Meckel syndrome

Summary

Meckel syndrome (MONDO:0018921) is a disease (an umbrella term covering 14 Mondo subtypes) with 38 cohort genes and 1 clinical trial. The dominant Reactome pathway is Anchoring of the basal body to the plasma membrane (11 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Umbrella term: 14 Mondo subtypes
• Cohort genes: 38
• ClinVar variants: 9,763
• Phenotypes (HPO): 45
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

6 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Worldwide	Validated
Prevalence at birth	1-9 / 100 000	4	Worldwide	Validated
Prevalence at birth	1-9 / 100 000	2.6	Europe	Validated
Point prevalence	<1 / 1 000 000		France	Validated
Prevalence at birth	1-9 / 100 000	1.3	France	Validated
Prevalence at birth	1-5 / 10 000	11	Finland	Validated

Signs & symptoms

Clinical features (HPO)

45 HPO clinical features (Orphanet curated; top 45 by frequency):

HPO ID	Term	Frequency
HP:0000003	Multicystic kidney dysplasia	Very frequent (80-99%)
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0001162	Postaxial hand polydactyly	Very frequent (80-99%)
HP:0001830	Postaxial foot polydactyly	Very frequent (80-99%)
HP:0002084	Encephalocele	Very frequent (80-99%)
HP:0002612	Congenital hepatic fibrosis	Very frequent (80-99%)
HP:0000358	Posteriorly rotated ears	Frequent (30-79%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000062	Ambiguous genitalia	Frequent (30-79%)
HP:0000175	Cleft palate	Frequent (30-79%)
HP:0000293	Full cheeks	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000340	Sloping forehead	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000457	Depressed nasal ridge	Frequent (30-79%)
HP:0000482	Microcornea	Frequent (30-79%)
HP:0000518	Cataract	Frequent (30-79%)
HP:0000532	Chorioretinal abnormality	Frequent (30-79%)
HP:0000568	Microphthalmia	Frequent (30-79%)
HP:0000647	Sclerocornea	Frequent (30-79%)
HP:0000648	Optic atrophy	Frequent (30-79%)
HP:0001562	Oligohydramnios	Frequent (30-79%)
HP:0001883	Talipes	Frequent (30-79%)
HP:0006870	Lobar holoprosencephaly	Frequent (30-79%)
HP:0008053	Aplasia/Hypoplasia of the iris	Frequent (30-79%)
HP:0000037	Male pseudohermaphroditism	Occasional (5-29%)
HP:0000068	Urethral atresia	Occasional (5-29%)
HP:0000073	Ureteral duplication	Occasional (5-29%)
HP:0000221	Furrowed tongue	Occasional (5-29%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000528	Anophthalmia	Occasional (5-29%)
HP:0001177	Preaxial hand polydactyly	Occasional (5-29%)
HP:0001305	Dandy-Walker malformation	Occasional (5-29%)
HP:0001696	Situs inversus totalis	Occasional (5-29%)
HP:0001737	Pancreatic cysts	Occasional (5-29%)
HP:0001746	Asplenia	Occasional (5-29%)
HP:0001747	Accessory spleen	Occasional (5-29%)
HP:0002323	Anencephaly	Occasional (5-29%)
HP:0006487	Bowing of the long bones	Occasional (5-29%)
HP:0006706	Cystic liver disease	Occasional (5-29%)
HP:0007370	Aplasia/Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0010295	Aplasia/Hypoplasia of the tongue	Occasional (5-29%)
HP:0010459	True hermaphroditism	Occasional (5-29%)
HP:0030680	Abnormal cardiovascular system morphology	Occasional (5-29%)
HP:0100732	Pancreatic fibrosis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Meckel syndrome
Mondo ID	MONDO:0018921
OMIM	249000
Orphanet	564
DOID	DOID:0050778
ICD-11	695796893
NCIT	C98978
SNOMED CT	29076005
UMLS	C0265215
MedGen	120513
GARD	0003436
Is cancer (heuristic)	no

Also known as: Meckel-Gruber syndrome

Data availability: 9,763 ClinVar variants · 17 GenCC gene-disease records · 4 cell lines.

Disease family

An umbrella term covering 14 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › Meckel 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, 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, 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, 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 (14): Meckel syndrome, type 1, NPHP3-related Meckel-like syndrome, Meckel syndrome, type 2, Meckel syndrome, type 3, Meckel syndrome, type 4, Meckel syndrome, type 5, Meckel syndrome, type 6, Meckel syndrome, type 8, Meckel syndrome, type 10, Meckel syndrome, type 9, Meckel syndrome, type 11, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, meckel syndrome 14, Meckel syndrome 13

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:

