VACTERL/vater association

Summary

VACTERL/vater association (MONDO:0008642) is a disease with 35 cohort genes and 1 clinical trial.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 35
• ClinVar variants: 37
• Phenotypes (HPO): 41
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	6.25	Europe	Validated

Signs & symptoms

Clinical features (HPO)

41 HPO clinical features (Orphanet curated; top 41 by frequency):

HPO ID	Term	Frequency
HP:0001561	Polyhydramnios	Very frequent (80-99%)
HP:0001622	Premature birth	Very frequent (80-99%)
HP:0002023	Anal atresia	Very frequent (80-99%)
HP:0002777	Tracheal stenosis	Very frequent (80-99%)
HP:0006703	Aplasia/Hypoplasia of the lungs	Very frequent (80-99%)
HP:0000086	Ectopic kidney	Frequent (30-79%)
HP:0000104	Renal agenesis	Frequent (30-79%)
HP:0000776	Congenital diaphragmatic hernia	Frequent (30-79%)
HP:0001601	Laryngomalacia	Frequent (30-79%)
HP:0001671	Abnormal cardiac septum morphology	Frequent (30-79%)
HP:0002575	Tracheoesophageal fistula	Frequent (30-79%)
HP:0003422	Vertebral segmentation defect	Frequent (30-79%)
HP:0006501	Aplasia/Hypoplasia of the radius	Frequent (30-79%)
HP:0030680	Abnormal cardiovascular system morphology	Frequent (30-79%)
HP:0000003	Multicystic kidney dysplasia	Occasional (5-29%)
HP:0000008	Abnormal morphology of female internal genitalia	Occasional (5-29%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000047	Hypospadias	Occasional (5-29%)
HP:0000048	Bifid scrotum	Occasional (5-29%)
HP:0000062	Ambiguous genitalia	Occasional (5-29%)
HP:0000126	Hydronephrosis	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000239	Large fontanelles	Occasional (5-29%)
HP:0000772	Abnormal rib morphology	Occasional (5-29%)
HP:0000795	Abnormality of the urethra	Occasional (5-29%)
HP:0001048	Cavernous hemangioma	Occasional (5-29%)
HP:0001177	Preaxial hand polydactyly	Occasional (5-29%)
HP:0001195	Single umbilical artery	Occasional (5-29%)
HP:0001511	Intrauterine growth retardation	Occasional (5-29%)
HP:0001539	Omphalocele	Occasional (5-29%)
HP:0001732	Abnormality of the pancreas	Occasional (5-29%)
HP:0002085	Occipital encephalocele	Occasional (5-29%)
HP:0002323	Anencephaly	Occasional (5-29%)
HP:0005107	Abnormal sacrum morphology	Occasional (5-29%)
HP:0005108	Abnormal intervertebral disk morphology	Occasional (5-29%)
HP:0005264	Abnormality of the gallbladder	Occasional (5-29%)
HP:0006101	Finger syndactyly	Occasional (5-29%)
HP:0008736	Hypoplasia of penis	Occasional (5-29%)
HP:0012732	Anorectal anomaly	Occasional (5-29%)
HP:0100335	Non-midline cleft of the upper lip	Occasional (5-29%)
HP:0000358	Posteriorly rotated ears	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	VACTERL/vater association
Mondo ID	MONDO:0008642
OMIM	192350
Orphanet	887
DOID	DOID:14679
ICD-11	1452617987
NCIT	C99105
SNOMED CT	27742002
UMLS	C4225671
MedGen	902479
GARD	0005443
MedDRA	10053665, 10066022
NORD	1818
Is cancer (heuristic)	no

Also known as: VACTERL Association · VACTERL association · VATER association · vertebral abnormalities, anal atresia, Cardiac abnormalities, tracheo-esophageal fistula, renal anomalies, limb defects syndrome

Data availability: 37 ClinVar variants · 1 cell line.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › syndromic disease › VACTERL/vater association

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, long QT syndrome, 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, 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): VACTERL association, X-linked, with or without hydrocephalus

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

37 retrieved; paginated sample, class counts are floors:

