long QT syndrome

disease
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Also known as ventricular arrhythmia associated with long QT syndrome

Summary

long QT syndrome (MONDO:0002442) is a disease with 75 cohort genes and 66 clinical trials. The dominant Reactome pathway is Muscle contraction (23 cohort genes). Top therapeutic interventions include ibutilide, progesterone, and dofetilide.

At a glance

  • Cohort genes: 75
  • ClinVar variants: 13,505
  • Clinical trials: 66

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namelong QT syndrome
Mondo IDMONDO:0002442
MeSHD008133
DOIDDOID:2843
ICD-10-CMI45.81
NCITC34786
UMLSC0023976
MedGen44193
GARD0027044
Is cancer (heuristic)no

Also known as: long QT syndrome · ventricular arrhythmia associated with long QT syndrome

Data availability: 13,505 ClinVar variants · 1 GenCC gene-disease record · 4 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › syndromic diseaselong QT syndrome

Related subtypes (1183): Neu-Laxova syndrome, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, syndromic intellectual disability, abdominal obesity-metabolic syndrome, fibrogenesis imperfecta ossium, Fanconi renotubular syndrome, palindromic rheumatism, hepatorenal syndrome, Potter sequence, vertebral artery insufficiency, sick sinus syndrome, Tietze syndrome, toxic shock syndrome, capillary leak syndrome, dumping syndrome, FG syndrome, basilar artery insufficiency, Treacher-Collins syndrome, superior mesenteric artery syndrome, disappearing bone disease, Brown-Sequard syndrome, Froelich syndrome, diffuse infiltrative lymphocytosis syndrome, Capgras syndrome, compartment syndrome, central sleep apnea syndrome, irritable bowel syndrome, nephrotic syndrome, myalgic encephalomeyelitis/chronic fatigue syndrome, acute coronary syndrome, fibromyalgia, substance withdrawal syndrome, acute chest syndrome, Barre-Lieou syndrome, cauda equina syndrome, Kluver-Bucy syndrome, Miller Fisher syndrome, persian gulf syndrome, Reye syndrome, thoracic outlet syndrome, Waterhouse-Friderichsen syndrome, Wissler syndrome, acute respiratory distress syndrome, Achenbach syndrome, miliaria, anterior spinal artery syndrome, burning mouth syndrome, dry eye syndrome, empty sella syndrome, euthyroid sick syndrome, lateral medullary syndrome, subclavian steal syndrome, tarsal tunnel syndrome, tethered spinal cord syndrome, branchio-oto-renal syndrome, prune belly syndrome, Achard syndrome, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, Finnish type amyloidosis, Angelman syndrome, aniridia-absent patella syndrome, ankyloblepharon filiforme adnatum-cleft palate syndrome, Townes-Brocks syndrome, obstructive sleep apnea syndrome, Lown-Ganong-Levine syndrome, Behcet disease, brachydactyly-arterial hypertension syndrome, brachydactyly type A2, fibular aplasia-ectrodactyly syndrome, brachydactyly-nystagmus-cerebellar ataxia syndrome, Sillence syndrome, Brachymorphism-onychodysplasia-dysphalangism syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, dilated cardiomyopathy 1A, cat-eye syndrome, cerebrocostomandibular syndrome, Alagille syndrome, autosomal dominant chondrodysplasia punctata, cleidocranial dysplasia 1, cleidorhizomelic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Cri-du-chat syndrome, autosomal dominant deafness - onychodystrophy syndrome, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, Duane retraction syndrome, 3-M syndrome, dyschondrosteosis-nephritis syndrome, hereditary benign intraepithelial dyskeratosis, encephalopathy, recurrent, of childhood, Camurati-Engelmann disease, Felty syndrome, chromosome 16p12.1 deletion syndrome, 520kb, Frasier syndrome, Gamstorp-Wohlfart syndrome, Tourette syndrome, glaucoma-sleep apnea syndrome, renal cysts and diabetes syndrome, hypotrichosis-lymphedema-telangiectasia syndrome (grouping), GMS syndrome, gray platelet syndrome, hand-foot-genital syndrome, facial hemiatrophy, Bencze syndrome, alpha thalassemia-intellectual disability syndrome type 1, Gilbert syndrome, mullerian duct anomalies-limb anomalies syndrome, hypoparathyroidism-deafness-renal disease syndrome, chromosome 18p deletion syndrome, Pallister-Hall syndrome, ichthyosis-cheek-eyebrow syndrome, Jacobsen syndrome, palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome, palmoplantar keratoderma-esophageal carcinoma syndrome, Kleine-Levin syndrome, angioosteohypertrophic syndrome, congenital laryngeal web, Lenz-Majewski hyperostotic dwarfism, Noonan syndrome with multiple lentigines, lymphedema-cerebral arteriovenous anomaly syndrome, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, yellow nail syndrome, lymphedema-distichiasis syndrome, Nager acrofacial dysostosis, jaw-winking syndrome, Marfan syndrome, Melkersson-Rosenthal syndrome, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome, microgastria-limb reduction defect syndrome, Mobius syndrome, muscular atrophy-ataxia-retinitis pigmentosa-diabetes mellitus syndrome, nail-patella syndrome, Schilbach-Rott syndrome, syndromic orbital border hypoplasia, Buschke-Ollendorff syndrome, nasopalpebral lipoma-coloboma syndrome, Perry syndrome, Poland syndrome, polydactyly-myopia syndrome, Greig cephalopolysyndactyly syndrome, Prader-Willi syndrome, Guttmacher syndrome, Currarino triad, Hutchinson-Gilford progeria syndrome, progeria-short stature-pigmented nevi syndrome, Liddle syndrome, exfoliation syndrome, ptosis-strabismus-ectopic pupils syndrome, radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome, radial ray hypoplasia-choanal atresia syndrome, Roussy-Levy syndrome, Silver-Russell syndrome, Ruvalcaba syndrome, oculodental syndrome, Rutherfurd type, aplasia of lacrimal and salivary glands, scalp defects-postaxial polydactyly syndrome, ulnar-mammary syndrome, septooptic dysplasia, Czeizel-Losonci syndrome, polycystic ovary syndrome, stiff-person syndrome, syndactyly-polydactyly-ear lobe syndrome, HELLP syndrome, double uterus-hemivagina-renal agenesis syndrome, VACTERL/vater association, posterior fusion of lumbosacral vertebrae-blepharoptosis syndrome, ptosis-vocal cord paralysis syndrome, Freeman-Sheldon syndrome, Williams syndrome, Denys-Drash syndrome, Wolf-Hirschhorn syndrome, ablepharon macrostomia syndrome, acrocallosal syndrome, PAGOD syndrome, alopecia - intellectual disability syndrome, mitochondrial DNA depletion syndrome 4a, Alstrom syndrome, aniridia-cerebellar ataxia-intellectual disability syndrome, aniridia-renal agenesis-psychomotor retardation syndrome, aplasia cutis congenita-intestinal lymphangiectasia syndrome, fetal akinesia deformation sequence, blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome, Bloom syndrome, Elsahy-Waters syndrome, campomelia, Cumming type, camptomelic syndrome, long-limb type, congenital cataract-ichthyosis syndrome, colobomatous optic disc-macular atrophy-chorioretinopathy syndrome, hepatic fibrosis-renal cysts-intellectual disability syndrome, Charcot-Marie-Tooth disease-hearing loss-intellectual disability syndrome, CHARGE syndrome, Aagenaes syndrome, infantile choroidocerebral calcification syndrome, Yunis-Varon syndrome, corneal dystrophy-perceptive deafness syndrome, cortical blindness-intellectual disability-polydactyly syndrome, Crigler-Najjar syndrome, cataract-nephropathy-encephalopathy syndrome, Fraser syndrome, cystic fibrosis-gastritis-megaloblastic anemia syndrome, cystinuria, DOORS syndrome, high myopia-sensorineural deafness syndrome, dermochondrocorneal dystrophy, nephrogenic diabetes insipidus-intracranial calcification syndrome, diverticulosis of bowel, hernia, and retinal detachment, Dyggve-Melchior-Clausen disease, cerebellar ataxia, intellectual disability, and dysequilibrium, ectrodactyly-polydactyly syndrome, Bonnemann-Meinecke-Reich syndrome, epidermolysis bullosa simplex 5B, with muscular dystrophy, Wolcott-Rallison syndrome, ermine phenotype, eyebrow duplication-syndactyly syndrome, Fanconi-like syndrome, gingival fibromatosis-facial dysmorphism syndrome, frontofacionasal dysplasia, Fryns syndrome, German syndrome, Bernard-Soulier syndrome, triple-A syndrome, Grubben-de Cock-Borghgraef syndrome, mullerian derivatives-lymphangiectasia-polydactyly syndrome, Hirschsprung disease-hearing loss-polydactyly syndrome, Hirschsprung disease-nail hypoplasia-dysmorphism syndrome, Holzgreve-Wagner-Rehder syndrome, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, growth delay-hydrocephaly-lung hypoplasia syndrome, Dubin-Johnson syndrome, ornithine translocase deficiency, acrofrontofacionasal dysostosis 2, hypertrichotic osteochondrodysplasia Cantu type, hypergonadotropic hypogonadism-cataract syndrome, primary hypergonadotropic hypogonadism-partial alopecia syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, hypospadias-intellectual disability, Goldblatt type syndrome, Bamforth-Lazarus syndrome, ichthyosis-hepatosplenomegaly-cerebellar degeneration syndrome, ichthyosis-intellectual disability-dwarfism-renal impairment syndrome, Vici syndrome, channelopathy-associated congenital insensitivity to pain, autosomal recessive, Joubert syndrome with oculorenal defect, oculocerebrofacial syndrome, Kaufman type, Landau-Kleffner syndrome, laryngo-onycho-cutaneous syndrome, Laurence-Moon syndrome, Donohue syndrome, Miller-Dieker lissencephaly syndrome, Marinesco-Sjogren syndrome, Frank-Ter Haar syndrome, Mietens syndrome, mesomelic dwarfism-cleft palate-camptodactyly syndrome, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, metaphyseal dysostosis-intellectual disability-conductive deafness syndrome, microcephalic primordial dwarfism, Toriello type, Say-Barber-Miller syndrome, microcephaly and chorioretinopathy 1, Galloway-Mowat syndrome, microtia with meatal atresia and conductive deafness, mucopolysaccharidosis type 6, mulibrey nanism, lethal multiple pterygium syndrome, lethal congenital contracture syndrome 1, Schwartz-Jampel syndrome, Nathalie syndrome, nephronophthisis 1, nephropathy - deafness - hyperparathyroidism syndrome, nephrosis-deafness-urinary tract-digital malformations syndrome, Netherton syndrome, Norman-Roberts syndrome, cloacal exstrophy, ichthyosis-oral and digital anomalies syndrome, Primrose syndrome, familial osteodysplasia, Anderson type, multicentric osteolysis, nodulosis, and arthropathy, osteopenia-intellectual disability-sparse hair syndrome, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, Parana hard-skin syndrome, PEHO syndrome, Imerslund-Grasbeck syndrome, Peters plus syndrome, pili torti-developmental delay-neurological abnormalities syndrome, Rabson-Mendenhall syndrome, postaxial acrofacial dysostosis, Gitelman syndrome, Wiedemann-Rautenstrauch syndrome, Acrootoocular syndrome, holoprosencephaly-postaxial polydactyly syndrome, autosomal recessive multiple pterygium syndrome, Perlman syndrome, retinitis pigmentosa-intellectual disability-deafness-hypogenitalism syndrome, EEC syndrome, SHORT syndrome, Sjogren syndrome, spastic tetraplegia-retinitis pigmentosa-intellectual disability syndrome, corneal-cerebellar syndrome, spastic ataxia-corneal dystrophy syndrome, spondylocostal dysostosis-anal and genitourinary malformations syndrome, familial infantile bilateral striatal necrosis, subaortic stenosis-short stature syndrome, thrombocytopenia-absent radius syndrome, thyrocerebrorenal syndrome, Pendred syndrome, VACTERL with hydrocephalus, Weaver syndrome, Werner syndrome, Wernicke-Korsakoff syndrome, wooly hair-hypotrichosis-everted lower lip-outstanding ears syndrome, de Sanctis-Cacchione syndrome, corpus callosum agenesis-abnormal genitalia syndrome, Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome, X-linked lissencephaly with abnormal genitalia, X-linked myotubular myopathy-abnormal genitalia syndrome, Christianson syndrome, Armfield syndrome, Lesch-Nyhan syndrome, Atkin-Flaitz syndrome, alpha-thalassemia-myelodysplastic syndrome, deafness-intellectual disability, Martin-Probst type syndrome, fragile X-associated tremor/ataxia syndrome, fragile X syndrome, syndactyly-telecanthus-anogenital and renal malformations syndrome, X-linked dominant chondrodysplasia, Chassaing-Lacombe type, X-linked central congenital hypothyroidism with late-onset testicular enlargement, Meester-Loeys syndrome, Arts syndrome, X-linked mandibulofacial dysostosis, Abruzzo-Erickson syndrome, Aicardi syndrome, craniofrontonasal syndrome, deafness-hypogonadism syndrome, X-linked corneal dermoid, immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, hydrocephaly-cerebellar agenesis syndrome, keratosis follicularis-dwarfism-cerebral atrophy syndrome, laryngeal abductor paralysis-intellectual disability syndrome, oculocerebrorenal syndrome, Menkes disease, paraplegia-intellectual disability-hyperkeratosis syndrome, mucopolysaccharidosis type 2, orofaciodigital syndrome I, otopalatodigital syndrome type 1, Pallister-W syndrome, Rett syndrome, SCARF syndrome, Simpson-Golabi-Behmel syndrome, torticollis-keloids-cryptorchidism-renal dysplasia syndrome, trigonocephaly-short stature-developmental delay syndrome, ulnar hypoplasia-split foot syndrome, van den Bosch syndrome, Wildervanck syndrome, Kearns-Sayre syndrome, MELAS syndrome, MERRF syndrome, Pearson syndrome, proximal tubulopathy-diabetes mellitus-cerebellar ataxia syndrome, pancreatic hypoplasia-diabetes-congenital heart disease syndrome, chondrodysplasia-pseudohermaphroditism syndrome, Qazi Markouizos syndrome, familial developmental dysphasia, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, CODAS syndrome, lethal hemolytic anemia-genital anomalies syndrome, HEC syndrome, anophthalmia plus syndrome, infundibulopelvic stenosis-multicystic kidney syndrome, Ayme-Gripp syndrome, dilated cardiomyopathy 1E, diaphragmatic defect-limb deficiency-skull defect syndrome, skeletal dysplasia-epilepsy-short stature syndrome, Potocki-Shaffer syndrome, amelia cleft lip palate hydrocephalus iris coloboma, human HOXA1 syndromes, dyssegmental dysplasia-glaucoma syndrome, lung agenesis-heart defect-thumb anomalies syndrome, tetrasomy 12p, chromosome 18q deletion syndrome, lymphedema-atrial septal defects-facial changes syndrome, infantile convulsions and choreoathetosis, RHYNS syndrome, Pierre Robin sequence with pectus excavatum and rib and scapular anomalies, colobomatous macrophthalmia-microcornea syndrome, Marshall-Smith syndrome, distal monosomy 13q, MPI-congenital disorder of glycosylation, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, radioulnar synostosis-microcephaly-scoliosis syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type, complex regional pain syndrome type 1, temtamy preaxial brachydactyly syndrome, Diamond-Blackfan anemia 2, genitopatellar syndrome, Phelan-McDermid syndrome, hypotonia-cystinuria syndrome, DNA ligase IV deficiency, Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome, Duane-radial ray syndrome, psoriatic arthritis, neonatal ichthyosis-sclerosing cholangitis syndrome, skin fragility-woolly hair-palmoplantar keratoderma syndrome, tubulointerstitial nephritis and uveitis