245 uncertain significance, 200 likely benign, 69 pathogenic, 44 pathogenic/likely pathogenic, 19 conflicting classifications of pathogenicity, 19 likely pathogenic, 3 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068683	NM_001378615.1(CC2D2A):c.4086del (p.Asp1364fs)	CC2D2A	Pathogenic	criteria provided, single submitter
1069485	NM_001378615.1(CC2D2A):c.3376G>A (p.Glu1126Lys)	CC2D2A	Pathogenic	criteria provided, single submitter
1070038	NM_001378615.1(CC2D2A):c.1297del (p.Gln433fs)	CC2D2A	Pathogenic	criteria provided, single submitter
1071905	NM_001378615.1(CC2D2A):c.4256del (p.Gly1419fs)	CC2D2A	Pathogenic	criteria provided, multiple submitters, no conflicts
1073574	NM_001378615.1(CC2D2A):c.2898_2899dup (p.Ile967fs)	CC2D2A	Pathogenic	criteria provided, single submitter
1074596	NM_001378615.1(CC2D2A):c.1538G>A (p.Trp513Ter)	CC2D2A	Pathogenic	criteria provided, multiple submitters, no conflicts
1074828	NM_001378615.1(CC2D2A):c.2875del (p.Glu959fs)	CC2D2A	Pathogenic	criteria provided, single submitter
1075055	NM_001378615.1(CC2D2A):c.418_419insGAGGGAGGAGCCAAGATGGCCGAATAGGAACAGCTCCGGTCTACAGCTCCCAGCGTGAGCGACGCAGAAGACGGTGATTTCTGCATCTCCATCTGAGGTACCGGGTTCATNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGAAAGAATTGG (p.Glu140delinsGlyGlyArgSerGlnAspGlyArgIleGlyThrAlaProValTyrSerSerGlnArgGluArgArgArgArgArgTer)	CC2D2A	Pathogenic	criteria provided, single submitter
1076226	NC_000004.11:g.(?15480341)(15482457_?)del	CC2D2A	Pathogenic	criteria provided, single submitter
1076327	NM_001378615.1(CC2D2A):c.3320_3321del (p.Phe1107fs)	CC2D2A	Pathogenic	criteria provided, single submitter
1032903	NM_025114.4(CEP290):c.2632del (p.Ile878fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1032904	NM_025114.4(CEP290):c.3934A>T (p.Arg1312Ter)	CEP290	Pathogenic	criteria provided, single submitter
1068566	NM_025114.4(CEP290):c.5783del (p.Lys1928fs)	CEP290	Pathogenic	criteria provided, single submitter
1068669	NM_025114.4(CEP290):c.5348_5351del (p.His1783fs)	CEP290	Pathogenic	criteria provided, single submitter
1068974	NM_025114.4(CEP290):c.1400del (p.Asn467fs)	CEP290	Pathogenic	criteria provided, single submitter
1069520	NM_025114.4(CEP290):c.3488_3494dup (p.Val1166fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069579	NM_025114.4(CEP290):c.5235_5238del (p.Ser1745fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069582	NM_025114.4(CEP290):c.4090G>T (p.Glu1364Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
1069639	NM_025114.4(CEP290):c.1668del (p.Arg557fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069905	NM_025114.4(CEP290):c.843_845del (p.Tyr281_Gln282delinsTer)	CEP290	Pathogenic	criteria provided, single submitter
1070003	NM_025114.4(CEP290):c.6487dup (p.Met2163fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070079	NM_025114.4(CEP290):c.3022G>T (p.Glu1008Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070250	NM_025114.4(CEP290):c.3925C>T (p.Gln1309Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070282	NM_025114.4(CEP290):c.6418_6419insC (p.Val2140fs)	CEP290	Pathogenic	criteria provided, single submitter
1070346	NM_025114.4(CEP290):c.2254C>T (p.Gln752Ter)	CEP290	Pathogenic	criteria provided, single submitter
1070783	NM_025114.4(CEP290):c.6624del (p.Arg2208fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070890	NM_025114.4(CEP290):c.6645del (p.Glu2216fs)	CEP290	Pathogenic	criteria provided, single submitter
1071036	NM_025114.4(CEP290):c.3708dup (p.Arg1237fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071059	NM_025114.4(CEP290):c.3249dup (p.Arg1084fs)	CEP290	Pathogenic	criteria provided, single submitter
1071060	NM_025114.4(CEP290):c.2506_2507del (p.Glu836fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 114 · Orphanet: 67 · 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.