16 likely benign, 6 conflicting classifications of pathogenicity, 6 uncertain significance, 5 likely pathogenic, 2 pathogenic, 1 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
393547	GRCh37/hg19 17q12(chr17:34815551-36208392)x1	AATF	Pathogenic	no assertion criteria provided
209076	NM_018062.4(FANCL):c.268del (p.Leu90fs)	FANCL	Pathogenic	criteria provided, single submitter
393545	GRCh37/hg19 16q23.3(chr16:83414018-83518410)x1	CDH13	Likely pathogenic	no assertion criteria provided
393549	GRCh37/hg19 22q11.21(chr22:18915347-21463730)x1	CLDN5	Likely pathogenic	no assertion criteria provided
393534	GRCh37/hg19 5q23.1(chr5:118890915-119082631)x1	FAM170A	Likely pathogenic	no assertion criteria provided
190130	NM_001451.3(FOXF1):c.658G>T (p.Gly220Cys)	FOXF1	Likely pathogenic	criteria provided, single submitter
393538	GRCh37/hg19 10q11.21(chr10:43796180-44037408)x3	FXYD4	Likely pathogenic	no assertion criteria provided
45898	NM_022124.6(CDH23):c.2572G>A (p.Val858Ile)	CDH23	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2848472	NM_001378414.1(HDAC4):c.949G>A (p.Ala317Thr)	HDAC4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2060680	NM_000921.5(PDE3A):c.293C>A (p.Ala98Glu)	LOC124625920	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178395	NM_001384474.1(LOXHD1):c.5023C>T (p.Arg1675Cys)	LOXHD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1462882	NM_000430.4(PAFAH1B1):c.1181A>G (p.Tyr394Cys)	PAFAH1B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3306750	NM_002653.5(PITX1):c.20G>T (p.Gly7Val)	PITX1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2147273	NM_022124.6(CDH23):c.9974G>A (p.Arg3325His)	CDH23	Uncertain significance	criteria provided, multiple submitters, no conflicts
1806723	NM_017780.4(CHD7):c.3158G>A (p.Arg1053His)	CHD7	Uncertain significance	criteria provided, multiple submitters, no conflicts
14877	NM_000523.4(HOXD13):c.164_184del (p.Gly55_Ala61del)	HOXD13	Uncertain significance	no assertion criteria provided
4074875	NM_001145809.2(MYH14):c.1801G>A (p.Asp601Asn)	MYH14	Uncertain significance	criteria provided, single submitter
596711	NM_024408.4(NOTCH2):c.3556T>A (p.Tyr1186Asn)	NOTCH2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2442134	NM_016292.3(TRAP1):c.472G>C (p.Asp158His)	TRAP1	Uncertain significance	criteria provided, single submitter
393546	GRCh37/hg19 17p13.3(chr17:1007540-1254875)x3	ABR	Likely benign	no assertion criteria provided
393535	GRCh37/hg19 7p21.2(chr7:15424383-15534832)x3	AGMO	Likely benign	no assertion criteria provided
393544	GRCh37/hg19 15q25.2-25.3(chr15:84931022-85728834)x1	ALPK3	Likely benign	no assertion criteria provided
393540	GRCh37/hg19 12q23.1(chr12:100367541-100489446)x1	ANKS1B	Likely benign	no assertion criteria provided
1555340	NM_001128840.3(CACNA1D):c.925G>A (p.Val309Ile)	CACNA1D	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
393531	GRCh37/hg19 2q21.1(chr2:132140614-132312325)x3	CCDC74A	Likely benign	no assertion criteria provided
