Craniofacial microsomia

Summary

Craniofacial microsomia (MONDO:0015397) is a disease with 54 cohort genes (14 GWAS associations across 2 studies) and 10 clinical trials.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 54
• GWAS associations: 14
• ClinVar variants: 12
• Phenotypes (HPO): 29
• Clinical trials: 10

Clinical features

Epidemiology

Prevalence records

5 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Worldwide	Validated
Prevalence at birth	1-9 / 100 000		Worldwide	Validated
Point prevalence	1-9 / 100 000	4	Japan	Validated
Prevalence at birth	1-9 / 1 000 000	0.65	France	Validated
Prevalence at birth	1-5 / 10 000	11.7	Australia	Validated

Signs & symptoms

Clinical features (HPO)

29 HPO clinical features (Orphanet curated; top 29 by frequency):

HPO ID	Term	Frequency
HP:0000384	Preauricular skin tag	Very frequent (80-99%)
HP:0001140	Limbal dermoid	Very frequent (80-99%)
HP:0011332	Hemifacial hypoplasia	Very frequent (80-99%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000413	Atresia of the external auditory canal	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0002414	Spina bifida	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002937	Hemivertebrae	Frequent (30-79%)
HP:0008551	Microtia	Frequent (30-79%)
HP:0009117	Aplasia/Hypoplasia of the maxilla	Frequent (30-79%)
HP:0009118	Aplasia/Hypoplasia of the mandible	Frequent (30-79%)
HP:0012210	Abnormal renal morphology	Frequent (30-79%)
HP:0012758	Neurodevelopmental delay	Frequent (30-79%)
HP:0033792	Cross bite	Occasional (5-29%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000568	Microphthalmia	Occasional (5-29%)
HP:0000589	Coloboma	Occasional (5-29%)
HP:0000678	Dental crowding	Occasional (5-29%)
HP:0001511	Intrauterine growth retardation	Occasional (5-29%)
HP:0001561	Polyhydramnios	Occasional (5-29%)
HP:0001627	Abnormal heart morphology	Occasional (5-29%)
HP:0002308	Chiari malformation	Occasional (5-29%)
HP:0002781	Upper airway obstruction	Occasional (5-29%)
HP:0002870	Obstructive sleep apnea	Occasional (5-29%)
HP:0007370	Aplasia/Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0009892	Anotia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	craniofacial microsomia
Mondo ID	MONDO:0015397
MeSH	D006053
OMIM	164210
Orphanet	141132, 141136, 374
DOID	DOID:2907
NCIT	C84740
SNOMED CT	109393007, 367462009
UMLS	C0265240
MedGen	75554
GARD	0012074
Is cancer (heuristic)	no

Also known as: Expanded spectrum hemifacial microsomia · Expanded spectrum of hemifacial microsomia · facioauriculovertebral dysplasia · first branchial arch syndrome · Goldenhar disease · Goldenhar syndrome · hemifacial microsomia · HFM · Laterofacial microsomia · OAV dysplasia · OAV spectrum · OAVD · OAVS · oculo-auriculo-vertebral dysplasia · oculo-auriculo-vertebral spectrum · oculoauriculovertebral dysplasia · oculoauriculovertebral spectrum · oculoauriculovertebral syndrome · otomandibular syndrome · unilateral or bilateral and asymmetric otomandibular dysplasia

Data availability: 12 ClinVar variants · 14 GWAS associations (2 studies) · 3 GenCC gene-disease records · 1 cell line.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › craniofacial microsomia

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, 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 (2): craniofacial microsomia 1, craniofacial microsomia 2

Genetics & variants

GWAS landscape

14 GWAS associations across 2 studies. Top hits map to 12 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs13089920	2e-120	RN7SKP61 - MRPS17P3	A	5.18
rs10459648	1e-23	ARID3B	T	1.59
rs17802111	1e-17	Metazoa_SRP - EPAS1	C	1.48
rs11263613	4e-17	FGF3 - ANO1	G	1.68
rs3754648	5e-13	AGAP1	G	1.39
rs17090300	1e-11	LINC00392, LINC00393	G	2.31
rs7420812	7e-10	PARD3B	T	1.33
rs10905359	5e-09	LINC00708 - KRT8P37	A	1.32
rs62256696	2e-08	RN7SKP61 - MRPS17P3	C	0.96
rs3923380	8e-08	SHROOM3	A	1.28
rs754423	1e-07	NID2	C	1.27
rs4750407	2e-07	FRMD4A, FRMD4A-AS1	A	1.27
rs9574113	8e-06	EDNRB-AS1	G	1.27
rs7222240	9e-06	NMT1, DCAKD	G	1.73