Gene	Classification	Inheritance	Disease	Records
MKS1	Definitive	Autosomal recessive	Meckel syndrome, type 1	11
RPGRIP1L	Definitive	Autosomal recessive	Meckel syndrome, type 5	6
TMEM67	Definitive	Autosomal recessive	Meckel syndrome, type 3	13
B9D1	Strong	Autosomal recessive	Meckel syndrome, type 9	6
B9D2	Strong	Autosomal recessive	Meckel syndrome, type 10	3
TCTN2	Strong	Autosomal recessive	Meckel syndrome, type 8	7
TMEM107	Strong	Autosomal recessive	Meckel syndrome 13	5
TMEM231	Strong	Autosomal recessive	Meckel syndrome, type 11	7
TXNDC15	Strong	Autosomal recessive	meckel syndrome 14	4
CC2D2A	Supportive	Autosomal recessive	Meckel syndrome	7
CEP290	Supportive	Autosomal recessive	Meckel syndrome	10
CSPP1	Supportive	Autosomal recessive	Meckel syndrome	6
TCTN1	Supportive	Autosomal recessive	Meckel syndrome	5
TCTN3	Supportive	Autosomal recessive	Meckel syndrome	9
TMEM216	Supportive	Autosomal recessive	Meckel syndrome	6
TMEM237	Supportive	Autosomal recessive	Meckel syndrome	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TMEM237	Orphanet:220497	Joubert syndrome with renal defect
TMEM237	Orphanet:2318	Joubert syndrome with oculorenal defect
TMEM237	Orphanet:475	Isolated Joubert syndrome
TMEM237	Orphanet:564	Meckel syndrome
TXNDC15	Orphanet:564	Meckel syndrome
B9D1	Orphanet:475	Isolated Joubert syndrome
B9D1	Orphanet:564	Meckel syndrome
TCTN2	Orphanet:475	Isolated Joubert syndrome
TCTN2	Orphanet:564	Meckel syndrome
TCTN1	Orphanet:475	Isolated Joubert syndrome
TCTN1	Orphanet:564	Meckel syndrome
CSPP1	Orphanet:397715	Joubert syndrome with Jeune asphyxiating thoracic dystrophy
CSPP1	Orphanet:475	Isolated Joubert syndrome
CSPP1	Orphanet:564	Meckel syndrome
TMEM67	Orphanet:140976	RHYNS syndrome
TMEM67	Orphanet:1454	Joubert syndrome with hepatic defect
TMEM67	Orphanet:475	Isolated Joubert syndrome
TMEM67	Orphanet:564	Meckel syndrome
TMEM67	Orphanet:84081	Senior-Boichis syndrome
B9D2	Orphanet:475	Isolated Joubert syndrome
B9D2	Orphanet:564	Meckel syndrome
CEP290	Orphanet:110	Bardet-Biedl syndrome
CEP290	Orphanet:2318	Joubert syndrome with oculorenal defect
CEP290	Orphanet:3156	Senior-Loken syndrome
CEP290	Orphanet:564	Meckel syndrome
CEP290	Orphanet:65	Leber congenital amaurosis
RPGRIP1L	Orphanet:1454	Joubert syndrome with hepatic defect
RPGRIP1L	Orphanet:220497	Joubert syndrome with renal defect
RPGRIP1L	Orphanet:564	Meckel syndrome
CC2D2A	Orphanet:1454	Joubert syndrome with hepatic defect
CC2D2A	Orphanet:2318	Joubert syndrome with oculorenal defect
CC2D2A	Orphanet:564	Meckel syndrome
CC2D2A	Orphanet:791	Retinitis pigmentosa
TMEM231	Orphanet:2318	Joubert syndrome with oculorenal defect
TMEM231	Orphanet:2754	Orofaciodigital syndrome type 6
TMEM231	Orphanet:564	Meckel syndrome
MKS1	Orphanet:110	Bardet-Biedl syndrome
MKS1	Orphanet:220493	Joubert syndrome with ocular defect
MKS1	Orphanet:475	Isolated Joubert syndrome
MKS1	Orphanet:564	Meckel syndrome
TCTN3	Orphanet:2753	Orofaciodigital syndrome type 4
TCTN3	Orphanet:2754	Orofaciodigital syndrome type 6
TCTN3	Orphanet:475	Isolated Joubert syndrome
TCTN3	Orphanet:564	Meckel syndrome
TMEM216	Orphanet:2318	Joubert syndrome with oculorenal defect
TMEM216	Orphanet:2754	Orofaciodigital syndrome type 6
TMEM216	Orphanet:564	Meckel syndrome
TMEM216	Orphanet:791	Retinitis pigmentosa
TMEM107	Orphanet:564	Meckel syndrome
ATP6V0A2	Orphanet:2834	Wrinkly skin syndrome