393536	GRCh37/hg19 7q35(chr7:147516080-147803861)x1	CNTNAP2	Likely benign	no assertion criteria provided
393541	GRCh37/hg19 13q14.11(chr13:43505151-43762719)x3	DNAJC15	Likely benign	no assertion criteria provided
393537	GRCh37/hg19 9q22.32(chr9:97290466-97419146)x1	FBP1	Likely benign	no assertion criteria provided
393542	GRCh37/hg19 13q31.3(chr13:93377562-93606814)x1	GPC5	Likely benign	no assertion criteria provided
4074845	NM_001384474.1(LOXHD1):c.2834G>A (p.Gly945Asp)	LOXHD1	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 41 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDH23	Orphanet:231169	Usher syndrome type 1
CDH23	Orphanet:2965	Prolactinoma
CDH23	Orphanet:314777	Familial isolated pituitary adenoma
CDH23	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
CDH23	Orphanet:91347	TSH-secreting pituitary adenoma
CDH23	Orphanet:96253	Cushing disease
CNTNAP2	Orphanet:163681	CNTNAP2-related developmental and epileptic encephalopathy
CACNA1D	Orphanet:324321	Sinoatrial node dysfunction and deafness
CACNA1D	Orphanet:369929	Primary hyperaldosteronism-seizures-neurological abnormalities syndrome
HDAC4	Orphanet:1001	2q37 microdeletion syndrome
NALCN	Orphanet:1146	Distal arthrogryposis type 1
NALCN	Orphanet:1147	Sheldon-Hall syndrome
NALCN	Orphanet:2053	Freeman-Sheldon syndrome
NALCN	Orphanet:562528	Congenital limbs-face contractures-hypotonia-developmental delay syndrome
NALCN	Orphanet:700336	Hypotonia-speech impairment-severe cognitive delay syndrome due to NALCN deficiency
CHD7	Orphanet:138	CHARGE syndrome
CHD7	Orphanet:39041	Omenn syndrome
CHD7	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
CHD7	Orphanet:478	Kallmann syndrome
FANCL	Orphanet:84	Fanconi anemia
MYH14	Orphanet:397744	MYH14-related peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome
MYH14	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
LOXHD1	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
FBP1	Orphanet:348	Fructose-1,6-bisphosphatase deficiency
FOXF1	Orphanet:210122	Congenital alveolar capillary dysplasia
HOXD13	Orphanet:295191	Zygodactyly type 3
HOXD13	Orphanet:295195	Synpolydactyly type 1
HOXD13	Orphanet:887	VACTERL/VATER association
HOXD13	Orphanet:93387	Brachydactyly type E
HOXD13	Orphanet:93406	Syndactyly type 5
HOXD13	Orphanet:93409	Brachydactyly-syndactyly, Zhao type
NOTCH2	Orphanet:261629	Alagille syndrome due to a NOTCH2 point mutation
NOTCH2	Orphanet:955	Hajdu-Cheney syndrome
PAFAH1B1	Orphanet:217385	17p13.3 microduplication syndrome
PAFAH1B1	Orphanet:531	Miller-Dieker syndrome
PAFAH1B1	Orphanet:95232	Lissencephaly due to LIS1 mutation
PAFAH1B1	Orphanet:99796	Subcortical band heterotopia
PITX1	Orphanet:1275	Brachydactyly-elbow wrist dysplasia syndrome
PITX1	Orphanet:293144	Familial clubfoot due to 5q31 microdeletion
PITX1	Orphanet:293150	Familial clubfoot due to PITX1 point mutation
PITX1	Orphanet:498494	Mirror-image polydactyly