syndrome, caudal duplication, sweet syndrome, ichthyosis prematurity syndrome, Meacham syndrome, BNAR syndrome, PCWH syndrome, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome, B-cell immunodeficiency, distal limb anomalies, and urogenital malformations, MEDNIK syndrome, Cerebrorenodigital syndrome, fetal valproate syndrome, Goldberg-Shprintzen syndrome, Al-Gazali syndrome, CEDNIK syndrome, osteosclerosis-ichthyosis-premature ovarian failure syndrome, cortical dysplasia-focal epilepsy syndrome, DK1-congenital disorder of glycosylation, Potocki-Lupski syndrome, Pitt-Hopkins syndrome, XFE progeroid syndrome, deafness-infertility syndrome, COG1-congenital disorder of glycosylation, autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, microtia-eye coloboma-imperforation of the nasolacrimal duct syndrome, mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria, ANE syndrome, CLOVES syndrome, Hirschsprung disease-ganglioneuroblastoma syndrome, parkinsonism-dystonia, infantile, alpha 1-antitrypsin deficiency, COG5-congenital disorder of glycosylation, chromosome 13q14 deletion syndrome, deafness-lymphedema-leukemia syndrome, microcephaly-capillary malformation syndrome, EDICT syndrome, peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome, hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism, IMAGe syndrome, short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, microcephalic primordial dwarfism, Alazami type, intellectual disability-strabismus syndrome, estrogen resistance syndrome, Hartsfield-Bixler-Demyer syndrome, severe dermatitis-multiple allergies-metabolic wasting syndrome, alacrima, achalasia, and intellectual disability syndrome, familial episodic pain syndrome with predominantly lower limb involvement, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, tall stature-scoliosis-macrodactyly of the great toes syndrome, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome, retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome, polyendocrine-polyneuropathy syndrome, chronic atrial and intestinal dysrhythmia, motor developmental delay due to 14q32.2 paternally expressed gene defect, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, mandibulofacial dysostosis with alopecia, epilepsy with myoclonic atonic seizures, short stature, microcephaly, and endocrine dysfunction, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, PMP22-RAI1 contiguous gene duplication syndrome, acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome, familial progressive retinal dystrophy-iris coloboma-congenital cataract syndrome, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, Luscan-Lumish syndrome, even-plus syndrome, MIRAGE syndrome, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, intellectual disability-epilepsy-extrapyramidal syndrome, 48,XXYY syndrome, FRAXF syndrome, complex hereditary spastic paraplegia, aniridia-ptosis-intellectual disability-familial obesity syndrome, aniridia - intellectual disability syndrome, ankyloblepharon filiforme-imperforate anus syndrome, pentasomy X, Bardet-Biedl syndrome, anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome, Bartter syndrome, arachnodactyly-intellectual disability-dysmorphism syndrome, ataxia-photosensitivity-short stature syndrome, Brugada syndrome, Feingold syndrome, cardiomyopathy-cataract-hip spine disease syndrome, cataract - microcornea syndrome, autism-facial port-wine stain syndrome, cataract-intellectual disability-anal atresia-urinary defects syndrome, cataract-deafness-hypogonadism syndrome, syndromic craniosynostosis, drug rash with eosinophilia and systemic symptoms, multicentric reticulohistiocytosis, hereditary sensory and autonomic neuropathy with deafness and global delay, craniofacial microsomia, ring chromosome 10, Coffin-Siris syndrome, corpus callosum agenesis-double urinary collecting system syndrome, short rib-polydactyly syndrome, oromandibular-limb anomalies syndrome, hemophagocytic syndrome, cataract-glaucoma syndrome, diencephalic syndrome, hypereosinophilic syndrome, distal trisomy 14q, intellectual disability-cataracts-kyphosis syndrome, progressive familial intrahepatic cholestasis, thoraco-abdominal enteric duplication, oculomaxillofacial dysostosis, growth hormone insensitivity syndrome, syndromic dyslipidemia, macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, epiphyseal dysplasia-hearing loss-dysmorphism syndrome, eosinophilic granulomatosis with polyangiitis, axial mesodermal dysplasia spectrum, fetal hydantoin syndrome, vitamin K-antagonist embryofetopathy, fetal alcohol syndrome, methimazole embryofetopathy, Evans syndrome, Cornelia de Lange syndrome, cleft lip-retinopathy syndrome, cleft lip/palate-deafness-sacral lipoma syndrome, Crandall syndrome, syndromic microphthalmia, Cole-Carpenter syndrome, myotonic syndrome, Guillain-Barre syndrome, atypical hemolytic-uremic syndrome, Hennekam syndrome, Hernández-Aguirre Negrete syndrome, nodular neuronal heterotopia, Hirschsprung disease-type D brachydactyly syndrome, holoprosencephaly, hydrocephalus-obesity-hypogonadism syndrome, hydrocephalus-blue sclerae-nephropathy syndrome, xeroderma pigmentosum-Cockayne syndrome complex, Joubert syndrome with ocular defect, hypogonadism-mitral valve prolapse-intellectual disability syndrome, hypogonadotropic hypogonadism-retinitis pigmentosa syndrome, hypotrichosis-intellectual disability, Lopes type, congenital ichthyosis-microcephalus-tetraplegia syndrome, Hughes-Stovin syndrome, heart-hand syndrome, ptosis-upper ocular movement limitation-absence of lacrimal punctum syndrome, syndromic agammaglobulinemia, isotretinoin syndrome, microcornea-posterior megalolenticonus-persistent fetal vasculature-coloboma syndrome, Kabuki syndrome, Kenny-Caffey syndrome, muscular pseudohypertrophy-hypothyroidism syndrome, Kousseff syndrome, limb body wall complex, Lennox-Gastaut syndrome, Lowe-Kohn-Cohen syndrome, macrocephaly-short stature-paraplegia syndrome, primary ciliary dyskinesia, familial intestinal malrotation-facial anomalies syndrome, primary hypertrophic osteoarthropathy, Melhem-Fahl syndrome, lower limb deficiency-hypospadias syndrome, 8p23.1 microdeletion syndrome, sickle cell-beta-thalassemia disease syndrome, sickle cell-hemoglobin c disease syndrome, sickle cell-hemoglobin d disease syndrome, sickle cell-hemoglobin E disease syndrome, hereditary persistence of fetal hemoglobin-sickle cell disease syndrome, microcephaly-brain defect-spasticity-hypernatremia syndrome, microcephaly-microcornea syndrome, Seemanova type, Meier-Gorlin syndrome, Mikati-Najjar-Sahli syndrome, shoulder and girdle defects-familial intellectual disability syndrome, myopathy-growth delay-intellectual disability-hypospadias syndrome, Fuchs heterochromic iridocyclitis, microcephalic osteodysplastic primordial dwarfism types I and III, osteochondrodysplatic nanism-deafness-retinitis pigmentosa syndrome, arthrogryposis-renal dysfunction-cholestasis syndrome, oculo-skeletal-renal syndrome, olivopontocerebellar atrophy-deafness syndrome, Opitz G/BBB syndrome, imperforate oropharynx-costo vetebral anomalies syndrome, Bruck syndrome, osteoporosis-macrocephaly-blindness-joint hyperlaxity syndrome, calciphylaxis, recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome, X-linked ichthyosis syndrome, autoimmune polyendocrinopathy, renal caliceal diverticuli-deafness syndrome, tempi syndrome, syndromic oculocutaneous albinism, short stature-deafness-neutrophil dysfunction-dysmorphism syndrome, congenital varicella syndrome, polyneuropathy-intellectual disability-acromicria-premature menopause syndrome, celiac trunk compression syndrome, hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome, fetal cytomegalovirus syndrome, Reunion island Larsen syndrome, 46,XX disorder of sex development-anorectal anomalies syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Baraitser-Winter cerebrofrontofacial syndrome, mirror polydactyly-vertebral segmentation-limbs defects syndrome, intellectual disability-hypotonia-skin hyperpigmentation syndrome, congenital hereditary facial paralysis-variable hearing loss syndrome, intellectual disability-microcephaly-phalangeal-facial abnormalities syndrome, Mayer-Rokitansky-Kuster-Hauser syndrome, developmental and speech delay due to SOX5 deficiency, Spigelian hernia-cryptorchidism syndrome, autosomal recessive leukoencephalopathy-ischemic stroke-retinitis pigmentosa syndrome, severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, X-linked spasticity-intellectual disability-epilepsy syndrome, spina bifida-hypospadias syndrome, hantavirus pulmonary syndrome, white matter hypoplasia-corpus callosum agenesis-intellectual disability syndrome, deafness-genital anomalies-metacarpal and metatarsal synostosis syndrome, hearing loss-familial salivary gland insensitivity to aldosterone syndrome, multiple synostoses syndrome, central nervous system calcification-deafness-tubular acidosis-anemia syndrome, multiple paragangliomas associated with polycythemia, syngnathia multiple anomalies, Takayasu arteritis, severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency, spondylocostal dysostosis-hypospadias-intellectual disability syndrome, hypotrichosis-deafness syndrome, thalidomide embryopathy, trisomy X, trisomy 13, trisomy 18, umbilical cord ulceration-intestinal atresia syndrome, microcephaly-brachydactyly-kyphoscoliosis syndrome, Waardenburg syndrome, Weill-Marchesani syndrome, infantile spasms, Wolfram syndrome, epidermal nevus syndrome, digital anomalies-intellectual disability-short stature syndrome, intellectual disability-obesity-brain malformations-facial dysmorphism syndrome, Erdheim-Chester disease, Stevens-Johnson syndrome, CADDS, finger hyperphalangy - toe anomalies - severe pectus excavatum syndrome, ataxia - telangiectasia variant, growth retardation-mild developmental delay-chronic hepatitis syndrome, primary microcephaly-mild intellectual disability-young-onset diabetes syndrome, ferro-cerebro-cutaneous syndrome, dystonia-aphonia syndrome, microcephaly-complex motor and sensory axonal neuropathy syndrome, X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome, severe intellectual disability-hypotonia-strabismus-coarse face-planovalgus syndrome, intrauterine growth restriction-short stature-early adult-onset diabetes syndrome, pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa, familial chylomicronemia syndrome, caudal regression-sirenomelia spectrum, visceral heterotaxy, Holmes-Adie syndrome, microcephalic primordial dwarfism due to RTTN deficiency, Joubert syndrome, congenital generalized hypercontractile muscle stiffness syndrome, Kallmann syndrome, Caroli syndrome, X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability, microlissencephaly-micromelia syndrome, branchiootic syndrome, Plummer-Vinson syndrome, Cushing syndrome, McCune-Albright syndrome, Meckel syndrome, SUNCT syndrome, mucopolysaccharidosis type 3, mucopolysaccharidosis type 4, congenital myasthenic syndrome, Loeys-Dietz syndrome, Alport syndrome, schisis association, Tolosa-Hunt syndrome, iridocorneal endothelial syndrome, Noonan syndrome, short fifth metacarpals-insulin resistance syndrome, progressive supranuclear palsy, benign exophthalmos syndrome, Sandifer syndrome, global developmental delay-osteopenia-ectodermal defect syndrome, tubular renal disease-cardiomyopathy syndrome, angioosteohypotrophic syndrome, 6q terminal deletion syndrome, Axenfeld-Rieger syndrome, peroxisome biogenesis disorder, ectodermal dysplasia syndrome, Seckel syndrome, Sotos syndrome, Stickler syndrome, pelvis syndrome, Susac syndrome, ischio-vertebral syndrome, BRESEK syndrome, Turner syndrome, Usher syndrome, obesity-colitis-hypothyroidism-cardiac hypertrophy-developmental delay syndrome, CREST syndrome, Sheehan syndrome, polymyalgia rheumatica, autoinflammatory syndrome, neuroleptic malignant syndrome, pituitary stalk interruption syndrome, monosomy 13q34, ring chromosome 13, 48,XXXY syndrome, 49,XXXXY syndrome, hereditary continuous muscle fiber activity, Eisenmenger syndrome, Robinow syndrome, Ehlers-Danlos syndrome, hypoplastic right heart syndrome, shone complex, 48,XYYY syndrome, subcortical band heterotopia, complex regional pain syndrome type 2, faciodigitogenital syndrome, neoplastic syndrome, paraneoplastic syndrome, post-infectious syndrome, Achard-Thiers syndrome, acral dysostosis dyserythropoiesis syndrome, agnathia-microstomia-synotia, Aksu von Stockhausen syndrome, Aloi Tomasini Isaia syndrome, temporomandibular joint dysfunction syndrome, Apert-like polydactyly syndrome, arakawa syndrome 2, arena syndrome, Arnold stickler bourne syndrome, baetz-greenwalt syndrome, bagatelle Cassidy syndrome, baker Vinters syndrome, bobble-head doll syndrome, Boerhaave syndrome, Cantu Sanchez-Corona Fragoso syndrome, Cantu Sanchez-Corona Hernandez syndrome, carbon baby syndrome, Carnevale hernandez castillo syndrome, Cartwright Nelson Fryns syndrome, Charles bonnet syndrome, Parinaud syndrome, corticobasal degeneration disorder, hair defect with photosensitivity and intellectual disability syndrome, AIDS dysmorphic syndrome, congenital acardia, acute lymphoblastic leukemia congenital sporadic aniridia, aglossia and situs inversus, agyria pachygyria polymicrogyria, agyria-pachygyria type 1, Ahumada Del Castillo syndrome, alopecia congenita keratosis palmoplantaris, alpha-mannosidosis type 1, aluminosis, Mauriac syndrome, ankle defects short stature, ankyloblepharon filiforme imperforate anus, annular constricting bands, anophthalmia cleft palate micrognathia, anophthalmia esophageal atresia cryptorchidism, anotia facial palsy cardiac defect, aortic dissection lentiginosis, childhood aortic valve stenosis, arthrogryposis IUGR thoracic dystrophy, arthrogryposis multiplex congenita CNS calcification, arthrogryposis spinal muscular atrophy, asternia, atlanto-axial fusion, atrophoderma of Pierini and Pasini, Barnicoat Baraitser syndrome, Basedow’s coma, BD syndrome, Beardwell syndrome, bhaskar jagannathan syndrome, bidirectional tachycardia, bilirubin induced brain injury in the newborn, blepharo naso facial syndrome van Maldergem type, bone dysplasia corpus callosum agenesis, brachydactyly absence of distal phalanges, brachydactyly anonychia, brachydactyly small stature face anomalies, brachydactyly tibial hypoplasia, brittle bone syndrome lethal type, bronchiectasis oligospermia, Brunsting-Perry syndrome, bruyn scheltens syndrome, burn goodship syndrome, camptodactyly joint contractures and facial skeletal dysplasia, camptodactyly vertebral fusion, Cantu Sanchez-Corona Garcia-Cruz syndrome, cardiac hydatid cysts with intracavitary expansion, cardioencephalomyopathy, cardiofacial syndrome short limbs, cardiomelic syndrome stratton Koehler type, cardiomyopathy and deafness due to tRNA lysine gene mutation, cardiomyopathy diabetes deafness, cardiomyopathy hypogonadism collagenoma syndrome, cardiomyopathy hypogonadism metabolic anomalies, cardiomyopathy spherocytosis, carpo tarsal