Cohort genes → proteins

38 cohort genes, 36 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	38

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TMEM237	HGNC:14432	ENSG00000155755	Q96Q45	Transmembrane protein 237	gencc,clinvar
TXNDC15	HGNC:20652	ENSG00000113621	Q96J42	Thioredoxin domain-containing protein 15	gencc,clinvar
B9D1	HGNC:24123	ENSG00000108641	Q9UPM9	B9 domain-containing protein 1	gencc,clinvar
TCTN2	HGNC:25774	ENSG00000168778	Q96GX1	Tectonic-2	gencc,clinvar
TCTN1	HGNC:26113	ENSG00000204852	Q2MV58	Tectonic-1	gencc,clinvar
CSPP1	HGNC:26193	ENSG00000104218	Q1MSJ5	Centrosome and spindle pole-associated protein 1	gencc,clinvar
TMEM67	HGNC:28396	ENSG00000164953	Q5HYA8	Meckelin	gencc,clinvar
B9D2	HGNC:28636	ENSG00000123810	Q9BPU9	B9 domain-containing protein 2	gencc,clinvar
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	gencc,clinvar
RPGRIP1L	HGNC:29168	ENSG00000103494	Q68CZ1	Protein fantom	gencc,clinvar
CC2D2A	HGNC:29253	ENSG00000048342	Q9P2K1	Coiled-coil and C2 domain-containing protein 2A	gencc,clinvar
TMEM231	HGNC:37234	ENSG00000205084	Q9H6L2	Transmembrane protein 231	gencc,clinvar
MKS1	HGNC:7121	ENSG00000011143	Q9NXB0	Tectonic-like complex member MKS1	gencc,clinvar
TCTN3	HGNC:24519	ENSG00000119977	Q6NUS6	Tectonic-3	gencc
TMEM216	HGNC:25018	ENSG00000187049	Q9P0N5	Transmembrane protein 216	gencc
TMEM107	HGNC:28128	ENSG00000179029	Q6UX40	Transmembrane protein 107	gencc
BST1	HGNC:1118	ENSG00000109743	Q10588	ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2	clinvar
ATP6V0A2	HGNC:18481	ENSG00000185344	Q9Y487	V-type proton ATPase 116 kDa subunit a 2	clinvar
TTC6	HGNC:19739	ENSG00000139865	Q86TZ1	Tetratricopeptide repeat protein 6	clinvar
EVC2	HGNC:19747	ENSG00000173040	Q86UK5	Limbin	clinvar
KIAA0586	HGNC:19960	ENSG00000100578	Q9BVV6	Protein TALPID3	clinvar
GDPD1	HGNC:20883	ENSG00000153982	Q8N9F7	Lysophospholipase D GDPD1	clinvar
PLPP6	HGNC:23682	ENSG00000205808	Q8IY26	Polyisoprenoid diphosphate/phosphate phosphohydrolase PLPP6	clinvar
FTO	HGNC:24678	ENSG00000140718	Q9C0B1	Alpha-ketoglutarate-dependent dioxygenase FTO	clinvar
RLIG1	HGNC:25322	ENSG00000133641	Q8N999	RNA ligase 1	clinvar
PGAP1	HGNC:25712	ENSG00000197121	Q75T13	GPI inositol-deacylase	clinvar
TMEM17	HGNC:26623	ENSG00000186889	Q86X19	Transmembrane protein 17	clinvar
TMEM138	HGNC:26944	ENSG00000149483	Q9NPI0	Transmembrane protein 138	clinvar
CEP295	HGNC:29366	ENSG00000166004	Q9C0D2	Centrosomal protein of 295 kDa	clinvar
EXOC3L2	HGNC:30162	ENSG00000283632	Q2M3D2	Exocyst complex component 3-like protein 2	clinvar
EXOC4	HGNC:30389	ENSG00000131558	Q96A65	Exocyst complex component 4	clinvar
CCDC172	HGNC:30524	ENSG00000182645	P0C7W6	Coiled-coil domain-containing protein 172	clinvar
EIF2B1	HGNC:3257	ENSG00000111361	Q14232	Translation initiation factor eIF2B subunit alpha	clinvar
SNORD118	HGNC:32952	ENSG00000200463		small nucleolar RNA, C/D box 118	clinvar
CIMIP2B	HGNC:34242	ENSG00000215187	A8MTA8	Ciliary microtubule inner protein 2B	clinvar
EVPLL	HGNC:35236	ENSG00000214860	A8MZ36	Envoplakin-like protein	clinvar
NPHP3-ACAD11	HGNC:48351	ENSG00000274810		NPHP3-ACAD11 readthrough (NMD candidate)	clinvar
PDP1	HGNC:9279	ENSG00000164951	Q9P0J1	[Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 1, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TMEM237	Transmembrane protein 237	Component of the transition zone in primary cilia.
TXNDC15	Thioredoxin domain-containing protein 15	Acts as a positive regulator of ciliary hedgehog signaling.
B9D1	B9 domain-containing protein 1	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
TCTN2	Tectonic-2	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
TCTN1	Tectonic-1	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
CSPP1	Centrosome and spindle pole-associated protein 1	May play a role in cell-cycle-dependent microtubule organization.
TMEM67	Meckelin	Required for ciliary structure and function.
B9D2	B9 domain-containing protein 2	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
CEP290	Centrosomal protein of 290 kDa	Involved in early and late steps in cilia formation.
RPGRIP1L	Protein fantom	Negatively regulates signaling through the G-protein coupled thromboxane A2 receptor (TBXA2R).
CC2D2A	Coiled-coil and C2 domain-containing protein 2A	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
TMEM231	Transmembrane protein 231	Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
MKS1	Tectonic-like complex member MKS1	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
TCTN3	Tectonic-3	Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition.
TMEM216	Transmembrane protein 216	Essential for primary ciliogenesis and embryonic development, facilitating the activation of Hedgehog (Hh) signaling pathway.
TMEM107	Transmembrane protein 107	Plays a role in cilia formation and embryonic patterning.
BST1	ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2	Catalyzes both the synthesis of cyclic ADP-beta-D-ribose (cADPR) from NAD(+), and its hydrolysis to ADP-D-ribose (ADPR).
ATP6V0A2	V-type proton ATPase 116 kDa subunit a 2	Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.
EVC2	Limbin	Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling.
KIAA0586	Protein TALPID3	Required for ciliogenesis and sonic hedgehog/SHH signaling.
GDPD1	Lysophospholipase D GDPD1	Hydrolyzes lysoglycerophospholipids to produce lysophosphatidic acid (LPA) and the corresponding amines.
PLPP6	Polyisoprenoid diphosphate/phosphate phosphohydrolase PLPP6	Magnesium-independent polyisoprenoid diphosphatase that catalyzes the sequential dephosphorylation of presqualene, farnesyl, geranyl and geranylgeranyl diphosphates.
FTO	Alpha-ketoglutarate-dependent dioxygenase FTO	RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis.
RLIG1	RNA ligase 1	Functions as an RNA ligase, in vitro.
PGAP1	GPI inositol-deacylase	GPI inositol-deacylase that catalyzes the remove of the acyl chain linked to the 2-OH position of inositol ring from the GPI-anchored protein (GPI-AP) in the endoplasmic reticulum.
TMEM17	Transmembrane protein 17	Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
TMEM138	Transmembrane protein 138	Required for ciliogenesis.
CEP295	Centrosomal protein of 295 kDa	Centriole-enriched microtubule-binding protein involved in centriole biogenesis.
EXOC4	Exocyst complex component 4	Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
EIF2B1	Translation initiation factor eIF2B subunit alpha	Acts as a component of the translation initiation factor 2B (eIF2B) complex, which catalyzes the exchange of GDP for GTP on eukaryotic initiation factor 2 (eIF2) gamma subunit.
CIMIP2B	Ciliary microtubule inner protein 2B	Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.
PDP1	[Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 1, mitochondrial	Mitochondrial enzyme that catalyzes the dephosphorylation and concomitant reactivation of the alpha subunit of the E1 component of the pyruvate dehydrogenase complex (PDC), thereby stimulating the conversion of pyruvate into acetyl-CoA.