Cohort genes → proteins

35 cohort genes, 35 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	35

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HSP90B2P	HGNC:12099	ENSG00000259706	Q58FF3	Putative endoplasmin-like protein	clinvar
CDH23	HGNC:13733	ENSG00000107736	Q9H251	Cadherin-23	clinvar
CNTNAP2	HGNC:13830	ENSG00000174469	Q9UHC6	Contactin-associated protein-like 2	clinvar
CACNA1D	HGNC:1391	ENSG00000157388	Q01668	Voltage-dependent L-type calcium channel subunit alpha-1D	clinvar
HDAC4	HGNC:14063	ENSG00000068024	P56524	Histone deacetylase 4	clinvar
SHANK1	HGNC:15474	ENSG00000161681	Q9Y566	SH3 and multiple ankyrin repeat domains protein 1	clinvar
SMYD3	HGNC:15513	ENSG00000185420	Q9H7B4	Histone-lysine N-methyltransferase SMYD3	clinvar
TRAP1	HGNC:16264	ENSG00000126602	Q12931	Heat shock protein 75 kDa, mitochondrial	clinvar
SORCS1	HGNC:16697	ENSG00000108018	Q8WY21	VPS10 domain-containing receptor SorCS1	clinvar
NREP	HGNC:16834	ENSG00000134986	Q16612	Neuronal regeneration-related protein	clinvar
CDH13	HGNC:1753	ENSG00000140945	P55290	Cadherin-13	clinvar
ALPK3	HGNC:17574	ENSG00000136383	Q96L96	Alpha-protein kinase 3	clinvar
NALCN	HGNC:19082	ENSG00000102452	Q8IZF0	Sodium leak channel NALCN	clinvar
AATF	HGNC:19235	ENSG00000275700	Q9NY61	Protein AATF	clinvar
DNAJC15	HGNC:20325	ENSG00000120675	Q9Y5T4	DnaJ homolog subfamily C member 15	clinvar
CLDN5	HGNC:2047	ENSG00000184113	O00501	Claudin-5	clinvar
CHD7	HGNC:20626	ENSG00000171316	Q9P2D1	ATP-dependent chromatin remodeler CHD7	clinvar
FANCL	HGNC:20748	ENSG00000115392	Q9NW38	E3 ubiquitin-protein ligase FANCL	clinvar
MYH14	HGNC:23212	ENSG00000105357	Q7Z406	Myosin-14	clinvar
PARM1	HGNC:24536	ENSG00000169116	Q6UWI2	Prostate androgen-regulated mucin-like protein 1	clinvar
ANKS1B	HGNC:24600	ENSG00000185046	Q7Z6G8	Ankyrin repeat and sterile alpha motif domain-containing protein 1B	clinvar
CCDC74A	HGNC:25197	ENSG00000163040	Q96AQ1	Coiled-coil domain-containing protein 74A	clinvar
LOXHD1	HGNC:26521	ENSG00000167210	Q8IVV2	Lipoxygenase homology domain-containing protein 1	clinvar
METRNL	HGNC:27584	ENSG00000176845	Q641Q3	Meteorin-like protein	clinvar
FAM170A	HGNC:27963	ENSG00000164334	A1A519	Protein FAM170A	clinvar
AGMO	HGNC:33784	ENSG00000187546	Q6ZNB7	Alkylglycerol monooxygenase	clinvar
FBP1	HGNC:3606	ENSG00000165140	P09467	Fructose-1,6-bisphosphatase 1	clinvar
FOXF1	HGNC:3809	ENSG00000103241	Q12946	Forkhead box protein F1	clinvar
FXYD4	HGNC:4028	ENSG00000150201	P59646	FXYD domain-containing ion transport regulator 4	clinvar
GPC5	HGNC:4453	ENSG00000179399	P78333	Glypican-5	clinvar
HOXD13	HGNC:5136	ENSG00000128714	P35453	Homeobox protein Hox-D13	clinvar
NOTCH2	HGNC:7882	ENSG00000134250	Q04721	Neurogenic locus notch homolog protein 2	clinvar
ABR	HGNC:81	ENSG00000159842	Q12979	Active breakpoint cluster region-related protein	clinvar
PAFAH1B1	HGNC:8574	ENSG00000007168	P43034	Platelet-activating factor acetylhydrolase IB subunit beta	clinvar
PITX1	HGNC:9004	ENSG00000069011	P78337	Pituitary homeobox 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HSP90B2P	Putative endoplasmin-like protein	Putative molecular chaperone.
CDH23	Cadherin-23	Cadherins are calcium-dependent cell adhesion proteins.
CNTNAP2	Contactin-associated protein-like 2	Required for gap junction formation.