osteolysis recessive, autosomal dominant cataract, cataract skeletal anomalies, cennamo gangemi syndrome, cerebellar agenesis, cerebello-olivary atrophy, cerebral calcification cerebellar hypoplasia, cerebral calcifications opalescent teeth phosphaturia, oculo digital syndrome, chondrodysplasia, choreoacanthocytosis amyotrophic, chorioretinopathy dominant form microcephaly, Christian Demyer Franken syndrome, Christian Johnson angenieta syndrome, chromosome 3 duplication syndrome, chronic demyelinizing neuropathy with IgM monoclonal, ciliary dyskinesia-bronchiectasis, circumscribed cutaneous aplasia of the vertex, circumscribed disseminated keratosis Jadassohn lew type, cleft lip and palate malrotation cardiopathy, cleft lip and/or palate with mucous cysts of lower, cleft lip palate dysmorphism kumar type, cleft lip palate intellectual disability corneal opacity, cleft lip palate oligodontia syndactyly pili torti, cleft lip palate pituitary deficiency, cleft lip palate-tetraphocomelia, cleft lower lip cleft lateral canthi chorioretinal, cleft palate cardiac defect ectrodactyly, cleft palate colobomata radial synostosis deafness, cleft palate heart disease polydactyly absent tibia, cleft tongue, coarse face hypotonia constipation, Cohen Lockood Wyborney syndrome, type 2 collagenopathy, Collins-Sakati syndrome, coloboma porencephaly hydronephrosis, colobomata unilobar lung heart defect, colonic malakoplakia, Colver Steer Godman syndrome, Combarros Calleja Leno syndrome, complement receptor deficiency, congenital absence of the sternocleidomastoid muscle, congenital amputation, congenital aneurysms of the great vessels, congenital articular rigidity, congenital benign spinal muscular atrophy dominant, congenital cardiovascular shunt, congenital contractures, congenital craniosynostosis maternal hyperthyroiditis, congenital cystic eye, congenital heart disease ptosis hypodontia craniostosis, congenital heart disease radio ulnar synostosis intellectual disability, congenital mumps, congenital stenosis of cervical medullary canal, Dennis-Fairhurst-Moore syndrome, congenital unilateral pulmonary hypoplasia, congenital vagal hyperreflexivity, Cormier Rustin Munnich syndrome, corneal crystals myopathy neuropathy, corneal dystrophy ichthyosis microcephaly intellectual disability, corneal dystrophy pigmentary anomaly malabsorption, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cortada Koussef Matsumoto syndrome, Cortes Lacassie syndrome, craniofacial and skeletal defects, craniofacial dysostosis arthrogryposis progeroid appearance, craniofrontonasal syndrome Teebi type, craniostenosis with congenital heart disease intellectual disability, crawfurd syndrome, cutis gyratum acanthosis nigricans craniosynostosis, cutis laxa osteoporosis, Davenport-Donlan syndrome, Davis Lafer syndrome, de Hauwere Leroy adriaenssens syndrome, deafness conductive stapedial ear malformation facial palsy, deafness goiter stippled epiphyses, deafness hypospadias metacarpal and metatarsal syndrome, deafness mesenteric diverticula of small bowel neuropathy, deafness peripheral neuropathy arterial disease, deafness progressive cataract autosomal dominant, dermatocardioskeletal syndrome boronne type, dextrocardia with situs inversus, diabetes persistent mullerian ducts, diaphragmatic agenesis radial aplasia omphalocele, diaphragmatic hernia exomphalos corpus callosum agenesis, diaphragmatic hernia upper limb defects, die Smulders droog van dijk syndrome, diomedi bernardi placidi syndrome, diphallus rachischisis imperforate anus, distichiasis heart congenital anomalies, double discordia, double uterus-hemivagina-renal agenesis, Drachtman Weinblatt Sitarz syndrome, Duker-Weiss-Siber syndrome, duodenal atresia tetralogy of fallot, duplication of leg mirror foot, duplication of the thumb unilateral biphalangeal, dupont sellier chochillon syndrome, dwarfism bluish sclerae, dwarfism deafness retinitis pigmentosa, dwarfism lethal type advanced bone age, dwarfism thin bones multiple fractures, dysmorphism cleft palate loose skin, Eagle syndrome, ectrodactyly cardiopathy dysmorphism, Elliott ludman Teebi syndrome, enamel hypoplasia cataract hydrocephaly, encephalocele anencephaly, enchondromatosis dwarfism deafness, Engelhard Yatziv syndrome, enlarged vestibular aqueduct syndrome, epidermal nevus vitamin D resistant rickets, epimetaphyseal dysplasia cataract, epiphyseal dysplasia dysmorphism camptodactyly, esophageal atresia coloboma talipes, extrasystoles short stature hyperpigmentation microcephaly, facial clefting corpus callosum agenesis, facio digito genital syndrome recessive form, facio skeletal genital syndrome rippberger type, familial capillaro-venous leptomeningeal angiomatosis, Dursun syndrome, Faye-Petersen-Ward-Carey syndrome, feigenbaum Bergeron syndrome, Feingold trainer syndrome, fetal brain disruption sequence, fetal enterovirus syndrome, fetal parainfluenza virus type 3 syndrome, fetal phenothiazine syndrome, fibromatosis multiple non ossifying, fibula aplasia complex brachydactyly, fibular hypoplasia scapulo pelvic dysplasia absent, Fitz-Hugh-Curtis syndrome, focal alopecia congenital megalencephaly, focal or multifocal malformations in neuronal migration, foix chavany Marie syndrome, Fontaine farriaux blanckaert syndrome, Fraser Jequier Chen syndrome, Freiberg disease, Friedman Goodman syndrome, frontonasal malformation cloacal exstrophy, frontonasal dysplasia Klippel feil syndrome, frontonasal dysplasia phocomelic upper limbs, Fryns Fabry Remans syndrome, Fryns Smeets Thiry syndrome, Fuchs atrophia gyrata chorioideae et retinae, Fukuda-Miyanomae-Nakata syndrome, Fuqua Berkovitz syndrome, Garret-Tripp syndrome, gas bloat syndrome, Gaucher ichthyosis restrictive dermopathy, gershinibaruch Leibo syndrome, Ghose-Sachdev-Kumar syndrome, gigantism advanced bone age hoarse cry, glossopalatine ankylosis micrognathia ear anomalies, goldstein hutt syndrome, goniodysgenesis intellectual disability short stature, green sandford davison syndrome, grix Blankenship Peterson syndrome, Ho-Kaufman-McAlister syndrome, Jaffer-Beighton syndrome, Judge Misch wright syndrome, Kashani-Strom-Utley syndrome, Kasznica-Carlson-Coppedge syndrome, Katsantoni-Papadakou-Lagoyanni syndrome, Kocher-debre-Semelaigne syndrome, Koone-Rizzo-Elias syndrome, Kozlowski Brown Hardwick syndrome, Kozlowski Ouvrier syndrome, Kozlowski Rafinski Klicharska syndrome, Kozlowski Warren Fisher syndrome, Krauss Herman Holmes syndrome, Krieble Bixler syndrome, Kuster Majewski Hammerstein syndrome, Kuster syndrome, Laugier-Hunziker syndrome, Laurence-Prosser-Rocker syndrome, le Marec-Bracq-Picaud syndrome, levator syndrome, Marinesco-Sjogren-like syndrome, Milner-Khallouf-Gibson syndrome, radio-digito-facial dysplasia, Seckel like syndrome majoor-krakauer type, neonatal aspiration syndrome, muscular fibrosis multifocal obstructed vessels, short stature contractures hypotonia, Alice in Wonderland syndrome, megacystis-microcolon-intestinal hypoperistalsis syndrome, Basilicata-Akhtar syndrome, Liberfarb syndrome, craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome, cardiac, facial, and digital anomalies with developmental delay, fibrosis, neurodegeneration, and cerebral angiomatosis, Duane anomaly-myopathy-scoliosis syndrome, congenital cataract-severe neonatal hepatopathy-global developmental delay syndrome, infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome, acute radiation syndrome, monoclonal mast cell activation syndrome, oculocerebrodental syndrome, syndromic congenital sodium diarrhea, congenital brachyesophagus-intrathoracic stomach-vertebral anomalies syndrome, intellectual disability-cardiac anomalies-short stature-joint laxity syndrome, intrauterine growth restriction-congenital multiple café-au-lait macules-increased sister chromatid exchange syndrome, frontonasal dysplasia-bifid nose-upper limb anomalies syndrome, microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome, diaphragmatic hernia-short bowel-asplenia syndrome, warts-immunodeficiency-lymphedema-anogenital dysplasia syndrome, Cramp-fasciculation syndrome, choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome, blepharophimosis-intellectual disability syndrome/genitopatellar overlap syndrome, CCNK-related neurodevelopmental disorder-severe intellectual disability-facial dysmorphism syndrome, cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome, KLHL7-related Bohring-Opitz-like syndrome, KLHL7-related cold-induced sweating-like syndrome, KAT6B-related multiple congenital anomalies syndrome, oculogastrointestinal-neurodevelopmental syndrome, spastic paraparesis-cataracts-speech delay syndrome, Ruzicka-Goerz-Anton syndrome, Sammartino-Decreccio syndrome, Samson-Gardner syndrome, Samson-Viljoen syndrome, Sanderson-Fraser syndrome, Sandhaus-Ben-Ami syndrome, prostatic malacoplakia associated with prostatic abscess, Saul-Wilkes-Stevenson syndrome, macrogyria, pseudobulbar palsy and intellectual disability, Schwartz-Cohen-addad-Lambert syndrome, Schlegelberger-Grote syndrome, Schrander-stumpel-Theunissen-Hulsmans syndrome, Saal-Bulas syndrome, Sackey-Sakati-Aur syndrome, Slti-Salem syndrome, Zerres Rietschel Majewski syndrome, Zazam Sheriff Phillips syndrome, Zadik-Barak-Levin syndrome, weinstein kliman scully syndrome, thickened earlobes with conductive deafness from incus-stapes abnormalities, ichthyosis linearis circumflexa, infantile striato thalamic degeneration, Landy-Donnai syndrome, merlob grunebaum reisner syndrome, Pavone Fiumara Rizzo syndrome, pfeiffer rockelein syndrome, Pfeiffer Tietze Welte syndrome, phosphoribosylpyrophosphate synthetase deficiency, piepkorn karp hickok syndrome, podder-tolmie syndrome, pointer syndrome, richieri-costa guion-almeida cohen syndrome, Rubinstein Taybi like syndrome, ruvalcaba churesigaew myhre syndrome, short limb dwarf lethal colavita kozlowski type, Mallory-Weiss syndrome, superior vena cava syndrome, piriformis syndrome, engraftment syndrome, Adams-Stokes syndrome, Leriche syndrome, multiple organ dysfunction syndrome, posterior leukoencephalopathy syndrome, cardio-renal syndrome, Rahman syndrome, X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome, retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, Lopes-Maciel-Rodan syndrome, Stankiewicz-Isidor syndrome, Skraban-Deardorff syndrome, joint laxity, short stature, and myopia, Sweeney-Cox syndrome, Alkuraya-Kucinskas syndrome, Jaberi-Elahi syndrome, neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, hearing impairment and infertile male syndrome, cardiocutaneous syndrome, neonatal diabetes, congenital sensorineural hearing loss and congenital cataracts, cardioectodermal syndrome, cannabinoid hyperemesis syndrome, retrograde cricopharyngeus dysfunction, Zinner syndrome, retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome, IFAP syndrome, DICER1-related tumor predisposition, Roberts-SC phocomelia syndrome, carcinoid syndrome, Bonnevie-Ullrich syndrome, NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, RNU4ATAC spectrum disorder, syndromic congenital heart disease, hand-foot syndrome, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, gastrointestinal defects and immunodeficiency syndrome 1, achalasia-alacrima syndrome, black locks with albinism and deafness syndrome, Birt-Hogg-Dube syndrome, trigeminal trophic syndrome, developmental and/or epileptic encephalopathy with spike-wave activation in sleep, syndromic microspherophakia, painful legs and moving toes syndrome, congenital aphakia-iris hypoplasia-microphthalmia-microcornea syndrome, hereditary persistence of fetal hemoglobin-intellectual disability syndrome, developmental delay-immunodeficiency-leukoencephalopathy-hypohomocysteinemia syndrome, primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome, post-cardiac arrest syndrome, early-onset obesity-hyperphagia-severe developmental delay syndrome, hereditary alpha tryptasemia syndrome, KINSSHIP syndrome, developmental delay, hypotrophy, and dysmorphic features without moebius syndrome, breast implant illness, cataracts, hearing impairment, nephrotic syndrome, and enterocolitis, craniosynostosis-facial dysmorphism-chiari-1 malformation-developmental and language delay syndrome, MYT1L-related developmental delay-intellectual disability-obesity syndrome, Houge-Janssens syndrome, xerosis and growth failure with immune and pulmonary dysfunction syndrome, Fliedner-Zweier syndrome, Lui-Jee-Baron syndrome, Long-Olsen-Distelmaier syndrome, Tan-Almurshedi syndrome, diabetes, deafness, developmental delay, and short stature syndrome, Alfadhel syndrome, Hoxha-Aliu syndrome, cleft palate-congenital heart defect-intellectual disability syndrome, congenital insensitivity to pain syndrome, Marsili type, Yuksel-Vogel-Bauer syndrome, polydactyly-macrocephaly syndrome, pyoderma gangrenosum-acne-hidradenitis suppurativa-ankylosing spondylitis syndrome, psoriatic arthritis-pyoderma gangrenosum-acne-hidradenitis suppurativa syndrome, megalencephaly-polydactyly syndrome, Leigh syndrome, mitochondrial, auroneurodental syndrome, orofacial clefting-cardiac anomalies-facial dysmorphism syndrome, Grisel syndrome, arterial tortuosity-bone fragility syndrome, dialysis disequilibrium syndrome, brain abnormalities-severe developmental delay-facial dysmorphism-intellectual disability syndrome due to MEF2C mutation, Kariminejad neurodevelopmental syndrome, myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities, brain malformation renal syndrome, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2, Karayol-Borroto-Haghshenas neurodevelopmental syndrome, neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, Morimoto-Ryu-Malicdan neuromuscular syndrome, neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, neurodevelopmental disorder with variable familial hypercholanemia, Pan-Chung-Bellen syndrome, telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature, Muggenthaler-Chowdhury-Chioza syndrome, Tayoun-Maawali syndrome, ragopathy, cardiovascular-kidney-metabolic syndrome, craniofaciocardiohepatic syndrome, FICUS syndrome, Li-Takada-Miyake syndrome, Guillouet-Gordon syndrome, ICHAD syndrome, cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome, RAC2-related combined immunodeficiency-bronchiectasis-cancer-predisposing syndrome, oculovertebral syndrome, Alsahan-Harris syndrome, Ververi-Brady syndrome, Dursun-Ozgul neurodevelopmental syndrome, immune dysregulation, neurodevelopmental defects, and colitis, Harel-Tora neurodevelopmental syndrome, Valence-Farazi cerebellar ataxia syndrome, dyschromatosis, ichthyosis, deafness, and atopic disease, Ramond-Elliott neurodevelopmental syndrome, STAD syndrome, craniosynostosis-scoliosis syndrome, loin pain hematuria syndrome, IRF6-related condition, linkeropathy, NDUFB11-related disorders, CRYAB-related myofibrillar myopathy-cataract-cardiomyopathy spectrum disorder, TSEN2-related neurodevelopmental disorder with or without thrombotic microangiopathy, antiphospholipid syndrome