Protein-family classification

Druggable: 5 · Difficult: 0 · Unknown: 33 · Druggable fraction: 0.13

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
Other/Unknown	33	1.6×	2e-04
Phosphatase	1	2.2×	0.651
Protease	1	1.0×	0.651
Enzyme (other)	3	0.9×	0.651

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TMEM237	Other/Unknown	no		TMEM237
TXNDC15	Other/Unknown	no		Thioredoxin_domain, Thioredoxin-like_sf, TXNDC15
B9D1	Other/Unknown	no		C2_B9-type_dom
TCTN2	Other/Unknown	no		TCTN1-3_dom, TCTN1-3, TCTN1-3_N
TCTN1	Other/Unknown	no		TCTN1-3_dom, TCTN1-3, TCTN1-3_N
CSPP1	Other/Unknown	no		CSPP1, CSPP1_C
TMEM67	Other/Unknown	no		Growth_fac_rcpt_cys_sf, Meckelin
B9D2	Other/Unknown	no		C2_B9-type_dom
CEP290	Other/Unknown	no		Cep290, Cep209_CC5
RPGRIP1L	Other/Unknown	no		C2_dom, C2-C2_1, RPGRIP1_fam
CC2D2A	Protease	yes		C2_dom, CC2D2AN-C2, C2_domain_sf
TMEM231	Other/Unknown	no		TMEM231
MKS1	Other/Unknown	no		C2_B9-type_dom
TCTN3	Other/Unknown	no		TCTN1-3_dom, TCTN1-3, TCTN1-3_N
TMEM216	Other/Unknown	no		Uncharacterised_TM-17
TMEM107	Other/Unknown	no		TMEM107
BST1	Other/Unknown	no		ADP-ribosyl_cyclase
ATP6V0A2	Enzyme (other)	yes	7.1.2.1	V-ATPase_116kDa_su, V-type_ATPase_116kDa_su_euka
TTC6	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, Ycf3
EVC2	Other/Unknown	no		Limbin, Limbin/EVC
KIAA0586	Other/Unknown	no		TALPID3
GDPD1	Enzyme (other)	yes	3.1.4.46	PLC-like_Pdiesterase_TIM-brl, GP_PDE_dom, GDPD-Related
PLPP6	Other/Unknown	no		PAP2/HPO, PAP2/HPO_sf
FTO	Enzyme (other)	yes	1.14.11.53	FTO_C, FTO_cat_dom, FTO
RLIG1	Other/Unknown	no		RLIG1
PGAP1	Other/Unknown	no		PGAP1-ab_dom-like, AB_hydrolase_fold, PGAP1/BST1
TMEM17	Other/Unknown	no		Uncharacterised_TM-17
TMEM138	Other/Unknown	no		TM_138
CEP295	Other/Unknown	no		ALMS_motif
EXOC3L2	Other/Unknown	no		EXOC3/Sec6, EXOC3/Sec6_C
EXOC4	Other/Unknown	no		Sec8_exocyst_N, Sec8/EXOC4, Sec8_M
CCDC172	Other/Unknown	no		CCDC172
EIF2B1	Other/Unknown	no		IF-2B-related, NagB/RpiA_transferase-like, elF-2B_alpha_N
SNORD118	Other/Unknown	no
CIMIP2B	Other/Unknown	no		CMI2A-C-like_dom
EVPLL	Other/Unknown	no		Plakin, Spectrin_PEPL/EVPL
NPHP3-ACAD11	Other/Unknown	no
PDP1	Phosphatase	yes	3.1.3.43	PP2C_BS, PPM-type_phosphatase-like_dom, PP2C

Expression context

Cohort genes with no expression data: 0.