CACNA1D	Voltage-dependent L-type calcium channel subunit alpha-1D	Voltage-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…
HDAC4	Histone deacetylase 4	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
SHANK1	SH3 and multiple ankyrin repeat domains protein 1	Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and H…
SMYD3	Histone-lysine N-methyltransferase SMYD3	Histone methyltransferase.
TRAP1	Heat shock protein 75 kDa, mitochondrial	Chaperone that expresses an ATPase activity.
NREP	Neuronal regeneration-related protein	May have roles in neural function.
CDH13	Cadherin-13	Cadherins are calcium-dependent cell adhesion proteins.
ALPK3	Alpha-protein kinase 3	Involved in cardiomyocyte differentiation.
NALCN	Sodium leak channel NALCN	Voltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability.
AATF	Protein AATF	Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit.
DNAJC15	DnaJ homolog subfamily C member 15	Negative regulator of the mitochondrial respiratory chain.
CLDN5	Claudin-5	Plays a major role in tight junction-specific obliteration of the intercellular space.
CHD7	ATP-dependent chromatin remodeler CHD7	ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP.
FANCL	E3 ubiquitin-protein ligase FANCL	Ubiquitin ligase protein that mediates monoubiquitination of FANCD2 in the presence of UBE2T, a key step in the DNA damage pathway.
MYH14	Myosin-14	Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.
PARM1	Prostate androgen-regulated mucin-like protein 1	May regulate TLP1 expression and telomerase activity, thus enabling certain prostatic cells to resist apoptosis.
ANKS1B	Ankyrin repeat and sterile alpha motif domain-containing protein 1B	Isoform 2 may participate in the regulation of nucleoplasmic coilin protein interactions in neuronal and transformed cells.
LOXHD1	Lipoxygenase homology domain-containing protein 1	Involved in hearing.
METRNL	Meteorin-like protein	Hormone induced following exercise or cold exposure that promotes energy expenditure.
FAM170A	Protein FAM170A	Acts as a nuclear transcription factor that positively regulates the expression of heat shock genes.
AGMO	Alkylglycerol monooxygenase	Glyceryl-ether monooxygenase that cleaves the O-alkyl bond of ether lipids.
FBP1	Fructose-1,6-bisphosphatase 1	Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
FOXF1	Forkhead box protein F1	Probable transcription activator for a number of lung-specific genes.
FXYD4	FXYD domain-containing ion transport regulator 4	Associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane.
GPC5	Glypican-5	Cell surface proteoglycan that bears heparan sulfate.
HOXD13	Homeobox protein Hox-D13	Sequence-specific transcription factor that binds gene promoters and activates their transcription.
NOTCH2	Neurogenic locus notch homolog protein 2	Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination.
ABR	Active breakpoint cluster region-related protein	Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins.
PAFAH1B1	Platelet-activating factor acetylhydrolase IB subunit beta	Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participate…
PITX1	Pituitary homeobox 1	Sequence-specific transcription factor that binds gene promoters and activates their transcription.

Protein-family classification

Druggable: 8 · Difficult: 11 · Unknown: 16 · Druggable fraction: 0.23

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.