Subtypes (1): familial long QT syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

415 uncertain significance, 75 likely benign, 61 conflicting classifications of pathogenicity, 31 pathogenic, 9 likely pathogenic, 5 pathogenic/likely pathogenic, 2 benign, 2 benign/likely benign

ClinVarVariant (HGVS)GeneClassificationReview
1065921NM_000219.6(KCNE1):c.1A>T (p.Met1Leu)KCNE1Pathogeniccriteria provided, single submitter
1001814NM_000238.4(KCNH2):c.1897A>C (p.Asn633His)KCNH2Pathogeniccriteria provided, single submitter
1058879NM_000238.4(KCNH2):c.1825_1830del (p.Asp609_Lys610del)KCNH2Pathogeniccriteria provided, single submitter
1068864NC_000007.13:g.(?150644406)(150644976_?)delKCNH2Pathogeniccriteria provided, single submitter
1068865NC_000007.13:g.(?150642447)(150656830_?)delKCNH2Pathogeniccriteria provided, single submitter
1068866NC_000007.13:g.(?150654369)(150656834_?)delKCNH2Pathogeniccriteria provided, single submitter
1068978NM_000238.4(KCNH2):c.2555del (p.Phe852fs)KCNH2Pathogeniccriteria provided, single submitter
1069284NM_000238.4(KCNH2):c.1420_1472del (p.Thr474fs)KCNH2Pathogeniccriteria provided, single submitter
1069329NM_000238.4(KCNH2):c.544_556del (p.Ser182fs)KCNH2Pathogeniccriteria provided, single submitter
1070208NM_000238.4(KCNH2):c.221_242del (p.Thr74fs)KCNH2Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1070517NM_000238.4(KCNH2):c.669del (p.Leu225fs)KCNH2Pathogeniccriteria provided, single submitter
1070541NM_000238.4(KCNH2):c.3086_3099del (p.Ser1029fs)KCNH2Pathogeniccriteria provided, single submitter
1070567NM_000238.4(KCNH2):c.1707_1711dup (p.Ile571fs)KCNH2Pathogeniccriteria provided, single submitter
1072040NM_000238.4(KCNH2):c.3097_3106dup (p.Gly1036fs)KCNH2Pathogeniccriteria provided, single submitter
1072580NM_000238.4(KCNH2):c.2676_2680dup (p.Arg894fs)KCNH2Pathogeniccriteria provided, single submitter
1072804NM_000238.4(KCNH2):c.955_956del (p.Thr319fs)KCNH2Pathogeniccriteria provided, single submitter
1073738NM_000238.4(KCNH2):c.2931_2932insCTGGAGGCCCTTCTCCAGCCCCAGGCCCCCCGGAGAGCCGCCGGGTGGGGAGCCCCTGATGGAGGACTGC (p.Glu978fs)KCNH2Pathogeniccriteria provided, single submitter
1074304NM_000238.4(KCNH2):c.3101_3108del (p.Pro1034fs)KCNH2Pathogeniccriteria provided, multiple submitters, no conflicts
1074305NM_000238.4(KCNH2):c.2775del (p.Pro926fs)KCNH2Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1076264NM_000238.4(KCNH2):c.3255dup (p.Pro1086fs)KCNH2Pathogeniccriteria provided, single submitter
1076382NM_000238.4(KCNH2):c.817C>T (p.Arg273Ter)KCNH2Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1076538NM_000238.4(KCNH2):c.2682_2685dup (p.Asp896fs)KCNH2Pathogeniccriteria provided, single submitter
1076966NM_000238.4(KCNH2):c.893del (p.Pro298fs)KCNH2Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1018501NM_000218.3(KCNQ1):c.1559T>C (p.Met520Thr)KCNQ1Pathogeniccriteria provided, single submitter
1066272NM_000218.3(KCNQ1):c.1394-1G>CKCNQ1Pathogeniccriteria provided, multiple submitters, no conflicts
1068919NM_000218.3(KCNQ1):c.1344dup (p.Glu449fs)KCNQ1Pathogeniccriteria provided, multiple submitters, no conflicts
1069232NM_000218.3(KCNQ1):c.1730C>G (p.Ser577Ter)KCNQ1Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1072801NM_000218.3(KCNQ1):c.160_175del (p.Ile54fs)KCNQ1Pathogeniccriteria provided, single submitter
1074347NM_000218.3(KCNQ1):c.359G>A (p.Trp120Ter)KCNQ1Pathogeniccriteria provided, single submitter
1074799NC_000011.9:g.(?2797170)(2798282_?)delKCNQ1Pathogeniccriteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 130 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

