: CALNA, CALNA1, PP2BA RAB11A (RAB11A, Member RAS Oncogene Family) Alias: YL8, RAB11, RAB11A CAMK2A (Calcium/Calmodulin Dependent Protein Kinase II Alpha) Alias: CAMKA, CaMKII alpha CAMK2B (Calcium/Calmodulin Dependent Protein Kinase II Beta) Alias: CAMKB, CaMKII beta DEAF1 (Deformed Epidermal Autoregulatory Factor 1 Homolog) Alias: NUDR, SPN, DEAF-1 MED12L (Mediator Complex Subunit 12 Like) No common aliases ZMYND11 (Zinc Finger MYND-Type Containing 11) Alias: BS69, ZNF822 CDH15 (Cadherin 15) Alias: M-Cadherin, CDH14 TRPM3 (Transient Receptor Potential Cation Channel Subfamily M Member 3) Alias: LTRPC3 KDM5B (Lysine Demethylase 5B) Alias: JARID1B, PLU1, RBP2-H1 ASH1L (ASH1 Like Histone Lysine Methyltransferase) Alias: KMT2H CSNK2B (Casein Kinase 2 Beta) Alias: CK2B, G5A, CSK2B CUX1 (Cut Like Homeobox 1) Alias: CDP, CUTL1 KIRREL3 (Kin of IRRE Like 3) Alias: KIRREL2, NEPH2 CLTC (Clathrin Heavy Chain) Alias: CHC, CLH-22 MBD5 (Methyl-CpG Binding Domain Protein 5) Alias: RSTS1 PRICKLE2 (Prickle Planar Cell Polarity Protein 2) Alias: EPM5, RICKLE2 CHAMP1 (Chromosome Alignment Maintaining Phosphoprotein 1) No common aliases DOCK8 (Dedicator of Cytokinesis 8) Alias: ZIR8 DLL1 (Delta Like Canonical Notch Ligand 1) Alias: DELTA1, H-Delta-1 SET (SET Nuclear Proto-Oncogene) Alias: PHAPII, IGAAD BRSK2 (BR Serine/Threonine Kinase 2) Alias: SAD1B SYNGAP1 (Synaptic Ras GTPase Activating Protein 1) Alias: MRD5 TCF4 (Transcription Factor 4) Alias: E2-2, ITF2, SEF2-1 CACNA1I (Calcium Voltage-Gated Channel Subunit Alpha1 I) Alias: Cav3.3 CACNG2 (Calcium Voltage-Gated Channel Auxiliary Subunit Gamma 2) Alias: STARGAZIN CIC (Capicua Transcriptional Repressor) Alias: HMGIYC SETD1B (SET Domain Containing 1B) Alias: KMT2G TAOK1 (TAO Kinase 1) Alias: KIAA1361, PSK1 DYNC1H1 (Dynein Cytoplasmic 1 Heavy Chain 1) Alias: DHC1, DHC1A EEF1A2 (Eukaryotic Translation Elongation Factor 1 Alpha 2) Alias: EEF1AL EPB41L1 (Erythrocyte Membrane Protein Band 4.1 Like 1) Alias: 4.1N, NF2L1 ERBB4 (Erb-B2 Receptor Tyrosine Kinase 4) Alias: HER4 GRIN1 (Glutamate Ionotropic Receptor NMDA Type Subunit 1) Alias: NMD-R1, NR1, NMDAR1 GRIN2B (Glutamate Ionotropic Receptor NMDA Type Subunit 2B) Alias: NR2B, NMDAR2B HIVEP2 (Human Immunodeficiency Virus Type I Enhancer Binding Protein 2) Alias: MIBP1, PRDII-BF1 ITSN1 (Intersectin 1) Alias: SH3D1A, ITSN KCNQ2 (Potassium Voltage-Gated Channel Subfamily Q Member 2) Alias: KV7.2, BFNC, ENB1 KCNQ5 (Potassium Voltage-Gated Channel Subfamily Q Member 5) Alias: KV7.5 MYT1L (Myelin Transcription Factor 1 Like) No common aliases NBEA (Neurobeachin) Alias: A830005K05Rik KIF1A (Kinesin Family Member 1A) Alias: KIAA4012 | Autosomal dominant non-syndromic intellectual disability (ADNSID) is a type of intellectual disability inherited in an autosomal dominant pattern, meaning only one copy of the mutated gene from either parent is sufficient to cause the condition. Unlike syndromic intellectual disabilities, ADNSID is characterized by cognitive impairment without additional physical, neurological, or metabolic abnormalities. The severity of the intellectual disability can vary widely among affected individuals. Genetic mutations in various genes, such as SYNGAP1, ARID1B, and CHD2, have been associated with ADNSID. Diagnosis typically involves genetic testing, and management focuses on supportive therapies tailored to the individual's needs. | protein phosphatase 3 catalytic subunit alpha;RAB11A, member RAS oncogene family;calcium/calmodulin dependent protein kinase II alpha;calcium/calmodulin dependent protein kinase II beta;DEAF1 transcription factor;mediator complex subunit 12L;zinc finger MYND-type containing 11;cadherin 15;transient receptor potential cation channel subfamily M member 3;lysine demethylase 5B;ASH1 like histone lysine methyltransferase;casein kinase 2 beta;cut like homeobox 1;kirre like nephrin family adhesion molecule 3;clathrin heavy chain;methyl-CpG binding domain protein 5;prickle planar cell polarity protein 2;chromosome alignment maintaining phosphoprotein 1;dedicator of cytokinesis 8;delta like canonical Notch ligand 1;SET nuclear proto-oncogene;BR serine/threonine kinase 2;synaptic Ras GTPase activating protein 1;transcription factor 4;calcium voltage-gated channel subunit alpha1 I;calcium voltage-gated channel auxiliary subunit gamma 2;capicua transcriptional repressor;SET domain containing 1B, histone lysine methyltransferase;TAO kinase 1;dynein cytoplasmic 1 heavy chain 1;eukaryotic translation elongation factor 1 alpha 2;erythrocyte membrane protein band 4.1 like 1;erb-b2 receptor tyrosine kinase 4;glutamate ionotropic receptor NMDA type subunit 1;glutamate ionotropic receptor NMDA type subunit 2B;HIVEP zinc finger 2;intersectin 1;potassium voltage-gated channel subfamily Q member 2;potassium voltage-gated channel subfamily Q member 5;myelin transcription factor 1 like;neurobeachin;kinesin family member 1A | N2A (Neuro-2a) - Mouse neuroblastoma cells. NIH 3T3 - Mouse fibroblast cells. C2C12 - Mouse myoblast cells. PC-3 - Human prostate cancer cells. | ||
| 68 | Autosomal dominant omodysplasia | fewer than 50 cases reported in the medical literature worldwide | FZD2 | Frizzled-2 Fz-2 Hfz2 | Autosomal dominant omodysplasia is a rare genetic disorder characterized by distinctive skeletal abnormalities, particularly affecting the long bones in the arms and legs (humerus and femur). Individuals with this condition often have short stature, shortened and bowed limbs, and characteristic facial features such as a prominent forehead, midface hypoplasia, and a broad nasal bridge. The condition is inherited in an autosomal dominant manner, meaning a single copy of the altered gene in each cell is sufficient to cause the disorder. Mutations in the gene GPC6 are commonly associated with autosomal dominant omodysplasia. | frizzled class receptor 2 | HEK293-Human embryonic kidney cells HCT116 -Human colon cancer cells IMR-90-Human lung fibroblast cells Rat-1-Rat fibroblast cell lines RLE-6TN-Rat lung epithelial cells Rat smooth muscle cells | ||