34 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)	38
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	9
bronchial epithelial cell	7
calcaneal tendon	6
buccal mucosa cell	6
primordial germ cell in gonad	6
male germ line stem cell (sensu Vertebrata) in testis	5
oocyte	5
olfactory segment of nasal mucosa	4
secondary oocyte	4
stromal cell of endometrium	3
adenohypophysis	3
sperm	3
bronchus	3
endothelial cell	3
adrenal tissue	2
ventricular zone	2
left testis	2
monocyte	2
sural nerve	2
right testis	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TMEM237	250	ubiquitous	marker	calcaneal tendon, adrenal tissue, ventricular zone
TXNDC15	278	ubiquitous	marker	calcaneal tendon, stromal cell of endometrium, colonic epithelium
B9D1	224	ubiquitous	marker	right uterine tube, adenohypophysis, left testis
TCTN2	218	ubiquitous	marker	buccal mucosa cell, tendon of biceps brachii, olfactory bulb
TCTN1	230	ubiquitous	marker	right uterine tube, adenohypophysis, olfactory segment of nasal mucosa
CSPP1	275	ubiquitous	marker	bronchial epithelial cell, sperm, right uterine tube
TMEM67	203	ubiquitous	marker	buccal mucosa cell, right uterine tube, calcaneal tendon
B9D2	138	ubiquitous	marker	right uterine tube, blood, olfactory segment of nasal mucosa
CEP290	278	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone
RPGRIP1L	207	ubiquitous	marker	bronchial epithelial cell, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
CC2D2A	247	ubiquitous	marker	right uterine tube, bronchial epithelial cell, bronchus
TMEM231	257	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
MKS1	182	ubiquitous	marker	right uterine tube, olfactory segment of nasal mucosa, left ovary
TCTN3	267	ubiquitous	marker	corpus epididymis, decidua, stromal cell of endometrium
TMEM216	239	ubiquitous	marker	primordial germ cell in gonad, adenohypophysis, pituitary gland
TMEM107	240	ubiquitous	marker	bronchial epithelial cell, bronchus, right uterine tube
BST1	185	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
ATP6V0A2	239	ubiquitous	marker	skin of leg, sural nerve, stromal cell of endometrium
TTC6	176	broad	marker	buccal mucosa cell, olfactory segment of nasal mucosa, sperm
EVC2	182	ubiquitous	marker	pancreatic ductal cell, calcaneal tendon, primordial germ cell in gonad
KIAA0586	247	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, right testis, left testis
GDPD1	217	ubiquitous	marker	Brodmann (1909) area 23, endothelial cell, Brodmann (1909) area 46
PLPP6	227	ubiquitous	marker	secondary oocyte, oocyte, ileal mucosa
FTO	294	ubiquitous	marker	cortical plate, bronchial epithelial cell, Brodmann (1909) area 10
RLIG1	288	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, oocyte
PGAP1	271	ubiquitous	marker	endothelial cell, ganglionic eminence, upper leg skin
TMEM17	217	broad	yes	buccal mucosa cell, primordial germ cell in gonad, bronchial epithelial cell
TMEM138	245	ubiquitous	marker	right adrenal gland, right adrenal gland cortex, left adrenal gland
CEP295	250	ubiquitous	marker	oocyte, secondary oocyte, sperm
EXOC3L2	195	broad	marker	oocyte, secondary oocyte, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 128.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EXOC4	2,865
CEP290	2,778
EIF2B1	2,548
FTO	2,496
CSPP1	2,300
TMEM237	2,169
ATP6V0A2	2,076
RPGRIP1L	2,027
PDP1	1,952
KIAA0586	1,405

Intra-cohort edges

A	B	Sources
B9D1	B9D2	biogrid_interaction, intact, string_interaction
B9D1	CC2D2A	biogrid_interaction, intact, string_interaction
B9D1	CEP290	string_interaction
B9D1	MKS1	biogrid_interaction, intact, string_interaction
B9D1	RPGRIP1L	string_interaction
B9D1	TCTN1	intact, string_interaction
B9D1	TCTN2	intact, string_interaction
B9D1	TCTN3	string_interaction
B9D1	TMEM107	string_interaction
B9D1	TMEM138	string_interaction
B9D1	TMEM17	intact, string_interaction
B9D1	TMEM216	string_interaction
B9D1	TMEM231	biogrid_interaction, intact, string_interaction
B9D1	TMEM237	string_interaction
B9D1	TMEM67	string_interaction
B9D2	CC2D2A	biogrid_interaction, intact, string_interaction
B9D2	CEP290	string_interaction
B9D2	MKS1	biogrid_interaction, intact
B9D2	RPGRIP1L	string_interaction
B9D2	TCTN1	intact, string_interaction
B9D2	TCTN2	string_interaction
B9D2	TCTN3	intact, string_interaction
B9D2	TMEM107	string_interaction
B9D2	TMEM17	string_interaction
B9D2	TMEM216	string_interaction
B9D2	TMEM231	biogrid_interaction, intact, string_interaction
B9D2	TMEM237	string_interaction
B9D2	TMEM67	string_interaction
CC2D2A	CEP290	string_interaction
CC2D2A	CSPP1	string_interaction
CC2D2A	MKS1	biogrid_interaction, intact, string_interaction
CC2D2A	RPGRIP1L	string_interaction
CC2D2A	TCTN1	intact, string_interaction
CC2D2A	TCTN2	intact, string_interaction
CC2D2A	TCTN3	biogrid_interaction, intact, string_interaction
CC2D2A	TMEM107	string_interaction
CC2D2A	TMEM138	string_interaction
CC2D2A	TMEM17	string_interaction
CC2D2A	TMEM216	string_interaction
CC2D2A	TMEM231	intact, string_interaction
CC2D2A	TMEM237	string_interaction
CC2D2A	TMEM67	string_interaction
CCDC172	CEP295	string_interaction
CCDC172	CIMIP2B	string_interaction
CCDC172	TMEM17	string_interaction
CEP290	CSPP1	intact, string_interaction
CEP290	KIAA0586	intact, string_interaction
CEP290	MKS1	string_interaction
CEP290	RPGRIP1L	string_interaction
CEP290	TCTN1	string_interaction