Family	Genes	Fold	FDR
Ion channel	3	9.6×	0.030
Scaffold/PPI	6	3.0×	0.057
Phosphatase	1	2.4×	0.841
Transcription factor	5	1.2×	0.841
Antibody/Immunoglobulin	1	0.8×	0.915
Other/Unknown	16	0.8×	0.915
Kinase	1	0.8×	0.915
Enzyme (other)	2	0.7×	0.915

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HSP90B2P	Other/Unknown	no		Hsp90_fam, Ribosomal_Su5_D2-typ_SF, HSP90_C
CDH23	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
CNTNAP2	Other/Unknown	no		FA58C, EGF, Laminin_G
CACNA1D	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, LVDCC_a1dsu
HDAC4	Enzyme (other)	yes	3.5.1.98	HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
SHANK1	Scaffold/PPI	no		SH3_domain, PDZ, SAM
SMYD3	Transcription factor	no	2.1.1.354	SET_dom, Znf_MYND, TPR-like_helical_dom_sf
TRAP1	Other/Unknown	no		Hsp90_fam, HATPase_dom, Ribosomal_Su5_D2-typ_SF
SORCS1	Antibody/Immunoglobulin	yes		PKD_dom, VPS10, Ig-like_fold
NREP	Other/Unknown	no		Neuronal_3.1
CDH13	Other/Unknown	no		Cadherin-like_dom, Cadherin_pro_dom, Cadherin-like_sf
ALPK3	Kinase	yes		Ig_sub2, Ig_sub, a-kinase_dom
NALCN	Ion channel	yes		Ion_trans_dom, Volt_channel_dom_sf, NALCN
AATF	Other/Unknown	no		AATF_C, AATF, AATF/Bfr2
DNAJC15	Other/Unknown	no		DnaJ_domain, J_dom_sf
CLDN5	Other/Unknown	no		Claudin5, PMP22/EMP/MP20/Claudin, Claudin
CHD7	Other/Unknown	no		SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
FANCL	Transcription factor	no	2.3.2.27	Znf_RING/FYVE/PHD, UBQ-conjugating_enzyme/RWD, FancL_WD-rpt_cont_dom
MYH14	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
PARM1	Other/Unknown	no		PARM1
ANKS1B	Scaffold/PPI	no		SAM, Ankyrin_rpt, PTB/PI_dom
CCDC74A	Other/Unknown	no		CCDC74_C, CCDC92/74_N, CCDC74A/CCDC74B/CCDC92
LOXHD1	Other/Unknown	no		PLAT/LH2_dom, PLAT/LH2_dom_sf, Inner_ear_hair_cell_LOXHD
METRNL	Other/Unknown	no		Meteorin-like
FAM170A	Other/Unknown	no		Spt46-like
AGMO	Enzyme (other)	yes	1.14.16.5	Fatty_acid_hydroxylase, Sterol_desaturase/TMEM195, AGMP_C
FBP1	Phosphatase	yes	3.1.3.11	FBPase_class-1, Fructose_bisphosphatase_AS, FBPtase
FOXF1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
FXYD4	Ion channel	yes		Ion-transport_regulator_FXYD, FXYD4, FXYD_motif
GPC5	Other/Unknown	no		Glypican, Glypican_CS
HOXD13	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
NOTCH2	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom
ABR	Scaffold/PPI	no		C2_dom, RhoGAP_dom, DH_dom
PAFAH1B1	Scaffold/PPI	no		WD40_rpt, LisH, WD40/YVTN_repeat-like_dom_sf
PITX1	Transcription factor	no		HD, OAR_dom, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	35
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	4
sural nerve	4
gastrocnemius	4
right lung	3
left testis	3
right testis	3
primordial germ cell in gonad	2
corpus callosum	2
superior frontal gyrus	2
gluteal muscle	2
anterior cingulate cortex	2
right frontal lobe	2
hindlimb stylopod muscle	2
right uterine tube	2
cortical plate	2
Brodmann (1909) area 23	2
middle temporal gyrus	2
jejunal mucosa	2
urethra	2
lower esophagus mucosa	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HSP90B2P	108	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, sural nerve
CDH23	161	broad	marker	ventricular zone, left ovary, right ovary
CNTNAP2	127	broad	marker	corpus callosum, superior frontal gyrus, C1 segment of cervical spinal cord
CACNA1D	219	broad	marker	buccal mucosa cell, adrenal tissue, right lung
HDAC4	277	ubiquitous	marker	sural nerve, gluteal muscle, gastrocnemius
SHANK1	183	broad	marker	anterior cingulate cortex, cingulate cortex, right frontal lobe
SMYD3	252	ubiquitous	marker	corpus epididymis, primordial germ cell in gonad, olfactory segment of nasal mucosa
TRAP1	294	ubiquitous	marker	hindlimb stylopod muscle, right uterine tube, gastrocnemius
SORCS1	188	broad	marker	cortical plate, sural nerve, trigeminal ganglion
NREP	292	ubiquitous	marker	cortical plate, paraflocculus, ganglionic eminence
CDH13	152	ubiquitous	marker	descending thoracic aorta, right coronary artery, thoracic aorta
ALPK3	201	broad	yes	gastrocnemius, hindlimb stylopod muscle, gluteal muscle
NALCN	201	ubiquitous	marker	middle temporal gyrus, Brodmann (1909) area 23, corpus callosum
AATF	134	ubiquitous	marker	monocyte, leukocyte, granulocyte
DNAJC15	283	ubiquitous	marker	jejunal mucosa, seminal vesicle, heart right ventricle
CLDN5	268	broad	marker	right lung, upper lobe of lung, upper lobe of left lung
CHD7	269	ubiquitous	marker	secondary oocyte, cerebellar vermis, sural nerve
FANCL	293	ubiquitous	marker	pituitary gland, adenohypophysis, calcaneal tendon
MYH14	227	broad	marker	mucosa of transverse colon, ileal mucosa, gastrocnemius
PARM1	271	broad	marker	urethra, saphenous vein, decidua
ANKS1B	210	broad	marker	Brodmann (1909) area 23, inferior vagus X ganglion, primary visual cortex
CCDC74A	131	ubiquitous	marker	right uterine tube, right testis, left testis
LOXHD1	135	tissue_specific	marker	left testis, right testis, testis
METRNL	134	ubiquitous	marker	lower esophagus mucosa, skin of leg, skin of abdomen
FAM170A	57	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, left testis, right testis
AGMO	118	broad	marker	liver, right lobe of liver, male germ line stem cell (sensu Vertebrata) in testis
FBP1	213	broad	marker	right lobe of liver, endometrium epithelium, jejunal mucosa
FOXF1	202	broad	marker	muscle layer of sigmoid colon, mucosa of stomach, right lung
FXYD4	130	broad	marker	metanephros cortex, renal medulla, adult mammalian kidney
GPC5	181	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, caudate nucleus, putamen