| 69 | Autosomal dominant osteopetrosis type 1 | approximately 1 in 20,000 individuals | LRP5 | LR3 LRP-5 HBM (High Bone Mass) BMND1 (Bone Mass Density 1) EVR1 (Exudative Vitreoretinopathy 1) OPPG (Osteoporosis-Pseudoglioma Syndrome) | Autosomal dominant osteopetrosis type 1 (ADO1), also known as osteopetrosis tarda, is a rare genetic disorder characterized by increased bone density and abnormal bone growth. Unlike other forms of osteopetrosis, ADO1 is typically less severe and presents later in life, often during adolescence or adulthood. The disorder results from mutations in the LRP5 gene, which plays a crucial role in bone metabolism. Symptoms may include fractures, scoliosis, osteoarthritis, and bone pain. Diagnosis is usually confirmed through radiographic imaging and genetic testing. Treatment focuses on managing symptoms and preventing complications. | LDL receptor related protein 5 | MG-63-Human osteoblast cells HEK293-Human embryonic kidney cells HCT116 -Human colorectal cancer cells UMR-106 -Rat osteoblast cells Rat mesenchymal stem cells (MSCs) Rat-1 -Rat fibroblast cell lines | ||
| 70 | Autosomal dominant polycystic kidney disease | 1 in 400 to 1 in 1,000 individuals worldwide | ALG9;DNAJB11;BICC1;GANAB;IFT140;PKD2;PKD1 | ALG9 (Alpha-1,2-Mannosyltransferase ALG9) Alias: AAG9, ALG9A, CDG-IL, DPAGT4, DIBD1 DNAJB11 (DnaJ Heat Shock Protein Family (Hsp40) Member B11) Alias: ERdj3, HSJ-2, HSPF5 BICC1 (BicC Family RNA Binding Protein 1) Alias: BICC, FLJ20441, MGC19598 GANAB (Glucosidase II Alpha Subunit) Alias: GIIalpha, GCS2, GANB IFT140 (Intraflagellar Transport 140 Homolog) Alias: CILD16, FLJ20474, THM1 PKD2 (Polycystin 2, Transient Receptor Potential Cation Channel) Alias: APKD2, Polycystin-2, TRPP2 PKD1 (Polycystin 1, Transient Receptor Potential Cation Channel) Alias: APKD1, PBP, PC1 | Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the formation of numerous fluid-filled cysts in the kidneys. It is caused by mutations in either the PKD1 or PKD2 gene, leading to abnormal proliferation of renal tubular epithelial cells and cyst formation. ADPKD is inherited in an autosomal dominant pattern, meaning that a person only needs to inherit one copy of the mutated gene from either parent to develop the condition. Symptoms typically manifest in adulthood and may include abdominal pain, hypertension, hematuria, and renal impairment. ADPKD is one of the most common inherited kidney disorders and is a leading cause of end-stage renal disease (ESRD) worldwide. Management focuses on symptom relief, preservation of renal function, and addressing complications such as hypertension and cyst infections. | ALG9 alpha-1,2-mannosyltransferase;DnaJ heat shock protein family (Hsp40) member B11;BicC family RNA binding protein 1;glucosidase II alpha subunit;intraflagellar transport 140;polycystin 2, transient receptor potential cation channel;polycystin 1, transient receptor potential channel interacting | HEK293-Human embryonic kidney cells HepG2 -Human liver cancer cells HCT116-Human colorectal cancer cells Human renal proximal tubular cells ARPE-19-Human retinal pigment epithelial cells Human fibroblast cells (often derived from patients with ciliopathies) Rat hepatocyte cells ( primary rat liver cells) Rat-1-Rat fibroblast cells NRK-52E-Rat kidney cells | ||
| 71 | Autosomal dominant primary microcephaly | 1 in 10,000 to 1 in 250,000 births | LMNB1;DPP6 | LMNB1 (Lamin B1) Alias: LMN2, LMNB DPP6 (Dipeptidyl-Peptidase 6) Alias: DPPX, Dipeptidyl peptidase-like protein 6 | Autosomal dominant primary microcephaly (MCPH) is a rare genetic disorder characterized by significantly reduced head size at birth and impairment in brain development, leading to intellectual disability and developmental delays. It is inherited in an autosomal dominant pattern, meaning that one copy of the altered gene in each cell is sufficient to cause the disorder. Mutations in several genes, including ASPM, CDK5RAP2, and WDR62, among others, have been associated with MCPH. The severity of symptoms can vary, but affected individuals typically have mild to moderate intellectual disability and may experience other neurological abnormalities. Early diagnosis through genetic testing and supportive interventions are essential for managing the condition and optimizing outcomes. | lamin B1;dipeptidyl peptidase like 6 | HEK293-Human embryonic kidney cells NIH 3T3 -Human fibroblast cells HeLa-Human cancer cell lines Rat-1 -Rat fibroblast cell lines PC12 -Rat neuroblastoma cells | ||
| 72 | Autosomal dominant severe congenital neutropenia | 1 in 200,000 to 1 in 1 million individuals worldwide | SRP54;CLPB;TCIRG1;GFI1;ELANE | SRP54 (Signal Recognition Particle 54) Alias: SRP54, SRP54P, Ffh, SRP54M CLPB (Caseinolytic Mitochondrial Matrix Peptidase Chaperone Subunit B) Alias: CLPB, MGC:5166, ATP-dependent Clp protease ATP-binding subunit ClpB TCIRG1 (T Cell Immune Regulator 1, ATPase H+ Transporting V0 Subunit A3) Alias: TCIRG1, OSTM1, OC-116KDa, a3, a3V-ATPase, OSTM1 GFI1 (Growth Factor Independent 1 Transcriptional Repressor) Alias: GFI1, GFI-1, GFI1B ELANE (Elastase, Neutrophil Expressed) Alias: ELANE, HLE, NE, SCN1, ELA2 | Autosomal dominant severe congenital neutropenia (ADSCN) is a rare inherited disorder characterized by abnormally low levels of neutrophils, a type of white blood cell essential for fighting off bacterial infections. In ADSCN, affected individuals typically experience recurrent and severe bacterial infections starting from early childhood. The condition is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene from either parent is sufficient to cause the disorder. Mutations in genes such as ELANE (encoding elastase) and HAX1 (encoding HCLS1-associated protein X-1) are commonly associated with ADSCN. Treatment often involves the use of granulocyte colony-stimulating factor (G-CSF) to stimulate neutrophil production and reduce the frequency of infections. Bone marrow transplantation may be considered in severe cases. Early diagnosis and management are crucial for improving outcomes in individuals with ADSCN. | signal recognition particle 54;caseinolytic mitochondrial matrix peptidase chaperone subunit B;T cell immune regulator 1, ATPase H+ transporting V0 subunit a3;growth factor independent 1 transcriptional repressor;elastase, neutrophil expressed | HEK293-Human embryonic kidney cells HCT116-Human colon cancer cells HepG2-Human liver cells Rat-1 -Rat fibroblast cell lines PC12 - Rat neuroblastoma cells Rat liver cells (e.g., primary rat hepatocytes) | ||