GeneClassificationInheritanceDiseaseRecords
RNF207LimitedAutosomal dominantlong QT syndrome

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
RYR1Orphanet:169186Autosomal recessive centronuclear myopathy
RYR1Orphanet:169189Autosomal dominant centronuclear myopathy
RYR1Orphanet:178145Moderate multiminicore disease with hand involvement
RYR1Orphanet:324581Benign Samaritan congenital myopathy
RYR1Orphanet:33108Lethal multiple pterygium syndrome
RYR1Orphanet:423Malignant hyperthermia of anesthesia
RYR1Orphanet:424107Congenital myopathy with myasthenic-like onset
RYR1Orphanet:466650Exercise-induced malignant hyperthermia
RYR1Orphanet:597Central core disease
RYR1Orphanet:700188Calf-predominant weakness-gastrocnemius medialis atrophy-distal myopathy
RYR1Orphanet:98905Congenital multicore myopathy with external ophthalmoplegia
RYR1Orphanet:99741King-Denborough syndrome
RYR2Orphanet:293888Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
RYR2Orphanet:293899Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
RYR2Orphanet:293910Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
RYR2Orphanet:3286Catecholaminergic polymorphic ventricular tachycardia
SCN1BOrphanet:130Brugada syndrome
SCN1BOrphanet:1934Early infantile developmental and epileptic encephalopathy
SCN1BOrphanet:33069Dravet syndrome
SCN1BOrphanet:334Hereditary atrial fibrillation
SCN1BOrphanet:36387Genetic epilepsy with febrile seizure plus
SCN1BOrphanet:871Hereditary progressive cardiac conduction defect
SCN4AOrphanet:681Hypokalemic periodic paralysis
SCN4AOrphanet:682Hyperkalemic periodic paralysis
SCN4AOrphanet:684Paramyotonia congenita of Von Eulenburg
SCN4AOrphanet:98913Postsynaptic congenital myasthenic syndrome
SCN4AOrphanet:99734Myotonia fluctuans
SCN4AOrphanet:99735Myotonia permanens
SCN4AOrphanet:99736Acetazolamide-responsive myotonia
SCN5AOrphanet:101016Romano-Ward syndrome
SCN5AOrphanet:130Brugada syndrome
SCN5AOrphanet:1344Isolated atrial standstill
SCN5AOrphanet:154Familial isolated dilated cardiomyopathy
SCN5AOrphanet:166282Hereditary sick sinus syndrome
SCN5AOrphanet:228140Idiopathic ventricular fibrillation
SCN5AOrphanet:334Hereditary atrial fibrillation
SCN5AOrphanet:871Hereditary progressive cardiac conduction defect
SLC6A2Orphanet:443236Postural orthostatic tachycardia syndrome due to NET deficiency
SNTA1Orphanet:101016Romano-Ward syndrome
SYKOrphanet:695807Immunodeficiency-systemic inflammation-lymphoma predisposition syndrome
TCAPOrphanet:154Familial isolated dilated cardiomyopathy
TCAPOrphanet:34514Telethonin-related limb-girdle muscular dystrophy R7
TGFB3Orphanet:293888Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
TGFB3Orphanet:293899Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
TGFB3Orphanet:293910Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
TGFB3Orphanet:60030Loeys-Dietz syndrome
TGFB3Orphanet:91387Familial thoracic aortic aneurysm and aortic dissection
TMPOOrphanet:154Familial isolated dilated cardiomyopathy
TNNI3Orphanet:154Familial isolated dilated cardiomyopathy
TNNI3Orphanet:75249Familial isolated restrictive cardiomyopathy

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence75

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
RNF207HGNC:32947ENSG00000158286Q6ZRF8RING finger protein 207gencc,clinvar
RHEBHGNC:10011ENSG00000106615Q15382GTP-binding protein Rhebclinvar
RYR1HGNC:10483ENSG00000196218P21817Ryanodine receptor 1clinvar
RYR2HGNC:10484ENSG00000198626Q92736Ryanodine receptor 2clinvar
SCN1BHGNC:10586ENSG00000105711Q07699Sodium channel regulatory subunit beta-1clinvar
SCN4AHGNC:10591ENSG00000007314P35499Sodium channel protein type 4 subunit alphaclinvar
SCN5AHGNC:10593ENSG00000183873Q14524Sodium channel protein type 5 subunit alphaclinvar
SDC1HGNC:10658ENSG00000115884P18827Syndecan-1clinvar
SLC2A5HGNC:11010ENSG00000142583P22732Solute carrier family 2, facilitated glucose transporter member 5clinvar
SLC6A2HGNC:11048ENSG00000103546P23975Sodium-dependent noradrenaline transporterclinvar
SNAPC4HGNC:11137ENSG00000165684Q5SXM2snRNA-activating protein complex subunit 4clinvar
SNTA1HGNC:11167ENSG00000101400Q13424Alpha-1-syntrophinclinvar
SYKHGNC:11491ENSG00000165025P43405Tyrosine-protein kinase SYKclinvar
TCAPHGNC:11610ENSG00000173991O15273Telethoninclinvar
TGFB3HGNC:11769ENSG00000119699P10600Transforming growth factor beta-3 proproteinclinvar
TMPOHGNC:11875ENSG00000120802P42166Lamina-associated polypeptide 2, isoform alphaclinvar
TNFRSF6BHGNC:11921ENSG00000243509O95407Tumor necrosis factor receptor superfamily member 6Bclinvar
TNNI3HGNC:11947ENSG00000129991P19429Troponin I, cardiac muscleclinvar
TOP2AHGNC:11989ENSG00000131747P11388DNA topoisomerase 2-alphaclinvar
TTNHGNC:12403ENSG00000155657Q8WZ42Titinclinvar
UPP1HGNC:12576ENSG00000183696Q16831Uridine phosphorylase 1clinvar
USP19HGNC:12617ENSG00000172046O94966Ubiquitin carboxyl-terminal hydrolase 19clinvar
VCLHGNC:12665ENSG00000035403P18206Vinculinclinvar
VSX1HGNC:12723ENSG00000100987Q9NZR4Visual system homeobox 1clinvar
YME1L1HGNC:12843ENSG00000136758Q96TA2ATP-dependent zinc metalloprotease YME1L1clinvar
ZNF174HGNC:12963ENSG00000103343Q15697Zinc finger protein 174clinvar
TLNRD1HGNC:13519ENSG00000140406Q9H1K6Talin rod domain-containing protein 1clinvar
CACNA1CHGNC:1390ENSG00000151067Q13936Voltage-dependent L-type calcium channel subunit alpha-1Cclinvar
CACNA1DHGNC:1391ENSG00000157388Q01668Voltage-dependent L-type calcium channel subunit alpha-1Dclinvar
CACNA1SHGNC:1397ENSG00000081248Q13698Voltage-dependent L-type calcium channel subunit alpha-1Sclinvar
CACNA2D1HGNC:1399ENSG00000153956P54289Voltage-dependent calcium channel subunit alpha-2/delta-1clinvar
CACNB2HGNC:1402ENSG00000165995Q08289Voltage-dependent L-type calcium channel subunit beta-2clinvar
JPH2HGNC:14202ENSG00000149596Q9BR39Junctophilin-2clinvar
STK32BHGNC:14217ENSG00000152953Q9NY57Serine/threonine-protein kinase 32Bclinvar
SHANK3HGNC:14294ENSG00000251322Q9BYB0SH3 and multiple ankyrin repeat domains protein 3clinvar
CALM1HGNC:1442ENSG00000198668P0DP23Calmodulin-1clinvar
CALM2HGNC:1445ENSG00000143933P0DP24Calmodulin-2clinvar
NET1HGNC:14592ENSG00000173848Q7Z628Neuroepithelial cell-transforming gene 1 proteinclinvar
CRELD1HGNC:14630ENSG00000163703Q96HD1Protein disulfide isomerase CRELD1clinvar
SIRT6HGNC:14934ENSG00000077463Q8N6T7NAD-dependent protein deacylase sirtuin-6clinvar
CASQ2HGNC:1513ENSG00000118729O14958Calsequestrin-2clinvar
CAV3HGNC:1529ENSG00000182533P56539Caveolin-3clinvar
SNAPC5HGNC:15484ENSG00000174446O75971snRNA-activating protein complex subunit 5clinvar
LDB3HGNC:15710ENSG00000122367O75112LIM domain-binding protein 3clinvar
ANKRD1HGNC:15819ENSG00000148677Q15327Ankyrin repeat domain-containing protein 1clinvar
REM1HGNC:15922ENSG00000088320O75628GTP-binding protein REM 1clinvar
ZNF341HGNC:15992ENSG00000131061Q9BYN7Zinc finger protein 341clinvar
MYLK2HGNC:16243ENSG00000101306Q9H1R3Myosin light chain kinase 2, skeletal/cardiac muscleclinvar
ACTN2HGNC:164ENSG00000077522P35609Alpha-actinin-2clinvar
SLMAPHGNC:16643ENSG00000163681Q14BN4Sarcolemmal membrane-associated proteinclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
RNF207RING finger protein 207Plays a role in cardiac repolarization possibly by stabilizing membrane expression of the potassium channel KCNH2/HERG, or by assisting its synthesis, folding or export from the endoplasmic reticulum, in a heat shock protein-dependent mann…
RHEBGTP-binding protein RhebSmall GTPase that acts as an allosteric activator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation…
RYR1Ryanodine receptor 1Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules.
RYR2Ryanodine receptor 2Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction.
SCN1BSodium channel regulatory subunit beta-1Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes.
SCN4ASodium channel protein type 4 subunit alphaPore-forming subunit of Nav1.4, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
SCN5ASodium channel protein type 5 subunit alphaPore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
SDC1Syndecan-1Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix.
SLC2A5Solute carrier family 2, facilitated glucose transporter member 5Functions as a fructose transporter that has only low activity with other monosaccharides.
SLC6A2Sodium-dependent noradrenaline transporterMediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline), the primary signaling neurotransmitter in the autonomic sympathetic nervous system.
SNAPC4snRNA-activating protein complex subunit 4Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes.
SNTA1Alpha-1-syntrophinAdapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins.
SYKTyrosine-protein kinase SYKNon-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR).
TCAPTelethoninMuscle assembly regulating factor.
TGFB3Transforming growth factor beta-3 proproteinTransforming growth factor beta-3 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains, which constitute the regulatory and active subunit of TGF-beta-3, respectively.
TMPOLamina-associated polypeptide 2, isoform alphaMay be involved in the structural organization of the nucleus and in the post-mitotic nuclear assembly.
TNFRSF6BTumor necrosis factor receptor superfamily member 6BDecoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL.
TNNI3Troponin I, cardiac muscleTroponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
TOP2ADNA topoisomerase 2-alphaKey decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken stra…
TTNTitinKey component in the assembly and functioning of vertebrate striated muscles.
UPP1Uridine phosphorylase 1Catalyzes the reversible phosphorylytic cleavage of uridine to uracil and ribose-1-phosphate which can then be utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.
USP19Ubiquitin carboxyl-terminal hydrolase 19Deubiquitinating enzyme that regulates the degradation of various proteins by removing ubiquitin moieties, thereby preventing their proteasomal degradation.
VCLVinculinActin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion.
VSX1Visual system homeobox 1Binds to the 37-bp core of the locus control region (LCR) of the red/green visual pigment gene cluster.
YME1L1ATP-dependent zinc metalloprotease YME1L1ATP-dependent metalloprotease that catalyzes the degradation of folded and unfolded proteins with a suitable degron sequence in the mitochondrial intermembrane region.
ZNF174Zinc finger protein 174Transcriptional repressor.
TLNRD1Talin rod domain-containing protein 1Actin-binding protein which may have an oncogenic function and regulates cell proliferation, migration and invasion in cancer cells.
CACNA1CVoltage-dependent L-type calcium channel subunit alpha-1CPore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents.
CACNA1DVoltage-dependent L-type calcium channel subunit alpha-1DVoltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
CACNA1SVoltage-dependent L-type calcium channel subunit alpha-1SPore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle.
CACNA2D1Voltage-dependent calcium channel subunit alpha-2/delta-1The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.
CACNB2Voltage-dependent L-type calcium channel subunit beta-2Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current.
JPH2Junctophilin-2Membrane-binding protein that provides a structural bridge between the plasma membrane and the sarcoplasmic reticulum and is required for normal excitation-contraction coupling in cardiomyocytes.
SHANK3SH3 and multiple ankyrin repeat domains protein 3Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance.
CALM1Calmodulin-1Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding.
CALM2Calmodulin-2Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding.
NET1Neuroepithelial cell-transforming gene 1 proteinActs as a guanine nucleotide exchange factor (GEF) for RhoA GTPase.
CRELD1Protein disulfide isomerase CRELD1Protein disulfide isomerase.
SIRT6NAD-dependent protein deacylase sirtuin-6NAD-dependent protein deacetylase, deacylase and mono-ADP-ribosyltransferase that plays an essential role in DNA damage repair, telomere maintenance, metabolic homeostasis, inflammation, tumorigenesis and aging.
CASQ2Calsequestrin-2Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle.
CAV3Caveolin-3May act as a scaffolding protein within caveolar membranes.
SNAPC5snRNA-activating protein complex subunit 5Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes.
LDB3LIM domain-binding protein 3May function as an adapter in striated muscle to couple protein kinase C-mediated signaling via its LIM domains to the cytoskeleton.
ANKRD1Ankyrin repeat domain-containing protein 1May play an important role in endothelial cell activation.
REM1GTP-binding protein REM 1Promotes endothelial cell sprouting and actin cytoskeletal reorganization.
ZNF341Zinc finger protein 341Transcriptional activator of STAT3 involved in the regulation of immune homeostasis.
MYLK2Myosin light chain kinase 2, skeletal/cardiac muscleImplicated in the level of global muscle contraction and cardiac function.
ACTN2Alpha-actinin-2F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures.
SLMAPSarcolemmal membrane-associated proteinAssociates with the striatin-interacting phosphatase and kinase (STRIPAK) core complex, forming the extended (SIKE1:SLMAP)STRIPAK complex.
UBR5E3 ubiquitin-protein ligase UBR5E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus.