Structural data

PDB: 7 · AlphaFold-only: 29 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FTO	Q9C0B1	28
EIF2B1	Q14232	27
BST1	Q10588	6
CIMIP2B	A8MTA8	2
TMEM67	Q5HYA8	1
RPGRIP1L	Q68CZ1	1
EXOC4	Q96A65	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GDPD1	Q8N9F7	96.12
TMEM107	Q6UX40	94.21
RLIG1	Q8N999	92.03
TTC6	Q86TZ1	91.96
B9D2	Q9BPU9	89.79
TMEM216	Q9P0N5	89.18
PGAP1	Q75T13	89.15
TMEM231	Q9H6L2	88.65
CCDC172	P0C7W6	88.63
TMEM138	Q9NPI0	86.42
TMEM17	Q86X19	86.20
PDP1	Q9P0J1	83.41
B9D1	Q9UPM9	83.05
ATP6V0A2	Q9Y487	81.94
TCTN1	Q2MV58	78.10
TCTN2	Q96GX1	74.71
EXOC3L2	Q2M3D2	74.26
MKS1	Q9NXB0	74.05
PLPP6	Q8IY26	73.75
EVC2	Q86UK5	73.33
TCTN3	Q6NUS6	71.49
CC2D2A	Q9P2K1	69.46
EVPLL	A8MZ36	69.26
TXNDC15	Q96J42	64.90
TMEM237	Q96Q45	63.79
CEP290	O15078	60.90
CSPP1	Q1MSJ5	57.34
KIAA0586	Q9BVV6	47.61
CEP295	Q9C0D2	44.76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 57. Enrichment computed across 38 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
Anchoring of the basal body to the plasma membrane	11	59.2×	3e-16	B9D1, TCTN2, TCTN1, TMEM67, B9D2, CEP290, RPGRIP1L, CC2D2A (+3 more)
Cilium Assembly	9	46.6×	3e-12	B9D1, TCTN2, TCTN1, TMEM67, B9D2, CEP290, CC2D2A, MKS1 (+1 more)
Organelle biogenesis and maintenance	9	28.3×	2e-10	B9D1, TCTN2, TCTN1, TMEM67, B9D2, CEP290, CC2D2A, MKS1 (+1 more)
Signaling by Hedgehog	2	17.5×	0.069	MKS1, EVC2
Hedgehog ‘off’ state	2	17.0×	0.069	RPGRIP1L, MKS1
Glycerophospholipid catabolism	1	77.7×	0.104	GDPD1
Reversal of alkylation damage by DNA dioxygenases	1	77.7×	0.104	FTO
Attachment of GPI anchor to uPAR	1	60.4×	0.104	PGAP1
Recycling of eIF2:GDP	1	60.4×	0.104	EIF2B1
Lanosterol biosynthesis	1	36.2×	0.150	PLPP6
Regulation of pyruvate dehydrogenase (PDH) complex	1	34.0×	0.150	PDP1
Activation of SMO	1	30.2×	0.151	EVC2
VxPx cargo-targeting to cilium	1	24.7×	0.151	EXOC4
Mitotic Prometaphase	2	6.6×	0.151	B9D2, CEP290
M Phase	2	6.3×	0.151	B9D2, CEP290
Insulin processing	1	21.8×	0.160	EXOC4
Nicotinate metabolism	1	18.8×	0.167	BST1
Insulin receptor recycling	1	18.1×	0.167	ATP6V0A2
Transferrin endocytosis and recycling	1	17.5×	0.167	ATP6V0A2
ROS and RNS production in phagocytes	1	16.0×	0.173	ATP6V0A2
Cell Cycle, Mitotic	2	4.6×	0.189	B9D2, CEP290
Centrosome maturation	1	12.1×	0.206	CEP290
Amplification of signal from the kinetochores	1	9.4×	0.230	B9D2
Metabolism of water-soluble vitamins and cofactors	1	8.6×	0.230	BST1
Post-translational modification: synthesis of GPI-anchored proteins	1	8.0×	0.230	BST1
Loss of Nlp from mitotic centrosomes	1	7.5×	0.230	CEP290
Loss of proteins required for interphase microtubule organization from the centrosome	1	7.5×	0.230	CEP290
Hedgehog ‘on’ state	1	7.5×	0.230	EVC2
Mitotic Spindle Checkpoint	1	7.5×	0.230	B9D2
Translocation of SLC2A4 (GLUT4) to the plasma membrane	1	7.3×	0.230	EXOC4