| 73 | Autosomal erythropoietic protoporphyria | 1 to 9 cases per 1 million individuals worldwide | FECH | Ferrochelatase Protoporphyrin ferrochelatase Heme synthetase FEC | Autosomal erythropoietic protoporphyria (EPP) is a rare genetic disorder characterized by the impaired function of an enzyme called ferrochelatase, leading to the accumulation of protoporphyrin in the body, particularly in the bone marrow, blood, and skin. When exposed to sunlight, this excess protoporphyrin can cause painful photosensitivity reactions, including burning, itching, and swelling of the skin. EPP is inherited in an autosomal recessive manner, meaning that affected individuals inherit two mutated copies of the gene associated with the disorder, one from each parent. Management typically involves avoiding sunlight exposure and using protective clothing and sunscreen to minimize symptoms. | ferrochelatase | |||
| 74 | Autosomal recessive Alport syndrome | less than 1 in 100,000 individuals | COL4A4;COL4A3 | COL4A4 (Collagen Type IV Alpha 4 Chain) Alias: Goodpasture antigen-related protein, GBM2, Goodpasture syndrome antigen-related protein, GPAB COL4A3 (Collagen Type IV Alpha 3 Chain) Alias: BM143, Collagen alpha-3(IV) chain, BM600, Collagen IV alpha-3 chain, Goodpasture antigen-related protein, GBM1 | Autosomal recessive Alport syndrome is a genetic disorder characterized by kidney disease, hearing loss, and eye abnormalities. It is caused by mutations in genes involved in the production of type IV collagen, a key component of the basement membranes in the kidneys, ears, and eyes. Unlike the more common X-linked Alport syndrome, which primarily affects males, autosomal recessive Alport syndrome affects both males and females equally. Symptoms typically appear in childhood or early adulthood and can vary in severity. Kidney failure is a common complication, often requiring dialysis or kidney transplantation. Treatment focuses on managing symptoms and slowing the progression of kidney disease. | collagen type IV alpha 4 chain;collagen type IV alpha 3 chain | |||
| 75 | Autosomal recessive centronuclear myopathy | 1 in 50,000 to 1 in 200,000 individuals | RYR1;SPEG;TTN;BIN1 | RYR1 (Ryanodine Receptor 1) Alias: Ryanodine receptor 1, Malignant hyperthermia 1 SPEG (Striated Muscle Preferentially Expressed Protein Kinase) Alias: Striated muscle enriched protein kinase, FLJ11812, KIAA1313 TTN (Titin) Alias: Connectin, CMD1G, CMH9, TMD BIN1 (Bridging Integrator 1) Alias: Amphiphysin II, Myc box-dependent-interacting protein 1, SH3P9, CNM7 | Autosomal recessive centronuclear myopathy (ARCNM) is a rare genetic muscle disorder characterized by muscle weakness and wasting, particularly affecting muscles involved in movement and posture. It is caused by mutations in genes associated with muscle cell structure and function, such as the DNM2, BIN1, RYR1, and TTN genes. Symptoms typically manifest in infancy or early childhood and may include difficulties with motor skills, muscle weakness, respiratory problems, and delayed motor development. Diagnosis is usually made through genetic testing and muscle biopsy. Treatment focuses on managing symptoms and may include physical therapy, respiratory support, and other supportive measures. | ryanodine receptor 1;striated muscle enriched protein kinase;titin;bridging integrator 1 | |||
| 76 | Autosomal recessive cerebellar ataxia-movement disorder syndrome | 1–2.5/100,000 | VPS13D;VPS41 | VPS13D (Vacuolar Protein Sorting 13 Homolog D) Alias: CHAC, COH1, C9orf15, Vacuolar Protein Sorting 13D VPS41 (Vacuolar Protein Sorting 41 Homolog) Alias: C13orf12, hVPS41, Vacuolar Protein Sorting 41 | Autosomal recessive cerebellar ataxia-movement disorder syndrome (ARCA-MD) is a genetic disorder characterized by progressive cerebellar ataxia, which affects coordination and balance, along with various movement abnormalities. It typically manifests in childhood or adolescence. The syndrome encompasses a group of disorders with overlapping features, including impaired motor coordination, tremors, dystonia, and sometimes cognitive impairment. Mutations in various genes involved in cerebellar function and movement control contribute to the heterogeneous nature of ARCA-MD. Management often involves supportive care and symptomatic treatment, though research into targeted therapies is ongoing. | vacuolar protein sorting 13 homolog D;VPS41 subunit of HOPS complex | |||
| 77 | Autosomal recessive generalized dystrophic epidermolysis bullosa, intermediate form | 1 in 200,000 to 1 in 500,000 births globally | COL7A1 | EBA1 (Epidermolysis Bullosa, Dystrophic, Autosomal Recessive, Type IA) EBS1 (Epidermolysis Bullosa, Simplex, Dowling-Meara Type) KDEB1 (Kohlschütter-Tönz Syndrome) DEB (Dystrophic Epidermolysis Bullosa) EBS (Epidermolysis Bullosa Simplex) EDA (Epidermolysis Bullosa, Autosomal Dominant, Localized) MEDR (Medial Orbital Fibromatosis with Epidermolysis Bullosa) NBC1 (Naevus Butterfly Type, with Epidermolysis Bullosa) | Autosomal recessive generalized dystrophic epidermolysis bullosa (RDEB) is a severe genetic skin disorder characterized by blistering and erosions of the skin and mucous membranes. The intermediate form of RDEB lies between the severe and mild forms in terms of disease severity. In this intermediate subtype, blistering tends to occur at or shortly after birth, but may improve with age. However, individuals with the intermediate form still experience significant skin fragility, scarring, and complications such as impaired wound healing, joint contractures, and potential involvement of internal organs. RDEB is caused by mutations in the COL7A1 gene, which encodes type VII collagen, a crucial component of anchoring fibrils that attach the epidermis to the underlying dermis. Treatment primarily focuses on wound care, pain management, nutritional support, and prevention of complications. | collagen type VII alpha 1 chain | COS-7 - Monkey kidney fibroblast cells. Kera - Human keratinocytes (used in studies of skin biology). HDF - Human dermal fibroblasts | ||
| 78 | Autosomal recessive generalized dystrophic epidermolysis bullosa, severe form | 1 in 300,000 to 1 in 600,000 live births worldwide | MMP1;COL7A1 | " EBA1 (Epidermolysis Bullosa, Dystrophic, Autosomal Recessive, Type IA) EBS1 (Epidermolysis Bullosa, Simplex, Dowling-Meara Type) KDEB1 (Kohlschütter-Tönz Syndrome) DEB (Dystrophic Epidermolysis Bullosa) EBS (Epidermolysis Bullosa Simplex) EDA (Epidermolysis Bullosa, Autosomal Dominant, Localized) MEDR (Medial Orbital Fibromatosis with Epidermolysis Bullosa) NBC1 (Naevus Butterfly Type, with Epidermolysis Bullosa)" | Autosomal recessive generalized dystrophic epidermolysis bullosa (RDEB) is a severe genetic skin disorder characterized by blistering and erosions of the skin and mucous membranes in response to minor trauma or friction. It results from mutations in the COL7A1 gene, which encodes type VII collagen, a crucial protein for anchoring the skin layers together. In severe cases, patients experience widespread blistering, scarring, and deformities, leading to significant morbidity and mortality. Treatment focuses on wound care, infection prevention, and symptomatic management, as there is currently no cure for RDEB. | matrix metallopeptidase 1;collagen type VII alpha 1 chain | |||