Protein-family classification

Druggable: 28 · Difficult: 19 · Unknown: 28 · Druggable fraction: 0.37

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Ion channel913.4×2e-07
Scaffold/PPI92.1×0.143
Kinase62.2×0.178
Antibody/Immunoglobulin41.6×0.639
Protease31.5×0.673
Transcription factor101.1×0.707
Transporter11.0×0.888
Other/Unknown280.7×1.000
Enzyme (other)40.6×1.000
GPCR10.3×1.000

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
RNF207Transcription factornoZnf_B-box, Znf_RING, Znf_RING/FYVE/PHD
RHEBEnzyme (other)yes3.6.5.2Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
RYR1Ion channelyesRIH_dom, B30.2/SPRY, Ryanodine_rcpt
RYR2Ion channelyesRIH_dom, B30.2/SPRY, EF_hand_dom
SCN1BAntibody/ImmunoglobulinyesIg_V-set, Ig-like_fold, Na_channel_b1/b3
SCN4AIon channelyesNa_channel_asu, Ion_trans_dom, Na_channel_a4su_mammal
SCN5AIon channelyesNa_channel_asu, Ion_trans_dom, Na_channel_a5su
SDC1Other/UnknownnoSyndecan, Neurexin-like, Syndecan/Neurexin_dom
SLC2A5TransporteryesFru_transpt_5, Sugar/inositol_transpt, MFS_sugar_transport-like
SLC6A2Other/UnknownnoNa/ntran_symport, Na/ntran_symport_noradrenaline, SNS_sf
SNAPC4Transcription factornoSANT/Myb, Homeodomain-like_sf, SANT_dom
SNTA1Scaffold/PPInoPDZ, PH_domain, PH-like_dom_sf
SYKKinaseyes2.7.10.2Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
TCAPOther/UnknownnoTelethonin, Titin-like_dom_sf
TGFB3Other/UnknownnoTGF-b_propeptide, TGF-b_C, TGF-beta-like
TMPOOther/UnknownnoLEM_dom, LEM/LEM-like_dom_sf, LEM-like_dom
TNFRSF6BOther/UnknownnoTNFR/NGFR_Cys_rich_reg, TNFRSF6B_N, TNFRSF_decoy_receptor
TNNI3Other/UnknownnoTroponin, Troponin-I_N, Troponin_sf
TOP2AEnzyme (other)yes5.6.2.2TopoII_euk, Topo_IIA, Topo_IIA_dom_A
TTNKinaseyes2.7.11.1Prot_kinase_dom, Ig_sub2, Ig_sub
UPP1Enzyme (other)yes2.4.2.3Nucleoside_phosphorylase_d, Uridine_phosphorylase_euk, Nucleoside_phosphorylase_CS
USP19ProteaseyesPeptidase_C19_UCH, Znf_MYND, CS_dom
VCLOther/UnknownnoVinculin_CS, Vinculin/catenin, Vinculin
VSX1Transcription factornoHD, Homeodomain-like_sf, Homeobox_CS
YME1L1Proteaseyes3.4.24.B18Peptidase_M41, AAA+_ATPase, ATPase_AAA_core
ZNF174Transcription factornoSCAN_dom, Znf_C2H2_type, Znf_C2H2_sf
TLNRD1Other/UnknownnoTLNRD1, Talin_IBS2B
CACNA1CIon channelyesVDCCAlpha1, VDCC_L_a1su, VDCC_L_a1csu
CACNA1DIon channelyesVDCCAlpha1, VDCC_L_a1su, LVDCC_a1dsu
CACNA1SIon channelyesVDCCAlpha1, VDCC_L_a1su, VDCC_L_a1ssu
CACNA2D1Other/UnknownnoVWF_A, VWA_N, VDCC_a2/dsu
CACNB2Scaffold/PPInoVDCC_L_bsu, SH3_domain, VDCC_L_b2su
JPH2Other/UnknownnoMORN, Junctophilin
STK32BKinaseyesProt_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
SHANK3Scaffold/PPInoSH3_domain, PDZ, SAM
CALM1Other/UnknownnoEF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
CALM2Other/UnknownnoEF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
NET1Scaffold/PPInoDH_dom, GDS_CDC24_CS, PH_domain
CRELD1Other/UnknownnoEGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
SIRT6Enzyme (other)yes2.3.1.B41Sirtuin, Ssirtuin_cat_dom, DHS-like_NAD/FAD-binding_dom
CASQ2Other/UnknownnoCalsequestrin, Calsequestrin_CS, Thioredoxin-like_sf
CAV3Other/UnknownnoCaveolin, Caveolin_CS
SNAPC5Other/UnknownnoSNAPC5
LDB3Transcription factornoPDZ, Znf_LIM, Zasp-like_motif
ANKRD1Scaffold/PPInoAnkyrin_rpt, Ankyrin_rpt-contain_sf
REM1Other/UnknownnoSmall_GTPase, Small_GTP-bd, RGK
ZNF341Transcription factornoZnf_C2H2_type, Znf_C2H2_sf
MYLK2Kinaseyes2.7.11.18Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
ACTN2Other/UnknownnoActinin_actin-bd_CS, CH_dom, Spectrin_repeat
SLMAPOther/UnknownnoFHA_dom, SMAD_FHA_dom_sf, Cent_Immune-Sig_Mod

Expression context

Cohort genes with no expression data: 0.

65 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)75
unknown0

Top tissues across cohort

TissueCohort genes
apex of heart11
hindlimb stylopod muscle11
ventricular zone7
ganglionic eminence6
gastrocnemius6
skeletal muscle tissue of rectus abdominis6
secondary oocyte6
right hemisphere of cerebellum5
skeletal muscle tissue of biceps brachii5
cerebellar hemisphere5
right atrium auricular region4
left ventricle myocardium4
lower esophagus mucosa4
buccal mucosa cell4
endothelial cell4
cerebellar cortex4
male germ line stem cell (sensu Vertebrata) in testis4
middle temporal gyrus4
gluteal muscle3
heart right ventricle3

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
RNF207196broadmarkerapex of heart, right atrium auricular region, heart left ventricle
RHEB218ubiquitousmarkerventricular zone, embryo, ganglionic eminence
RYR1214broadmarkergluteal muscle, gastrocnemius, hindlimb stylopod muscle
RYR2210broadmarkerheart right ventricle, left ventricle myocardium, myocardium
SCN1B133ubiquitousmarkerprimary visual cortex, right hemisphere of cerebellum, cerebellum
SCN4A153tissue_specificyeshindlimb stylopod muscle, gastrocnemius, skeletal muscle tissue of rectus abdominis
SCN5A161broadyesapex of heart, heart left ventricle, cardiac ventricle
SDC1240ubiquitousmarkerlower esophagus mucosa, skin of abdomen, pharyngeal mucosa
SLC2A5231broadmarkerjejunal mucosa, duodenum, biceps brachii
SLC6A2121ubiquitousmarkerplacenta, buccal mucosa cell, decidua
SNAPC4249ubiquitousyessural nerve, endothelial cell, right uterine tube
SNTA1266ubiquitousmarkerapex of heart, hindlimb stylopod muscle, gastrocnemius
SYK239broadmarkermonocyte, mononuclear cell, leukocyte
TCAP213tissue_specificmarkerapex of heart, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis
TGFB3244broadmarkersaphenous vein, endocervix, gall bladder
TMPO287ubiquitousmarkerventricular zone, ganglionic eminence, embryo
TNFRSF6B127broadyesolfactory segment of nasal mucosa, spleen, subcutaneous adipose tissue
TNNI3169broadmarkerapex of heart, left ventricle myocardium, right atrium auricular region
TOP2A217ubiquitousmarkerventricular zone, ganglionic eminence, secondary oocyte
TTN223broadmarkerbiceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii
UPP1235ubiquitousmarkerlower esophagus mucosa, right hemisphere of cerebellum, cerebellar hemisphere
USP19275ubiquitousmarkergastrocnemius, hindlimb stylopod muscle, muscle of leg
VCL300ubiquitousmarkersaphenous vein, blood vessel layer, urethra
VSX1110tissue_specificmarkercerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum
YME1L1295ubiquitousmarkergerminal epithelium of ovary, tibia, parietal pleura
ZNF174206ubiquitousyesendothelial cell, male germ line stem cell (sensu Vertebrata) in testis, apex of heart
TLNRD1249ubiquitousmarkerileal mucosa, lower lobe of lung, cardiac muscle of right atrium
CACNA1C134broadmarkerapex of heart, right coronary artery, muscle layer of sigmoid colon
CACNA1D219broadmarkerbuccal mucosa cell, adrenal tissue, right lung
CACNA1S105tissue_specificmarkergluteal muscle, hindlimb stylopod muscle, triceps brachii

Protein interactions among cohort

Intra-cohort edges: 92.