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
cilium assembly	17	37.9×	1e-21	TMEM237, TXNDC15, B9D1, TCTN2, TCTN1, TMEM67, B9D2, CEP290 (+9 more)
smoothened signaling pathway	8	43.9×	6e-10	B9D1, TCTN2, CC2D2A, TMEM231, EVC2, KIAA0586, TCTN3, TMEM17
non-motile cilium assembly	7	61.6×	8e-10	CEP290, RPGRIP1L, CC2D2A, MKS1, TMEM216, TMEM17, TMEM107
protein localization to ciliary transition zone	4	291.8×	2e-08	TCTN2, TCTN1, CC2D2A, TMEM107
camera-type eye development	4	43.5×	6e-05	B9D1, CEP290, CC2D2A, TMEM231
embryonic digit morphogenesis	4	36.5×	1e-04	B9D1, TMEM231, MKS1, TMEM107
RNA repair	2	340.4×	2e-04	FTO, RLIG1
regulation of smoothened signaling pathway	3	56.7×	4e-04	TCTN1, RPGRIP1L, MKS1
neural tube patterning	2	170.2×	9e-04	RPGRIP1L, TMEM107
regulation of establishment of protein localization	2	145.9×	0.001	CEP290, KIAA0586
neuroepithelial cell differentiation	2	92.8×	0.003	B9D1, TMEM231
determination of left/right symmetry	3	23.2×	0.004	RPGRIP1L, CC2D2A, MKS1
vasculature development	2	68.1×	0.004	B9D1, TMEM231
dorsal/ventral neural tube patterning	2	48.6×	0.008	TCTN1, MKS1
embryonic brain development	2	48.6×	0.008	CC2D2A, MKS1
in utero embryonic development	4	8.7×	0.010	B9D1, TCTN1, RPGRIP1L, TMEM231
motile cilium assembly	2	35.2×	0.013	CC2D2A, MKS1
regulation of cellular extravasation	1	510.7×	0.013	BST1
smoothened signaling pathway involved in regulation of secondary heart field cardioblast proliferation	1	510.7×	0.013	MKS1
central nervous system interneuron axonogenesis	1	510.7×	0.013	TCTN1
regulation of white fat cell proliferation	1	510.7×	0.013	FTO
kidney development	3	12.8×	0.013	CEP290, RPGRIP1L, CC2D2A
positive regulation of smoothened signaling pathway	2	25.5×	0.018	TXNDC15, TMEM216
geranyl diphosphate metabolic process	1	255.3×	0.020	PLPP6
farnesyl diphosphate catabolic process	1	255.3×	0.020	PLPP6
regulation of superoxide metabolic process	1	255.3×	0.020	BST1
obsolete ciliary basal body-plasma membrane docking	1	255.3×	0.020	CEP290
positive regulation of pyruvate decarboxylation to acetyl-CoA	1	255.3×	0.020	PDP1
geranylgeranyl diphosphate catabolic process	1	255.3×	0.020	PLPP6
detection of nodal flow	1	170.2×	0.023	TMEM107

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 37

Druggability breadth: 5 of 38 evidence-associated genes (13%) 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
FTO	FLUORESCEIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FTO	18	4
TMEM237	0	0
TXNDC15	0	0
B9D1	0	0
TCTN2	0	0
TCTN1	0	0
CSPP1	0	0
TMEM67	0	0
B9D2	0	0
CEP290	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FLUORESCEIN	4	FTO
DEMECLOCYCLINE	4	FTO
ROXADUSTAT	4	FTO
MECLOFENAMIC ACID	4	FTO
AMILORIDE	4	FTO
TACRINE	4	FTO
ENTACAPONE	4	FTO
NAFAMOSTAT MESYLATE	3	FTO
DIACEREIN	3	FTO
AMONAFIDE	3	FTO
QUERCETIN	3	FTO
METIZOLINE	2	FTO
LUTEOLIN	2	FTO
FENOBAM ANHYDROUS	2	FTO
FISETIN	2	FTO
MITONAFIDE	2	FTO
BAICALEIN	2	FTO
KAEMPFEROL	1	FTO

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
FTO	153	Binding:153
BST1	3	Binding:3
CSPP1	1	Binding:1
EXOC4	1	Binding:1
EIF2B1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATP6V0A2	7.1.2.1	P-type H+-exporting transporter
GDPD1	3.1.4.46	glycerophosphodiester phosphodiesterase
FTO	1.14.11.53	mRNA N6-methyladenine demethylase
PDP1	3.1.3.43	[pyruvate dehydrogenase (acetyl-transferring)]-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
FTO	153

Pharmacogenomics

Cohort genes with a PharmGKB record: 37; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

18 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)
FLUORESCEIN	4	FTO
DEMECLOCYCLINE	4	FTO
ROXADUSTAT	4	FTO
MECLOFENAMIC ACID	4	FTO
AMILORIDE	4	FTO
TACRINE	4	FTO
ENTACAPONE	4	FTO
NAFAMOSTAT MESYLATE	3	FTO
DIACEREIN	3	FTO
AMONAFIDE	3	FTO
QUERCETIN	3	FTO
METIZOLINE	2	FTO
LUTEOLIN	2	FTO
FENOBAM ANHYDROUS	2	FTO
FISETIN	2	FTO
MITONAFIDE	2	FTO
BAICALEIN	2	FTO
KAEMPFEROL	1	FTO

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	FTO
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	4	CC2D2A, ATP6V0A2, GDPD1, PDP1
E	Difficult family or no structure, no drug	33	TMEM237, TXNDC15, B9D1, TCTN2, TCTN1, CSPP1, TMEM67, B9D2, CEP290, RPGRIP1L (+23 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TMEM237	0	—
TXNDC15	0	—
B9D1	0	—
TCTN2	0	—
TCTN1	0	—
CSPP1	1	—
TMEM67	0	—
B9D2	0	—
CEP290	0	—
RPGRIP1L	0	—
CC2D2A	0	—
TMEM231	0	—
MKS1	0	—
TCTN3	0	—
TMEM216	0	—
TMEM107	0	—
BST1	3	—
ATP6V0A2	0	—
TTC6	0	—
EVC2	0	—
KIAA0586	0	—
GDPD1	0	—
PLPP6	0	—
RLIG1	0	—
PGAP1	0	—
TMEM17	0	—
TMEM138	0	—
CEP295	0	—
EXOC3L2	0	—
EXOC4	1	—

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
NCT01401998	Not specified	RECRUITING	ARPKD Database Study