| 79 | Autosomal recessive hypohidrotic ectodermal dysplasia | 1 in 100,000 births | EDARADD;WNT10A;EDAR;CSTB | EDARADD (EDAR-Associated Death Domain) Alias: EDARADD, ED1R-associated death domain WNT10A (Wnt Family Member 10A) Alias: WNT10A, HID, WNT12 EDAR (Ectodysplasin A Receptor) Alias: EDAR, ECTOD1, DL, ECTD1, HED CSTB (Cystatin B) Alias: CSTB, CST6, EPM1, STFB | Autosomal recessive hypohidrotic ectodermal dysplasia (AR-HED) is a rare genetic disorder characterized by abnormalities in the development of ectodermal structures such as skin, hair, teeth, and sweat glands. It is caused by mutations in genes such as EDA, EDAR, or EDARADD, which play crucial roles in the ectodermal development pathway. Individuals with AR-HED typically present with sparse or absent hair, missing or malformed teeth, and reduced ability to sweat, which can lead to overheating. Other features may include dry skin, abnormal nails, and respiratory problems due to abnormal development of the airway. The severity of symptoms can vary widely among affected individuals. Management of AR-HED involves addressing the symptoms through various interventions such as dental prosthetics for missing teeth, artificial sweat production methods, and skincare to manage dry skin. Genetic counseling is important for affected individuals and their families to understand the inheritance pattern and recurrence risk. | EDAR associated death domain;Wnt family member 10A;ectodysplasin A receptor;cystatin B | COS-7 - Monkey kidney fibroblast cells. A549 - Human lung carcinoma cells. HeLa - Human cervical cancer cells. | ||
| 80 | Autosomal recessive omodysplasia | less than 40 cases of omodysplasia have been described in the literature so far | GPC6 | DCDG-1 (Developmentally regulated GPC6) GPC6D (Glypican-6D) GYPC6 (Glypican 6) DKFZp686D01152 (a name used in some databases and annotations) | Autosomal recessive omodysplasia is a rare genetic disorder characterized by skeletal abnormalities such as short stature, bowed legs, and a small chest. It is caused by mutations in the LTBP3 gene, which plays a role in the development and maintenance of bone and connective tissue. This condition is inherited in an autosomal recessive manner, meaning that individuals must inherit two copies of the mutated gene (one from each parent) to manifest the disorder. Symptoms may vary in severity among affected individuals, and management typically involves supportive care to address the specific symptoms and complications associated with the condition. | glypican 6 | HeLa - Human cervical cancer cells. PC-3 - Human prostate cancer cells. COS-7 - Monkey kidney fibroblast cells. | ||
| 81 | Autosomal recessive primary microcephaly | approximately 1 in 10,000 to 1 in 250,000 live births worldwide | KNL1;COPB2;CIT;KIF14;PHC1;CDK5RAP2;CDK6;CENPJ;TAF13;STIL;TRAPPC14;CEP63;MFSD2A;WDR62;METTL5;SASS6;ASPM;MCPH1;PYCR2;CEP152;ANKLE2;CEP135;NCAPD3 | KNL1 (Kinetochore Scaffold 1) Alias: CASC5, Blinkin COPB2 (COPI Coat Complex Subunit Beta 2) Alias: Beta-COP CIT (Citron Rho-Interacting Serine/Threonine Kinase) Alias: Citron kinase KIF14 (Kinesin Family Member 14) Alias: KNSL2, KIF14B PHC1 (Polyhomeotic Homolog 1) Alias: BMI1, RING1B CDK5RAP2 (CDK5 Regulatory Subunit Associated Protein 2) Alias: CEP215 CDK6 (Cyclin Dependent Kinase 6) Alias: None CENPJ (Centromere Protein J) Alias: CPAP TAF13 (TATA-Box Binding Protein Associated Factor 13) Alias: None STIL (STIL Centriolar Assembly Protein) Alias: SIL, SCL/TAL1 Interrupting Locus TRAPPC14 (Trafficking Protein Particle Complex Subunit 14) Alias: TRS130 CEP63 (Centrosomal Protein 63) Alias: None MFSD2A (Major Facilitator Superfamily Domain Containing 2A) Alias: None WDR62 (WD Repeat Domain 62) Alias: KIAA1570 METTL5 (Methyltransferase Like 5) Alias: None SASS6 (SAS-6 Centriolar Assembly Protein) Alias: None ASPM (Abnormal Spindle Microtubule Assembly) Alias: MCPH5, MCPH, MGC111025 MCPH1 (Microcephalin 1) Alias: BRIT1, BRCT-repeat inhibitor of hTERT expression, Microcephalin PYCR2 (Pyrroline-5-Carboxylate Reductase Family Member 2) Alias: None CEP152 (Centrosomal Protein 152) Alias: None ANKLE2 (Ankyrin Repeat And LEM Domain Containing 2) Alias: KIAA1154 CEP135 (Centrosomal Protein 135) Alias: None NCAPD3 (Non-SMC Condensin II Complex Subunit D3) Alias: hCAP-D3, KIAA0154 | Autosomal recessive primary microcephaly (MCPH) is a rare genetic disorder characterized by significantly reduced head size at birth and impaired brain development, leading to intellectual disability and developmental delays. It is inherited in an autosomal recessive pattern, meaning both copies of the responsible gene (usually ASPM, WDR62, or other related genes) must be mutated for the condition to manifest. Individuals with MCPH typically have normal body proportions and no other major physical abnormalities. The severity of symptoms can vary, but affected individuals often face challenges in cognitive function, motor skills, and speech development. Treatment primarily focuses on supportive care and early intervention programs to maximize developmental outcomes. | ||||
| 82 | Autosomal recessive spastic ataxia of Charlevoix-Saguenay | 1 in 1,500 to 1 in 2,000 individuals | SACS | SACS SACsin ARSA Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay SPAX6 | Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder characterized by a triad of symptoms: spasticity (stiffness and involuntary muscle spasms), ataxia (lack of muscle coordination), and peripheral neuropathy (damage to nerves outside the brain and spinal cord). It is caused by mutations in the SACS gene and typically manifests in early childhood. Symptoms worsen over time, leading to progressive disability. ARSACS is primarily found in individuals of French-Canadian descent, particularly those from the Charlevoix-Saguenay-Lac-Saint-Jean region of Quebec, though cases have been reported in other populations. There is currently no cure for ARSACS, and treatment focuses on managing symptoms and providing supportive care. | sacsin molecular chaperone | NIH 3T3 - Mouse fibroblast cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. COS-7 - Monkey kidney fibroblast cells. PC12 - Rat pheochromocytoma cells. | ||