Hub genes (top 10 by interactor count)

SymbolInteractor count
TOP2A7,587
SYK5,172
CIT5,077
VCL4,495
YME1L14,274
TTN4,237
UBR54,192
RHEB3,739
SHANK33,702
SIRT63,599

Intra-cohort edges

ABSources
ACTN2CACNA1Cbiogrid_interaction
ACTN2LDB3biogrid_interaction, intact, string_interaction
ACTN2MYPNbiogrid_interaction, string_interaction
ACTN2NEBLstring_interaction
ACTN2SHANK3biogrid_interaction
ACTN2TCAPstring_interaction
ACTN2TTNstring_interaction
ACTN2VCLstring_interaction
ANKRD1MYPNbiogrid_interaction, string_interaction
ANKRD1NEBLstring_interaction
ANKRD1TCAPstring_interaction
ANKRD1TTNbiogrid_interaction, string_interaction
CACNA1CCACNA1Sstring_interaction
CACNA1CCACNA2D1intact, string_interaction
CACNA1CCACNB2intact, string_interaction
CACNA1CCALM1intact
CACNA1CCASQ2string_interaction
CACNA1CCAV3string_interaction
CACNA1CHCN4string_interaction
CACNA1CJPH2string_interaction
CACNA1CREM1string_interaction
CACNA1CRYR2biogrid_interaction, string_interaction
CACNA1CSCN3Bstring_interaction
CACNA1DCACNA2D1string_interaction
CACNA1DCACNB2string_interaction
CACNA1DRYR2string_interaction
CACNA1DSHANK3intact
CACNA1SCACNA2D1string_interaction
CACNA1SCACNB2string_interaction
CACNA1SCAV3string_interaction
CACNA1SJPH2string_interaction
CACNA1SRYR1string_interaction
CACNA2D1CACNB2string_interaction
CACNA2D1RIMS1intact
CACNA2D1RYR1string_interaction
CACNA2D1SCN5Astring_interaction
CACNB2HCN4string_interaction
CACNB2SCN1Bstring_interaction
CACNB2SCN3Bstring_interaction
CACNB2SCN5Astring_interaction
CALM1RYR1biogrid_interaction
CALM1RYR2biogrid_interaction
CALM1SCN5Aintact
CALM1TNNI3intact
CASQ2JPH2string_interaction
CASQ2RYR2string_interaction
CASQ2SCN5Astring_interaction
CAV3JPH2string_interaction
CAV3SCN5Astring_interaction
CAV3SNTA1string_interaction

Structural data

PDB: 53 · AlphaFold-only: 22 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CALM1P0DP23337
SYKP4340593
TTNQ8WZ4264
SIRT6Q8N6T745
SCN1BQ0769939
TNNI3P1942939
VCLP1820637
SLC6A2P2397536
CACNA1CQ1393633
CACNA2D1P5428930
TRPM4Q8TD4329
RYR2Q9273626
ERAP1Q9NZ0823
CALM2P0DP2421
SNAPC4Q5SXM218
SCN5AQ1452416
ACTN2P3560916
RHEBQ1538215
TOP2AP1138815
TMPOP4216614
TGFB3P1060011
UBR5O9507111
TNFRSF6BO954078
HCN4Q9Y3Q48
CACNA1DQ016686
USP19O949665
SNAPC5O759715
CASQ2O149584
WDR26Q9H7D74
SCN4AP354993

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
HKDC1Q2TB9093.37
SLC2A5P2273290.35
CAV3P5653988.54
TGFBRAP1Q8WUH287.47
STK32BQ9NY5786.38
ANKRD1Q1532782.64
CRELD1Q96HD181.68
NLRP13Q86W2581.19
SNTA1Q1342480.00
DIP2AQ1468978.93
RNF207Q6ZRF876.18
UBR7Q8N80676.00
PKD1L2Q7Z44271.44
YME1L1Q96TA270.79
RALGAPA1Q6GYQ070.17
CITO1457869.75
WDR25Q64LD268.82
NOS1APO7505265.59
TDRD6O6052264.82
VSX1Q9NZR461.61
ZNF341Q9BYN757.11
MYPNQ86TC952.71

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 526. Enrichment computed across 169 evidence-associated genes (105 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 105 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Muscle contraction2316.9×1e-19RYR1, RYR2, SCN1B, SCN4A, SCN5A, TCAP, CACNA1C, CACNB2 (+15 more)
Cardiac conduction1717.6×1e-14RYR1, RYR2, SCN1B, SCN4A, SCN5A, CACNA1C, CACNB2, CALM1 (+9 more)
Phase 2 - plateau phase750.8×5e-09CACNA1C, CACNB2, AKAP9, KCNE1, KCNE2, KCNE3, KCNQ1
Phase 3 - rapid repolarisation665.3×1e-08AKAP9, KCNE1, KCNE2, KCNE3, KCNH2, KCNQ1
Striated Muscle Contraction823.5×1e-07TCAP, TNNI3, TTN, ACTN2, DMD, MYBPC3, MYH6, MYL3
Phase 0 - rapid depolarisation723.1×1e-06SCN1B, SCN4A, SCN5A, CACNA1C, CACNB2, CALM1, SCN3B
Interaction between L1 and Ankyrins517.5×6e-04SCN1B, SCN4A, SCN5A, SCN3B, ANK2
Adrenaline,noradrenaline inhibits insulin secretion415.0×0.009CACNA1C, CACNA1D, CACNB2, GNAI2
Ion homeostasis59.7×0.009RYR1, RYR2, TNNI3, CALM1, CASQ2
Inwardly rectifying K+ channels320.4×0.019KCNJ2, KCNJ5, KCNJ8
Signaling by BRAF and RAF1 fusions58.1×0.019VCL, CALM1, SND1, AKAP9, LMNA
NCAM signaling for neurite out-growth410.4×0.022CACNA1C, CACNA1D, CACNA1S, CACNB2
Non-integrin membrane-ECM interactions57.3×0.022SDC1, SNTA1, DMD, FGF2, LAMA4
Axon guidance93.9×0.022SCN1B, SCN4A, SCN5A, CACNA1C, CACNA1D, CACNA1S, CACNB2, SCN3B (+1 more)
NCAM1 interactions49.5×0.024CACNA1C, CACNA1D, CACNA1S, CACNB2
Oncogenic MAPK signaling49.5×0.024CALM1, SND1, AKAP9, LMNA
Sensory Perception65.4×0.024SCN1B, SDC1, CACNA1D, CACNB2, CALM1, KCNJ2
Nervous system development93.7×0.024SCN1B, SCN4A, SCN5A, CACNA1C, CACNA1D, CACNA1S, CACNB2, SCN3B (+1 more)
Potassium Channels56.4×0.030KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1
Glycogen metabolism236.2×0.031CALM1, GAA
Regulation of insulin secretion48.4×0.031CACNA1C, CACNA1D, CACNB2, GNAI2
Formation of the cornified envelope65.0×0.031DSC2, DSC3, DSG2, DSP, JUP, PKP2
L1CAM interactions55.7×0.041SCN1B, SCN4A, SCN5A, SCN3B, ANK2
Neuronal System83.4×0.056CACNB2, CALM1, ACTN2, KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1
CASP4 inflammasome assembly224.2×0.061CALM1, CALM2
G protein gated Potassium channels221.8×0.073KCNJ2, KCNJ5
Apoptotic cleavage of cell adhesion proteins219.8×0.085DSG2, DSP
Formation of the dystrophin-glycoprotein complex (DGC)38.8×0.088SNTA1, DMD, LAMA4
Regulation of CDH1 Function218.1×0.094VCL, JUP
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling216.7×0.107CALM1, ACTN2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 155 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
regulation of heart rate by cardiac conduction2458.0×8e-35SCN1B, SCN5A, CACNA1C, CACNA1D, CACNA2D1, CACNB2, HCN4, TRPM4 (+16 more)
cardiac muscle contraction1846.6×1e-23RYR2, SCN1B, SCN5A, TCAP, TNNI3, TTN, CASQ2, MYLK2 (+10 more)
ventricular cardiac muscle cell action potential1383.1×2e-21RYR2, SCN5A, SNTA1, CAV3, SCN3B, GPD1L, ANK2, KCNE1 (+5 more)
regulation of ventricular cardiac muscle cell membrane repolarization1370.7×5e-20SCN1B, SCN5A, SNTA1, CACNA2D1, CAV3, NOS1AP, AKAP9, ANK2 (+5 more)
regulation of heart rate1442.3×1e-17RYR2, SCN5A, SNTA1, CALM1, CALM2, CASQ2, CAV3, HCN4 (+6 more)
cardiac muscle cell action potential involved in contraction1149.8×1e-14SCN1B, SCN4A, SCN5A, CACNA1C, CACNA1D, CACNA2D1, SCN3B, KCNE1 (+3 more)
regulation of ventricular cardiac muscle cell action potential981.5×1e-14RYR2, CACNA1C, TRPM4, CTNNA3, DSC2, DSG2, DSP, JUP (+1 more)
regulation of cardiac muscle contraction845.8×5e-10RNF207, RYR2, CALM1, CALM2, CAV3, HCN4, NKX2-5, ANK2
bundle of His cell-Purkinje myocyte adhesion involved in cell communication693.2×5e-10CTNNA3, DSC2, DSG2, DSP, JUP, PKP2
membrane depolarization during cardiac muscle cell action potential763.4×5e-10SCN1B, SCN5A, CACNA1C, CACNA1D, HCN4, SCN3B, KCNJ2
striated muscle contraction843.5×5e-10RYR1, RYR2, TTN, CACNA1S, CASQ2, MYLK2, MYH6, MYH7
membrane repolarization during action potential665.2×1e-08KCNE1, KCNE2, KCNE3, KCNH2, KCNJ2, KCNQ1
membrane repolarization during ventricular cardiac muscle cell action potential665.2×1e-08KCNE1, KCNE2, KCNE3, KCNH2, KCNJ8, KCNQ1
muscle contraction1114.8×2e-08RYR1, SCN4A, SNTA1, TTN, CACNA1S, SLMAP, HCN4, MYH6 (+3 more)
regulation of membrane repolarization650.2×7e-08CASQ2, AKAP9, KCNE2, KCNH2, KCNJ2, KCNQ1
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion730.4×2e-07RYR2, CACNA1C, CALM1, CALM2, CASQ2, DMD, ANK2
regulation of sodium ion transmembrane transport640.8×3e-07SCN1B, SCN5A, SNTA1, CAV3, SLMAP, DMD
sarcomere organization819.8×4e-07TCAP, TTN, LDB3, ANKRD1, ACTN2, MYPN, MYBPC3, MYH6
positive regulation of sodium ion transport632.6×1e-06SCN1B, SCN5A, SCN3B, NKX2-5, GPD1L, PKP2
membrane depolarization during AV node cell action potential487.0×2e-06SCN5A, CACNA1C, CACNB2, TRPM4
membrane depolarization during SA node cell action potential487.0×2e-06SCN5A, CACNA1D, HCN4, ANK2
cardiac muscle tissue morphogenesis545.3×3e-06TCAP, TTN, ANKRD1, MYLK2, NKX2-5
ventricular cardiac muscle tissue morphogenesis627.2×3e-06TNNI3, MYBPC3, MYH6, MYH7, MYL3, PKP2
regulation of ventricular cardiac muscle cell membrane depolarization472.5×5e-06SCN5A, CAV3, SCN3B, GPD1L
SA node cell action potential472.5×5e-06SCN5A, HCN4, SCN3B, ANK2
negative regulation of delayed rectifier potassium channel activity472.5×5e-06KCNE1, KCNE2, KCNE3, KCNQ1
cardiac muscle cell development624.2×6e-06TCAP, TTN, CAV3, ACTN2, NKX2-5, MYH6
potassium ion import across plasma membrane716.5×8e-06HCN4, KCNE2, KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1
muscle filament sliding534.0×1e-05TCAP, TNNI3, TTN, MYH6, MYH7
potassium ion export across plasma membrane534.0×1e-05KCNE1, KCNE2, KCNE3, KCNH2, KCNQ1