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NOTCH2	5,266
TRAP1	5,216
CHD7	4,819
HDAC4	4,771
SHANK1	3,605
FBP1	3,376
AATF	3,194
PAFAH1B1	3,181
CLDN5	2,645
ANKS1B	2,428

Intra-cohort edges

A	B	Sources
CACNA1D	SHANK1	intact
CDH23	LOXHD1	string_interaction
CDH23	MYH14	string_interaction
FOXF1	HOXD13	biogrid_interaction, intact
METRNL	NOTCH2	intact

Structural data

PDB: 17 · AlphaFold-only: 18 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FBP1	P09467	51
SMYD3	Q9H7B4	34
TRAP1	Q12931	24
PAFAH1B1	P43034	21
HDAC4	P56524	19
FANCL	Q9NW38	8
SHANK1	Q9Y566	7
CDH23	Q9H251	6
CACNA1D	Q01668	6
NALCN	Q8IZF0	5
ANKS1B	Q7Z6G8	4
AATF	Q9NY61	3
CHD7	Q9P2D1	3
MYH14	Q7Z406	2
NOTCH2	Q04721	2
CNTNAP2	Q9UHC6	1
CDH13	P55290	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AGMO	Q6ZNB7	93.90
METRNL	Q641Q3	84.20
LOXHD1	Q8IVV2	84.00
CLDN5	O00501	83.42
HSP90B2P	Q58FF3	82.17
ABR	Q12979	79.10
DNAJC15	Q9Y5T4	78.66
GPC5	P78333	78.66
SORCS1	Q8WY21	77.77
FXYD4	P59646	70.08
NREP	Q16612	67.60
PITX1	P78337	62.81
CCDC74A	Q96AQ1	60.87
FOXF1	Q12946	59.41
HOXD13	P35453	57.18
FAM170A	A1A519	57.06
PARM1	Q6UWI2	52.35
ALPK3	Q96L96	49.15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 135. Enrichment computed across 35 evidence-associated genes (21 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 21 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective LFNG causes SCDO3	1	108.8×	0.110	NOTCH2
RUNX1 regulates expression of components of tight junctions	1	108.8×	0.110	CLDN5
RUNX2 regulates chondrocyte maturation	1	108.8×	0.110	HDAC4
Formation of lateral plate mesoderm	1	108.8×	0.110	FOXF1
Notch-HLH transcription pathway	2	38.8×	0.110	HDAC4, NOTCH2
Sensory processing of sound	2	29.4×	0.110	CDH23, CACNA1D
Cell death signalling via NRAGE, NRIF and NADE	2	20.9×	0.110	AATF, ABR
p75 NTR receptor-mediated signalling	2	17.8×	0.110	AATF, ABR
NRAGE signals death through JNK	2	17.5×	0.110	AATF, ABR
Sensory processing of sound by inner hair cells of the cochlea	2	15.5×	0.110	CDH23, CACNA1D
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	2	13.9×	0.110	HDAC4, NOTCH2
Death Receptor Signaling	2	13.3×	0.110	AATF, ABR
Pre-NOTCH Processing in the Endoplasmic Reticulum	1	90.6×	0.114	NOTCH2
Release of Hh-Np from the secreting cell	1	68.0×	0.141	GPC5
RUNX3 regulates p14-ARF	1	54.4×	0.142	HDAC4
Regulation of CDH11 gene transcription	1	49.4×	0.142	FOXF1
NOTCH2 intracellular domain regulates transcription	1	45.3×	0.142	NOTCH2
Defective EXT2 causes exostoses 2	1	38.8×	0.142	GPC5
Defective EXT1 causes exostoses 1, TRPS2 and CHDS	1	38.8×	0.142	GPC5
Sema4D in semaphorin signaling	1	32.0×	0.142	MYH14
Triglyceride biosynthesis	1	32.0×	0.142	AGMO
Triglyceride metabolism	1	32.0×	0.142	AGMO
Pre-NOTCH Processing in Golgi	1	30.2×	0.142	NOTCH2
RHO GTPases activate CIT	1	28.6×	0.142	MYH14
RHO GTPases Activate ROCKs	1	28.6×	0.142	MYH14
Attachment and Entry	1	28.6×	0.142	GPC5
Defective B4GALT7 causes EDS, progeroid type	1	27.2×	0.142	GPC5
Defective B3GAT3 causes JDSSDHD	1	27.2×	0.142	GPC5
Sema4D induced cell migration and growth-cone collapse	1	27.2×	0.142	MYH14
Defective B3GALT6 causes EDSP2 and SEMDJL1	1	27.2×	0.142	GPC5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 33 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
vocalization behavior	3	80.6×	0.003	CNTNAP2, SHANK1, MYH14
sensory perception of sound	5	15.3×	0.003	CDH23, CACNA1D, CHD7, MYH14, LOXHD1
olfactory behavior	2	113.5×	0.017	SHANK1, CHD7
negative regulation of glycolytic process	2	63.8×	0.043	HDAC4, FBP1
right ventricular compact myocardium morphogenesis	1	510.7×	0.051	CHD7
detection of wounding	1	510.7×	0.051	FOXF1
embryonic ectodermal digestive tract morphogenesis	1	510.7×	0.051	FOXF1
determination of affect	1	510.7×	0.051	SHANK1
right lung morphogenesis	1	510.7×	0.051	FOXF1
branch elongation of an epithelium	1	510.7×	0.051	HOXD13
obsolete membrane lipid metabolic process	1	255.3×	0.051	AGMO
translational attenuation	1	255.3×	0.051	TRAP1
limbic system development	1	255.3×	0.051	CNTNAP2
lateral mesodermal cell differentiation	1	255.3×	0.051	FOXF1
superior temporal gyrus development	1	255.3×	0.051	CNTNAP2
negative regulation of cellular respiration	1	255.3×	0.051	TRAP1
cholangiocyte proliferation	1	255.3×	0.051	NOTCH2
regulation of osteoclast development	1	255.3×	0.051	NOTCH2
branchiomeric skeletal muscle development	1	170.2×	0.051	PITX1
cranial nerve development	1	170.2×	0.051	CHD7
olfactory nerve development	1	170.2×	0.051	CHD7
intrahepatic bile duct development	1	170.2×	0.051	NOTCH2
platelet activating factor metabolic process	1	170.2×	0.051	PAFAH1B1
embryonic hindgut morphogenesis	1	170.2×	0.051	HOXD13
microtubule sliding	1	170.2×	0.051	PAFAH1B1
nuclear membrane disassembly	1	170.2×	0.051	PAFAH1B1
localization within membrane	1	170.2×	0.051	CDH13
low-density lipoprotein particle mediated signaling	1	170.2×	0.051	CDH13
regulation of growth hormone secretion	1	170.2×	0.051	CHD7
trachea development	1	170.2×	0.051	FOXF1

Therapeutics

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 5 · Phased (≥1): 5 · Undrugged: 30

Druggability breadth: 8 of 35 evidence-associated genes (23%) 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.