| 83 | Autosomal recessive spastic ataxia-optic atrophy-dysarthria syndrome | 1 to 5 cases per 100,000 individuals | MTPAP | MT-Poly(A) Polymerase PAPD1 (Poly(A) Polymerase Delta 1) MitoPLD (Mitochondrial Poly(A) Polymerase) POLRMT2L (Polymerase (RNA) Mitochondrial (DNA-Directed) Catalytic Subunit 2 Like) | Autosomal recessive spastic ataxia-optic atrophy-dysarthria (SPAX3) syndrome is a rare neurodegenerative disorder characterized by a combination of symptoms including progressive spasticity (stiffness and contraction of muscles), ataxia (lack of muscle coordination), optic atrophy (damage to the optic nerve leading to vision loss), and dysarthria (difficulty speaking due to impaired muscle control). This syndrome typically manifests in childhood or adolescence and progressively worsens over time. SPAX3 is caused by mutations in the TTPA gene, which encodes a protein involved in vitamin E metabolism. Treatment mainly focuses on managing symptoms and providing supportive care, as there is currently no cure for this condition. | mitochondrial poly(A) polymerase | |||
| 84 | Autosomal recessive spastic paraplegia type 11 | 1 to 2 per 1,000,000 individuals worldwide | SPG11 | KIAA1840 (KIAA1840 Gene) SPG11 Gene (Spastic Paraplegia 11 Gene) | Autosomal recessive spastic paraplegia type 11 (SPG11) is a rare neurodegenerative disorder characterized by progressive weakness and spasticity in the lower limbs, leading to difficulty walking. It typically begins in childhood or adolescence and worsens over time. SPG11 is caused by mutations in the SPG11 gene, which plays a role in maintaining the structure and function of nerve cells. Symptoms may also include intellectual disability, cognitive decline, and other neurological features. Treatment focuses on managing symptoms and supportive care, as there is currently no cure for SPG11. | SPG11 vesicle trafficking associated, spatacsin | |||
| 85 | Autosomal recessive spastic paraplegia type 15 | fewer than 1 in 1 million individuals worldwide | ZFYVE26 | SPG15 | Autosomal recessive spastic paraplegia type 15 (SPG15) is a rare neurological disorder characterized by progressive stiffness and weakness (spasticity) in the lower limbs. It is caused by mutations in the ZFYVE26 gene, which plays a role in regulating the transport of proteins within cells. Symptoms typically begin in childhood or adolescence and gradually worsen over time. In addition to spasticity, individuals with SPG15 may experience difficulty walking, muscle weakness, and may develop complications such as contractures or urinary problems. Treatment focuses on managing symptoms and may include physical therapy, medications to alleviate spasticity, and supportive care. | zinc finger FYVE-type containing 26 | N2A (Neuro-2a) - Mouse neuroblastoma cells. PC12 - Rat pheochromocytoma cells. COS-7 - Monkey kidney fibroblast cells. NIH 3T3 - Mouse fibroblast cells. | ||
| 86 | Autosomal recessive spastic paraplegia type 23 | fewer than 1 in 1 million individuals globally | DSTYK | Autosomal recessive spastic paraplegia type 23 (SPG23) is a rare neurological disorder characterized by progressive weakness and stiffness (spasticity) in the muscles of the lower limbs. It is caused by mutations in the gene encoding the protein receptor expression-enhancing protein 1 (REEP1). This condition typically presents in childhood or adolescence and gradually worsens over time, leading to difficulties with walking and mobility. Additional symptoms may include muscle wasting, urinary urgency, and sensory abnormalities. Management typically involves supportive therapies to alleviate symptoms and improve quality of life, as there is currently no cure for SPG23. | dual serine/threonine and tyrosine protein kinase | PC-3 - Human prostate cancer cells. A549 - Human lung carcinoma cells. PC-3 - Human prostate cancer cells. NIH 3T3 - Mouse fibroblast cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. | |||
| 87 | Autosomal recessive spondylocostal dysostosis | 1 in 1,000,000 births | HES7;LFNG;RIPPLY2;DLL3;MESP2 | HES7: Alias: Hairy and Enhancer of Split 7 LFNG: Alias: Lunatic Fringe RIPPLY2: Alias: Ripply Transcriptional Repressor 2 DLL3: Alias: Delta-Like Canonical Notch Ligand 3 Alternative Name: Hensen's Node Streak-Associated Protein (HNAP) MESP2: Alias: Mesoderm Posterior BHLH Transcription Factor 2 | Autosomal recessive spondylocostal dysostosis (ARSD) is a rare genetic disorder characterized by abnormalities in the spine and ribs. It typically presents with vertebral segmentation defects, such as fusion or abnormal separation of vertebrae, leading to a short trunk and a barrel-shaped chest. This condition is inherited in an autosomal recessive manner, meaning both copies of the gene must be mutated for the disorder to manifest. ARSD can cause respiratory complications due to the restricted chest cavity and may be associated with other skeletal abnormalities. Early diagnosis and management by a multidisciplinary team are essential for optimizing outcomes in affected individuals. | hes family bHLH transcription factor 7;LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase;ripply transcriptional repressor 2;delta like canonical Notch ligand 3;mesoderm posterior bHLH transcription factor 2 | N2A (Neuro-2a) - Mouse neuroblastoma cells. NIH 3T3 - Mouse fibroblast cells. COS-7 - Monkey kidney fibroblast cells. | ||