Therapeutics

Drug target analysis

Approved (phase 4): 17 · Phase ≥3: 17 · Phased (≥1): 23 · Undrugged: 52

Druggability breadth: 83 of 169 evidence-associated genes (49%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
SCN4ACARBAMAZEPINE
SCN5ABEPRIDIL
SLC6A2CETIRIZINE
SYKFEDRATINIB
TOP2AIDARUBICIN
CACNA1CREMIFENTANIL
CACNA1DBEPRIDIL
CACNA1SBEPRIDIL
CACNA2D1PREGABALIN
CACNB2NIMODIPINE
STK32BNERATINIB
CALM1CLOZAPINE
SIRT6NIACINAMIDE
MYLK2FEDRATINIB
HCN4IVABRADINE
CITMOMELOTINIB
HKDC1CHLORHEXIDINE

Top cohort targets by molecule count

SymbolMoleculesMax phase
SLC6A24714
SCN5A1084
CACNA1C854
SYK544
CACNA1D484
CACNA1S484
CIT414
SCN4A244
TOP2A194
MYLK2194

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
CARBAMAZEPINE4SCN4A, SCN5A
PHENYTOIN4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A
LAMOTRIGINE4SCN4A, SCN5A
RILUZOLE4SCN4A, SCN5A, SLC6A2
LIDOCAINE4SCN4A, SCN5A
IMIPRAMINE4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A, SLC6A2
SERTINDOLE4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A, SLC6A2
PIMOZIDE4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A, SLC6A2
NIFEDIPINE4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A
DILTIAZEM4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A
MIBEFRADIL4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A, SLC6A2
HALOPERIDOL4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A, SLC6A2
MEXILETINE4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A
AMITRIPTYLINE4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A, SLC6A2
AMIODARONE4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A, SLC6A2
CHLORPROMAZINE4CACNA1C, CACNA1D, CACNA1S, CALM1, SCN4A, SCN5A
BEPRIDIL4CACNA1C, CACNA1D, CACNA1S, SCN5A, SLC6A2
CANDESARTAN CILEXETIL4SCN5A, SLC6A2
TELMISARTAN4SCN5A
DIBUCAINE4CACNA1C, SCN5A
DROPERIDOL4CACNA1C, CACNA1D, CACNA1S, SCN5A
PONATINIB4SCN5A, SLC6A2
DULOXETINE4CACNA1C, CACNA1D, CACNA1S, SCN5A, SLC6A2
PALONOSETRON4SCN5A
VILANTEROL4SCN5A, SLC6A2
MEXILETINE HYDROCHLORIDE4SCN5A
UNOPROSTONE ISOPROPYL4SCN5A, SLC6A2
LURASIDONE4SCN5A, SLC6A2
LETERMOVIR4SCN5A
FEDRATINIB4CIT, MYLK2, SCN5A, SLC6A2, SYK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 10.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

SymbolAssaysType breakdown
TOP2A1,305Binding:1264, ADMET:22, Functional:13, Toxicity:6
SLC6A2929Binding:885, ADMET:25, Functional:15, Toxicity:3, Unclassified:1
SYK873Binding:863, Functional:10
SCN5A594Binding:380, Functional:98, ADMET:72, Toxicity:43, Unclassified:1
CACNA1C575Binding:319, Functional:211, Toxicity:26, ADMET:19
SIRT6244Binding:240, Functional:4
CACNA1D233Binding:145, Functional:81, Toxicity:5, ADMET:2
CACNA1S228Binding:142, Functional:79, Toxicity:5, ADMET:2
MYLK2196Binding:196
CIT145Binding:145
STK32B118Binding:118
SCN4A95Binding:69, Functional:18, ADMET:7, Toxicity:1
ERAP188Binding:85, Functional:2, ADMET:1
CACNA2D147Binding:45, ADMET:1, Toxicity:1
HCN430Binding:20, ADMET:5, Functional:4, Toxicity:1
CALM123Binding:23
CACNB222Binding:20, ADMET:1, Toxicity:1
UPP118Binding:18
RYR116Binding:13, Functional:3
RYR215Binding:15
SCN1B15Binding:7, ADMET:6, Toxicity:2
TRPM414Binding:13, Functional:1
USP1913Binding:13
MDN19Binding:9
TMPO7Binding:7
HKDC17Functional:6, Binding:1
SNAPC46Binding:6
UBR76Binding:6
WDR266Binding:6
RHEB4Binding:4
SLC2A53Binding:3
TNNI32Binding:2
VCL2Binding:2
NET12Binding:2
SDC11Binding:1
TGFB31Binding:1
TTN1Binding:1
CALM21Binding:1
LRBA1Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
RHEB3.6.5.2small monomeric GTPase
SYK2.7.10.2, 2.7.12.1non-specific protein-tyrosine kinase, dual-specificity kinase
TOP2A5.6.2.2, 5.99.1.3DNA topoisomerase (ATP-hydrolysing), DNA topoisomerase (ATP-hydrolysing)
TTN2.7.11.1non-specific serine/threonine protein kinase
UPP12.4.2.3uridine phosphorylase
YME1L13.4.24.B18
SIRT62.3.1.B41
MYLK22.7.11.18myosin-light-chain kinase
ERAP13.4.11.1, 3.4.11.22leucyl aminopeptidase, aminopeptidase I
HKDC12.7.1.1hexokinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

SymbolChEMBL assays
SCN5A594
SLC6A2929
SYK873
TOP2A1,305
CACNA1C575
CACNA1D233
CACNA1S228
STK32B118
SIRT6244
MYLK2196
CIT145

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 2.

Cohort genes with a CPIC/DPWG dosing guideline

SymbolCPIC guidelines
RYR11
CACNA1S1

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

CompoundMax phaseCohort target (bioactivity)
CARBAMAZEPINE4SCN4A, SCN5A
PHENYTOIN4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A
LAMOTRIGINE4SCN4A, SCN5A
RILUZOLE4SCN4A, SCN5A, SLC6A2
LIDOCAINE4SCN4A, SCN5A
IMIPRAMINE4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A, SLC6A2
SERTINDOLE4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A, SLC6A2
PIMOZIDE4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A, SLC6A2
NIFEDIPINE4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A
DILTIAZEM4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A
MIBEFRADIL4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A, SLC6A2
HALOPERIDOL4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A, SLC6A2
MEXILETINE4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A
AMITRIPTYLINE4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A, SLC6A2
AMIODARONE4CACNA1C, CACNA1D, CACNA1S, SCN4A, SCN5A, SLC6A2
CHLORPROMAZINE4CACNA1C, CACNA1D, CACNA1S, CALM1, SCN4A, SCN5A
BEPRIDIL4CACNA1C, CACNA1D, CACNA1S, SCN5A, SLC6A2
CANDESARTAN CILEXETIL4SCN5A, SLC6A2
TELMISARTAN4SCN5A
DIBUCAINE4CACNA1C, SCN5A
DROPERIDOL4CACNA1C, CACNA1D, CACNA1S, SCN5A
PONATINIB4SCN5A, SLC6A2
DULOXETINE4CACNA1C, CACNA1D, CACNA1S, SCN5A, SLC6A2
PALONOSETRON4SCN5A
VILANTEROL4SCN5A, SLC6A2
MEXILETINE HYDROCHLORIDE4SCN5A
UNOPROSTONE ISOPROPYL4SCN5A, SLC6A2
LURASIDONE4SCN5A, SLC6A2
LETERMOVIR4SCN5A
FEDRATINIB4CIT, MYLK2, SCN5A, SLC6A2, SYK

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)17SCN4A, SCN5A, SLC6A2, SYK, TOP2A, CACNA1C, CACNA1D, CACNA1S, CACNA2D1, CACNB2 (+7 more)
BPhased (≥1) drug, not yet approved6RYR2, SCN1B, SNAPC4, ERAP1, MDN1, WDR26
CDruggable family + PDB, no drug9RHEB, RYR1, TTN, UPP1, USP19, TRPM4, CELSR1, CD276, SCN3B
DDruggable family + AlphaFold only, no drug3SLC2A5, YME1L1, MYPN
EDifficult family or no structure, no drug40RNF207, SDC1, SNTA1, TCAP, TGFB3, TMPO, TNFRSF6B, TNNI3, VCL, VSX1 (+30 more)

Undrugged target profiles

52 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
SNTA10SCN5A
JPH20RYR2
CASQ20RYR2, CACNA1C
SNAPC50SNAPC4
REM10CACNA1C
SCN3B0SCN5A
RNF2070
RHEB4
RYR116
SDC11
SLC2A53
TCAP0
TGFB31
TMPO7
TNFRSF6B0
TNNI32
TTN1
UPP118
USP1913
VCL2
VSX10
YME1L10
ZNF1740
TLNRD10
SHANK30
CALM21
NET12
CRELD10
CAV30
LDB30

Clinical trials & evidence

Clinical trials

Clinical trials: 66.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified52
PHASE16
PHASE44
PHASE23
PHASE1/PHASE21

Top trials by phase / activity

NCTPhaseStatusTitle
NCT02513940PHASE4COMPLETEDInfluence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883PHASE4COMPLETEDReducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100PHASE4UNKNOWNNovel Form of Acquired Long QT Syndrome
NCT04675788PHASE4COMPLETEDNovel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205PHASE2COMPLETEDLong-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709PHASE2UNKNOWNLong QT Syndrome Screening in Newborns
NCT04581408PHASE2COMPLETEDMutation-specific Therapy for the Long QT Syndrome
NCT05906732PHASE1/PHASE2TERMINATEDStudy of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00316459PHASE1COMPLETEDStudy Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003PHASE1COMPLETEDStudy of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532PHASE1COMPLETEDEffect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098PHASE1COMPLETEDPharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829PHASE1COMPLETEDPharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962PHASE1COMPLETEDPhase 1 Study of LQT-1213 in Healthy Adults
NCT02413450Not specifiedENROLLING_BY_INVITATIONDerivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT03775954Not specifiedRECRUITINGFetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise
NCT04189822Not specifiedENROLLING_BY_INVITATIONHearts in Rhythm Organization (HiRO)National Registry and Bio Bank
NCT04336644Not specifiedRECRUITINGContinuous Versus Intermittent cARdiac Electrical moNitorinG
NCT05348564Not specifiedRECRUITINGComparing Direct vs Indirect Methods for Cascade Screening
NCT05521451Not specifiedRECRUITINGClinical Cohort Study - TRUST
NCT06087367Not specifiedRECRUITINGBuilding of a Diagnostic/Prognostic Database for Human ERG Variant Effects
NCT06546137Not specifiedRECRUITINGNational Network for Cardiovascular Genomics: Advancing Cardiovascular Healthcare for Hereditary Diseases in Brazil’s Unified Health System Through a Multicenter Registry
NCT06661278Not specifiedRECRUITINGEvaluation of Exercise Testing and Physical Activity in Children and Adolescents Living With Inherited Arrhythmias
NCT06887387Not specifiedRECRUITINGWearable Devices for Patient Monitoring in Long QT Syndrome
NCT07233421Not specifiedENROLLING_BY_INVITATIONFrequency of Hypoglycemia in Children With Beta-blocker Treated Long QT-syndrome
NCT00005176Not specifiedCOMPLETEDLong QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250Not specifiedCOMPLETEDLinkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367Not specifiedCOMPLETEDEpidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832Not specifiedUNKNOWNMolecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032Not specifiedCOMPLETEDRegistry of Unexplained Cardiac Arrest
NCT00335036Not specifiedTERMINATEDPediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412Not specifiedCOMPLETEDECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254Not specifiedCOMPLETEDThe Long QT Syndrome in Pregnancy
NCT00588965Not specifiedCOMPLETEDEffect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925Not specifiedCOMPLETEDMulticenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564Not specifiedCOMPLETEDFetal and Neonatal Magnetophysiology
NCT02082431Not specifiedCOMPLETEDDetermine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02425189Not specifiedCOMPLETEDThe Canadian National Long QT Syndrome Registry
NCT02439645Not specifiedTERMINATEDA Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658Not specifiedUNKNOWNGenetics of QT Prolongation With Antiarrhythmics

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
IBUTILIDE43
PROGESTERONE43
DOFETILIDE42
TESTOSTERONE42
ADENOSINE41
LUMACAFTOR41
PREDNISONE41
RANOLAZINE41
ELECLAZINE34
PRINABEREL21
CHEMBL474647202
CHEMBL1572001
CHEMBL60629801