Symbol	Example approved molecule
CACNA1D	BEPRIDIL
HDAC4	CELECOXIB
MYH14	TUCATINIB
FBP1	ADENOSINE PHOSPHATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CACNA1D	48	4
HDAC4	31	4
TRAP1	9	3
FBP1	5	4
MYH14	1	4
HSP90B2P	0	0
CDH23	0	0
CNTNAP2	0	0
SHANK1	0	0
SMYD3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	CACNA1D
IMIPRAMINE	4	CACNA1D
HALOFANTRINE	4	CACNA1D
DROPERIDOL	4	CACNA1D
SAQUINAVIR	4	CACNA1D
DULOXETINE	4	CACNA1D
DIAZEPAM	4	CACNA1D
SERTINDOLE	4	CACNA1D
QUINIDINE	4	CACNA1D
LAMIVUDINE	4	CACNA1D
PIMOZIDE	4	CACNA1D
PHENYTOIN	4	CACNA1D
TERFENADINE	4	CACNA1D
CISAPRIDE	4	CACNA1D
SOLIFENACIN	4	CACNA1D
NIFEDIPINE	4	CACNA1D
DILTIAZEM	4	CACNA1D
NILOTINIB	4	CACNA1D
ASTEMIZOLE	4	CACNA1D
TERODILINE	4	CACNA1D
CLOZAPINE	4	CACNA1D
MIBEFRADIL	4	CACNA1D
DOFETILIDE	4	CACNA1D
THIORIDAZINE	4	CACNA1D
PAROXETINE	4	CACNA1D
DONEPEZIL	4	CACNA1D
IBUTILIDE	4	CACNA1D
SUNITINIB	4	CACNA1D
HALOPERIDOL	4	CACNA1D
DASATINIB	4	CACNA1D

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

Symbol	Assays	Type breakdown
HDAC4	1,941	Binding:1919, ADMET:13, Functional:6, Toxicity:3
CACNA1D	233	Binding:145, Functional:81, Toxicity:5, ADMET:2
SMYD3	129	Binding:127, Functional:2
FBP1	125	Binding:125
TRAP1	94	Binding:94
ALPK3	10	Binding:10
NOTCH2	2	Binding:2
MYH14	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HDAC4	3.5.1.98	histone deacetylase
SMYD3	2.1.1.354	[histone H3]-lysine4 N-trimethyltransferase
FANCL	2.3.2.27	RING-type E3 ubiquitin transferase
AGMO	1.14.16.5	alkylglycerol monooxygenase
FBP1	3.1.3.11	fructose-bisphosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CACNA1D	233
HDAC4	1,941
SMYD3	129
FBP1	125

Pharmacogenomics

Cohort genes with a PharmGKB record: 35; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

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.

Compound	Max phase	Cohort target (bioactivity)
BEPRIDIL	4	CACNA1D
IMIPRAMINE	4	CACNA1D
HALOFANTRINE	4	CACNA1D
DROPERIDOL	4	CACNA1D
SAQUINAVIR	4	CACNA1D
DULOXETINE	4	CACNA1D
DIAZEPAM	4	CACNA1D
SERTINDOLE	4	CACNA1D
QUINIDINE	4	CACNA1D
LAMIVUDINE	4	CACNA1D
PIMOZIDE	4	CACNA1D
PHENYTOIN	4	CACNA1D
TERFENADINE	4	CACNA1D
CISAPRIDE	4	CACNA1D
SOLIFENACIN	4	CACNA1D
NIFEDIPINE	4	CACNA1D
DILTIAZEM	4	CACNA1D
NILOTINIB	4	CACNA1D
ASTEMIZOLE	4	CACNA1D
TERODILINE	4	CACNA1D
CLOZAPINE	4	CACNA1D
MIBEFRADIL	4	CACNA1D
DOFETILIDE	4	CACNA1D
THIORIDAZINE	4	CACNA1D
PAROXETINE	4	CACNA1D
DONEPEZIL	4	CACNA1D
IBUTILIDE	4	CACNA1D
SUNITINIB	4	CACNA1D
HALOPERIDOL	4	CACNA1D
DASATINIB	4	CACNA1D

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	CACNA1D, HDAC4, MYH14, FBP1
B	Phased (≥1) drug, not yet approved	1	TRAP1
C	Druggable family + PDB, no drug	1	NALCN
D	Druggable family + AlphaFold only, no drug	4	SORCS1, ALPK3, AGMO, FXYD4
E	Difficult family or no structure, no drug	25	HSP90B2P, CDH23, CNTNAP2, SHANK1, SMYD3, NREP, CDH13, AATF, DNAJC15, CLDN5 (+15 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SMYD3	129	—
HSP90B2P	0	—
CDH23	0	—
CNTNAP2	0	—
SHANK1	0	—
SORCS1	0	—
NREP	0	—
CDH13	0	—
ALPK3	10	—
NALCN	0	—
AATF	0	—
DNAJC15	0	—
CLDN5	0	—
CHD7	0	—
FANCL	0	—
PARM1	0	—
ANKS1B	0	—
CCDC74A	0	—
LOXHD1	0	—
METRNL	0	—
FAM170A	0	—
AGMO	0	—
FOXF1	0	—
FXYD4	0	—
GPC5	0	—
HOXD13	0	—
NOTCH2	2	—
ABR	0	—
PAFAH1B1	0	—
PITX1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03799705	Not specified	COMPLETED	Genetic Variants in Nicotinamide Adenine Dinucleotide (NAD) Synthesis Pathway