| 88 | B-cell chronic lymphocytic leukemia | Its prevalence increases with age, with the median age at diagnosis being around 70 years old | IGHV3-21;ATM;P2RX7;CCND1;RPS15;ARL11;POT1;IKZF3;TP53;IGHG1 | IGHV3-21: IGHV3-21, Immunoglobulin heavy variable 3-21 ATM: ATM, Ataxia Telangiectasia Mutated P2RX7: P2RX7, Purinergic Receptor P2X, Ligand-Gated Ion Channel 7 CCND1: CCND1, Cyclin D1 BCL1, B-Cell CLL/Lymphoma 1 RPS15: RPS15, Ribosomal Protein S15 ARL11: ARL11, ADP-Ribosylation Factor Like GTPase 11 POT1: POT1, Protection of Telomeres 1 IKZF3: IKZF3, Ikaros Family Zinc Finger 3 AIOLOS, IKAROS family zinc finger 3 TP53: TP53, Tumor Protein P53 p53, Cellular tumor antigen p53 IGHG1: IGHG1, Immunoglobulin heavy constant gamma 1 IgG1, Immunoglobulin G1 | B-cell chronic lymphocytic leukemia (CLL) is a type of cancer that affects white blood cells called lymphocytes, specifically B cells. In CLL, abnormal lymphocytes accumulate in the blood, bone marrow, and lymphoid tissues, crowding out normal blood cells and impairing immune function. It is typically a slow-growing leukemia and may not cause symptoms in the early stages. Common symptoms include enlarged lymph nodes, fatigue, weight loss, and frequent infections. CLL is diagnosed through blood tests and bone marrow biopsy. Treatment options vary depending on the stage and progression of the disease, ranging from watchful waiting to chemotherapy, immunotherapy, and targeted therapies. | immunoglobulin heavy variable 3-21;ATM serine/threonine kinase;purinergic receptor P2X 7;cyclin D1;ribosomal protein S15;ADP ribosylation factor like GTPase 11;protection of telomeres 1;IKAROS family zinc finger 3;tumor protein p53;immunoglobulin heavy constant gamma 1 (G1m marker) | NIH 3T3 - Mouse fibroblast cells. HeLa - Human cervical cancer cells. A549 - Human lung carcinoma cells. | ||
| 89 | Bainbridge-Ropers syndrome | fewer than 100 cases reported in the medical literature | ASXL3 | KIAA1797 ASX-Like Protein 3 ASXL3. | Bainbridge-Ropers syndrome (BRPS) is a rare genetic disorder resulting from mutations in the ASXL3 gene. It manifests with a spectrum of developmental and physical abnormalities, including significant intellectual disability, delayed speech and motor milestones, and feeding challenges. Individuals with BRPS often exhibit distinct facial features such as a prominent forehead, arched eyebrows, and a downturned mouth, along with hypotonia (low muscle tone). Behavioral issues, including traits associated with autism spectrum disorder, are also common. Diagnosis is primarily achieved through genetic testing, and treatment is focused on managing the specific symptoms and providing supportive therapies to enhance the quality of life. | ASXL transcriptional regulator 3 | N2A (Neuro-2a) - Mouse neuroblastoma cells. NIH 3T3 - Mouse fibroblast cells. COS-7 - Monkey kidney fibroblast cells. HeLa - Human cervical cancer cells. A549 - Human lung carcinoma cells. | ||
| 90 | Baller-Gerold syndrome | fewer than 50 cases reported in the medical literature worldwide | RECQL4 | RECQ4 RecQ protein-like 4 RECQ4 helicase RTS (Rothmund-Thomson syndrome gene) Rothmund-Thomson syndrome helicase SGS (subset of RAPADILINO syndrome gene) WRN3 (Werner syndrome, RecQ helicase-like 3) QDE3 (quelling deficient-3) DNA helicase Q4 | Baller-Gerold syndrome is a rare genetic disorder characterized by the combination of craniosynostosis (premature fusion of skull bones) and radial aplasia (absence or malformation of the radius bone in the forearm). Additional features can include growth retardation, distinctive facial features, and skeletal abnormalities. The condition is inherited in an autosomal recessive manner and is often associated with mutations in the RECQL4 gene, which plays a role in DNA repair and maintenance of genomic stability. | RecQ like helicase 4 | |||
| 91 | Band heterotopia | 1 in 100,000 to 1 in 1,000,000 individuals | EML1 | EMAP-115 EMAP115 ELP115 Echinoderm Microtubule Associated Protein Like 1 | Band heterotopia, also known as double cortex syndrome, is a rare neuronal migration disorder characterized by the presence of a band of grey matter located in the white matter, parallel to the cerebral cortex. This condition occurs due to a defect in the migration of neurons during brain development. It is often associated with epilepsy, intellectual disability, and developmental delays. Band heterotopia is usually linked to mutations in the DCX (doublecortin) gene, which is located on the X chromosome. It predominantly affects females, as the condition is often lethal in males who inherit the mutation. Diagnosis is typically made through imaging techniques like MRI, which reveals the characteristic double layer of cortex. | EMAP like 1 | |||
| 92 | Baraitser-Winter cerebrofrontofacial syndrome | < 1 / 1 000 000 | ACTB;ACTG1 | ACTB (Actin Beta): β-actin cytoplasmic actin gamma-actin F-actin, beta polypeptide ACTB actin, beta ACTG1 (Actin Gamma 1): γ-actin cytoplasmic actin 2 ACTG1 actin, gamma 1 cytoskeletal gamma-actin | Baraitser-Winter cerebrofrontofacial syndrome is a rare genetic disorder characterized by a distinct facial appearance, intellectual disability, and abnormalities of the brain and skull. Individuals with this syndrome typically have a prominent forehead, widely spaced eyes, small jaw, and a broad nasal bridge. They may also exhibit developmental delay, seizures, and structural brain anomalies such as abnormal folds or grooves. Baraitser-Winter syndrome is caused by mutations in genes associated with brain development, and its inheritance pattern is typically autosomal dominant. Due to its rarity, comprehensive understanding of the syndrome is still evolving. | actin beta;actin gamma 1 | |||
| 93 | Barber-Say syndrome | fewer than 1 in 1,000,000 individuals globally | TWIST2 | Dermo1-like protein Derml2 bHLHa39 TWIST-2 TWIST-related protein 2 Class A basic helix-loop-helix protein 39 | Barber-Say syndrome, also known as BSS, is an extremely rare genetic disorder characterized by distinctive facial features, such as sparse hair on the scalp, bushy eyebrows, prominent ears, and a broad nasal tip. Individuals with BSS may also exhibit intellectual disability, developmental delays, and skeletal abnormalities. This condition is caused by mutations in the TWIST2 gene, which plays a role in embryonic development. Management typically involves supportive care to address the specific needs of affected individuals | twist family bHLH transcription factor 2 | |||
| 94 | Bardet-biedl syndrome 10 | around 1 in 100,000 to 1 in 160,000 individuals worldwide | BBS10 | Bardet-Biedl syndrome 10 BARD1 BBS10A FLJ20203 C12orf58 | Bardet-Biedl syndrome (BBS) is a rare genetic disorder characterized by a wide range of symptoms that can affect various parts of the body. BBS is typically inherited in an autosomal recessive pattern, meaning both parents must pass on a defective gene for a child to develop the condition. BBS affects multiple systems of the body, leading to symptoms such as obesity, retinal degeneration causing vision loss, kidney abnormalities, intellectual disability, genital anomalies, and polydactyly (extra fingers or toes). Bardet-Biedl syndrome 10 (BBS10) is one of the known genetic subtypes of BBS, caused by mutations in the BBS10 gene. Mutations in this gene disrupt the function of cilia, which are microscopic hair-like structures found on the surface of cells and play crucial roles in various cellular processes. Individuals with BBS10 typically exhibit features consistent with BBS, such as obesity, vision problems, kidney abnormalities, and other associated symptoms. Management of BBS involves a multidisciplinary approach to address the various medical, developmental, and psychosocial aspects of the condition. | Bardet-Biedl syndrome 10 | N2A (Neuro-2a) - Mouse neuroblastoma cells. MCF-7 - Human breast cancer cells. NIH 3T3 - Mouse fibroblast cells. COS-7 - Monkey kidney fibroblast cells. | ||
| 95 | Bardet-biedl syndrome 12 | around 1 in 100,000 to 1 in 160,000 individuals worldwide | BBS12 | Bardet-Biedl syndrome 10 BARD1 BBS10A FLJ20203 C12orf58 | "Bardet-Biedl syndrome (BBS) is a rare genetic disorder characterized by a wide range of symptoms that can affect various parts of the body. BBS is typically inherited in an autosomal recessive pattern, meaning both parents must pass on a defective gene for a child to develop the condition. BBS affects multiple systems of the body, leading to symptoms such as obesity, retinal degeneration causing vision loss, kidney abnormalities, intellectual disability, genital anomalies, and polydactyly (extra fingers or toes). Bardet-Biedl syndrome 10 (BBS10) is one of the known genetic subtypes of BBS, caused by mutations in the BBS10 gene. Mutations in this gene disrupt the function of cilia, which are microscopic hair-like structures found on the surface of cells and play crucial roles in various cellular processes. Individuals with BBS10 typically exhibit features consistent with BBS, such as obesity, vision problems, kidney abnormalities, and other associated symptoms. Management of BBS involves a multidisciplinary approach to address the various medical, developmental, and psychosocial aspects of the condition." | Bardet-Biedl syndrome 12 | N2A (Neuro-2a) - Mouse neuroblastoma cells. MCF-7 - Human breast cancer cells. NIH 3T3 - Mouse fibroblast cells. COS-7 - Monkey kidney fibroblast cells. | ||
| 96 | Becker nevus syndrome | affects approximately 0.5-1% of the population | ACTB | ACTB (official symbol) β-actin Beta-actin ACTB1 PS1TP5BP1 BRWS1 Actin, beta cytoskeletal beta-actin actin, cytoplasmic 1 beta-actin-like protein 2 | Becker's nevus syndrome is a rare condition characterized by the presence of Becker's nevus, a large, irregularly shaped, pigmented birthmark often accompanied by coarse hair growth. Alongside the nevus, individuals may exhibit various features such as muscle, breast, or skeletal abnormalities on the same side of the body as the nevus. These abnormalities can vary widely in severity and presentation. Becker's nevus syndrome primarily affects males, though it can occur in females as well. The exact cause of the syndrome is unknown, but it's believed to involve a combination of genetic and hormonal factors. Treatment options typically focus on managing the cosmetic appearance of the nevus and addressing any associated complications. | actin beta | PC12 - Rat pheochromocytoma cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. NIH 3T3 - Mouse fibroblast cells. | ||
| 97 | Benign recurrent intrahepatic cholestasis type 1 | 1 in 100,000 to 200,000 individuals | ATP8B1 | FIC1 ATPICD ATPICDNL ATPase, Class I, Type 8B, Member 1 P4-ATPase flippase complex alpha subunit ATP8B1 FIC1P MDR3 | Benign recurrent intrahepatic cholestasis type 1 (BRIC1) is a rare genetic disorder characterized by recurrent episodes of liver dysfunction. It typically begins in childhood or early adulthood. BRIC1 is caused by mutations in the ATP8B1 gene, which is involved in bile secretion. These mutations impair the normal flow of bile from the liver, leading to symptoms such as severe itching, jaundice, and fatigue during episodes. In between episodes, liver function may return to normal. Treatment primarily focuses on managing symptoms, such as with medications to relieve itching, but liver transplantation may be necessary in severe cases. | ATPase phospholipid transporting 8B1 | |||
| 98 | Beta-mannosidosis | fewer than 1 in 1 million individuals globally | MANBA | Beta-mannosidase Lysosomal beta-mannosidase Beta-D-mannosidase EC 3.2.1.25 (Enzyme Commission number) | Beta-mannosidosis is a rare inherited metabolic disorder characterized by a deficiency in the enzyme beta-mannosidase, which is responsible for breaking down complex sugar molecules in the body. This deficiency leads to the accumulation of mannose-containing oligosaccharides in various tissues and organs, resulting in a range of symptoms including developmental delay, intellectual disability, hearing loss, skeletal abnormalities, facial dysmorphism, and recurrent infections. The severity of symptoms can vary widely among affected individuals. Beta-mannosidosis follows an autosomal recessive pattern of inheritance, meaning that individuals must inherit two copies of the defective gene (one from each parent) to develop the disorder. Treatment options are currently limited and mainly focus on managing symptoms and providing supportive care. | mannosidase beta | N2A (Neuro-2a) - Mouse neuroblastoma cells. SH-SY5Y - Human neuroblastoma cells. A549 - Human lung carcinoma cells. COS-7 - Monkey kidney fibroblast cells. | ||
| 99 | Bilateral multicystic dysplastic kidney | around 1 in 4,300 live births | HNF1B | TCF2 (Transcription Factor 2) LFB1 (Liver-specific Factor 1) MODY5 (Maturity-Onset Diabetes of the Young 5) LF-B1 (Liver Factor B1) TCF-2 (Transcription Factor 2) VHNF1 (Variant Hepatocyte Nuclear Factor 1) | Bilateral multicystic dysplastic kidney (BMDK) is a congenital condition where both kidneys develop multiple cysts of varying sizes instead of normal kidney tissue. This results in non-functional kidneys that are unable to filter waste from the blood or produce urine. BMDK is typically diagnosed prenatally or in infancy through imaging studies. It is considered a rare condition and may be associated with other anomalies or genetic syndromes. Treatment involves managing associated complications and often includes renal replacement therapy such as dialysis or kidney transplantation. | HNF1 homeobox B | HEK293-Human embryonic kidney cells HepG2-Human liver cells RPTEC/TERT1-Human renal proximal tubular epithelial cells NRK-52E-Rat kidney epithelial cells | ||
| 100 | Bloom syndrome | 1 in 48,000 to 1 in 1,000,000 individuals worldwide | BLM | RECQL2 (RecQ Like Helicase 2) BS (Bloom Syndrome protein) RECQ3 (RecQ DNA helicase 3) RECQ2 (RecQ DNA helicase 2) BLMC (Bloom Syndrome protein) RECQL3 (RecQ Like Helicase 3) | Bloom syndrome is a rare autosomal recessive disorder characterized by short stature, sun-sensitive skin changes, and a predisposition to various cancers. It results from mutations in the BLM gene, which is involved in DNA repair. Individuals with Bloom syndrome typically exhibit growth deficiency, a high-pitched voice, and a characteristic facial appearance. They are also prone to developing cancers at an early age, particularly leukemia and lymphoma, as well as solid tumors like colon, breast, and ovarian cancer. Bloom syndrome is inherited in an autosomal recessive manner, meaning both parents must carry a copy of the mutated gene for a child to inherit the disorder. | BLM RecQ like helicase | HEK293-Human embryonic kidney cells BJ-Human fibroblasts HeLa-Human cancer cell lines Rat-1-Rat fibroblasts PC12-Rat neuroblastoma cells | ||
| 101 | Blue rubber bleb nevus | less than 1 in 200,000 individuals | TEK | TIE2 VMCM CD202B | Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder characterized by the presence of multiple vascular lesions, known as rubbery blue nodules or blebs, on the skin and internal organs. These lesions are composed of abnormal blood vessels and can cause various symptoms depending on their location, such as gastrointestinal bleeding, anemia, and pain. BRBNS is typically present from birth or develops early in childhood. It is caused by mutations in the TEK gene, which plays a role in blood vessel formation. Treatment may involve managing symptoms and, in some cases, surgical removal of problematic lesions. | TEK receptor tyrosine kinase | ARPE-19-Human retinal pigment epithelial cells HEK293-Human embryonic kidney cells NIH 3T3-Human fibroblasts Rat retinal cells (e.g., primary rat retinal cells or cell lines) Rat-1-Rat fibroblast cells | ||
| 102 | Boomerang dysplasia | less than 1 in 1 million births | FLNB | FLN2 FLN-B ABP-278 TABP FH1 FLN2L MPD4 N-RAP | Boomerang dysplasia is an extremely rare skeletal disorder characterized by severe bone abnormalities, typically evident on prenatal ultrasound or shortly after birth. It is named for the characteristic boomerang-shaped bowed femurs seen in affected individuals. Other features may include short limbs, abnormal ossification of bones, and underdeveloped or absent bones in the hands and feet. Boomerang dysplasia is usually lethal either before or shortly after birth due to respiratory insufficiency caused by thoracic abnormalities. The genetic cause of this condition is not fully understood, but it is believed to be inherited in an autosomal dominant manner with variable expressivity. Due to its rarity, management typically focuses on supportive care. | filamin B | HeLa cells: human cervical cancer cells U2OS: human osteosarcoma cell line Endothelial cells: Expression is observed in cells involved in blood vessel formation. Rat primary osteoblasts: osteoblast cells. Rat vascular smooth muscle cells (VSMCs) Rat fibroblasts | ||
| 103 | Bowen-Conradi syndrome | fewer than 1 in 1,000,000 individuals worldwide | EMG1 | MGC52498 EMG1 N-terminal domain-containing protein Essential for mitotic growth protein 1 60S ribosomal subunit assembly protein 1 Nucleolar protein EMG1 homolog | Bowen-Conradi syndrome is a rare genetic disorder characterized by severe growth and developmental delays, distinctive facial features, and various physical abnormalities. It is an autosomal recessive condition most commonly found in individuals of Hutterite ancestry. The syndrome is caused by mutations in the EMG1 gene, which plays a crucial role in ribosome biogenesis. Affected individuals often have a small head, prominent nose, micrognathia (small jaw), and significant feeding difficulties. Most children with Bowen-Conradi syndrome do not survive beyond infancy due to complications such as severe failure to thrive and respiratory issues. | EMG1 N1-specific pseudouridine methyltransferase | HeLa cells: Cervical cancer cell lines HEK293 cells: Human embryonic kidney cellsMCF-7 cells: A breast cancer cell line Rat hepatocytes: Primary liver cells Rat neural progenitor cells Rat fibroblasts: role in ribosome production | ||
| 104 | Brachydactyly-arterial hypertension syndrome | fewer than 100 cases reported in the medical literature worldwid | PDE3A1 | CGI-PDE A Cyclic GMP-inhibited phosphodiesterase A cGIPDE cGI-PDE CGI-PDE | Brachydactyly-arterial hypertension syndrome is a rare genetic disorder characterized by the combination of shortened digits (brachydactyly) and high blood pressure (arterial hypertension). This syndrome is caused by mutations in the PDE3A gene, which encodes an enzyme involved in the regulation of vascular tone and bone development. Individuals with this condition typically exhibit short fingers and toes and may develop hypertension at a young age, which can increase the risk of cardiovascular complications. The syndrome is inherited in an autosomal dominant pattern. Management usually involves monitoring and treating hypertension to reduce associated health risks. | phosphodiesterase 3A | PC-3 - Human prostate cancer cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. PC-3 - Human prostate cancer cells. A549 - Human lung carcinoma cells. COS-7 - Monkey kidney fibroblast cells. | ||
| 105 | Branchioskeletogenital syndrome | fewer than 20 reported cases in the medical literature | CDH11 | OSF-4 (Osteoblast-specific factor 4) OB-cadherin (Osteoblast-cadherin) Cadherin-11 | Branchioskeletogenital syndrome, also known as Wildervanck-Smith syndrome, is an extremely rare genetic disorder characterized by a combination of branchial, skeletal, and genital anomalies. Individuals with this syndrome may exhibit branchial cysts, fistulas, or sinuses; skeletal malformations such as cervical vertebrae fusion (Klippel-Feil anomaly); and genital anomalies including ambiguous genitalia. Diagnosis is primarily based on clinical features, and genetic testing may be used for confirmation. Management typically involves a multidisciplinary approach to address the diverse physical anomalies present from birth. | phosphodiesterase 3A | PC-3 - Human prostate cancer cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. PC-3 - Human prostate cancer cells. A549 - Human lung carcinoma cells. COS-7 - Monkey kidney fibroblast cells. |