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST004412	Zhang YB	2016	330	2,012	Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia.
GCST90832113	Kaprio L	2026	82	500,104	Genetic variation near ROBO1 is associated with craniofacial microsomia and related phenotypes in the Finnish population.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	13

MAF distribution

Bucket	Variants
common (>=0.05)	13
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	9
intergenic_variant	4
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs13089920	3	78503082	A>G	0.06	intergenic_variant	RN7SKP61 - MRPS17P3	2e-120	Tier 4: intronic/intergenic
rs10459648	15	74573099	C>A,G,T	0.49	intron_variant	ARID3B	1e-23	Tier 4: intronic/intergenic
rs17802111	2	46282518	C>G,T	0.37	intergenic_variant	Metazoa_SRP - EPAS1	1e-17	Tier 4: intronic/intergenic
rs11263613	11	69846566	G>A	0.12	intergenic_variant	FGF3 - ANO1	4e-17	Tier 4: intronic/intergenic
rs3754648	2	236112702	G>A,T	0.34	intron_variant	AGAP1	5e-13	Tier 4: intronic/intergenic
rs17090300	13	73583314	G>A	0.05	intron_variant	LINC00392, LINC00393	1e-11	Tier 4: intronic/intergenic
rs7420812	2	205570985	T>C	0.3	intron_variant	PARD3B	7e-10	Tier 4: intronic/intergenic
rs10905359	10	8407928	C>A	0.4	regulatory_region_variant	LINC00708 - KRT8P37	5e-09	Tier 3: regulatory
rs62256696	3	78515371	T>C	0.05	intergenic_variant	RN7SKP61 - MRPS17P3	2e-08	Tier 4: intronic/intergenic
rs3923380	4	76547441	C>A,G,T	0.44	intron_variant	SHROOM3	8e-08	Tier 4: intronic/intergenic
rs754423	14	52060469	C>A,T	0.47	intron_variant	NID2	1e-07	Tier 4: intronic/intergenic
rs4750407	10	13753471	A>G,T	0.3	intron_variant	FRMD4A, FRMD4A-AS1	2e-07	Tier 4: intronic/intergenic
rs9574113	13	77843996	A>G	0.23	intron_variant	EDNRB-AS1	8e-06	Tier 4: intronic/intergenic
rs7222240	17	45058827	G>A	0.02	intron_variant	NMT1, DCAKD	9e-06	Tier 4: intronic/intergenic

ClinVar germline variants

12 retrieved; paginated sample, class counts are floors:

9 likely pathogenic, 2 pathogenic/likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2431349	NM_001135649.3(FOXI3):c.700T>G (p.Phe234Val)	FOXI3	Pathogenic/Likely pathogenic	no assertion criteria provided
2431350	NM_001135649.3(FOXI3):c.702C>A (p.Phe234Leu)	FOXI3	Pathogenic/Likely pathogenic	no assertion criteria provided
3242435	NM_005483.3(CHAF1A):c.1604+1G>A	CHAF1A	Likely pathogenic	no assertion criteria provided
3242436	NM_005483.3(CHAF1A):c.1689_1690del (p.Cys563_Glu564delinsTer)	CHAF1A	Likely pathogenic	no assertion criteria provided
3242437	NM_005483.3(CHAF1A):c.876del (p.Thr293fs)	CHAF1A	Likely pathogenic	no assertion criteria provided
3242438	NM_005483.3(CHAF1A):c.1377+1G>A	CHAF1A	Likely pathogenic	no assertion criteria provided
3242439	NM_005483.3(CHAF1A):c.621_630dup (p.Thr211fs)	CHAF1A	Likely pathogenic	no assertion criteria provided
3242440	NM_005483.3(CHAF1A):c.2069G>A (p.Trp690Ter)	CHAF1A	Likely pathogenic	no assertion criteria provided
2431347	NM_001135649.3(FOXI3):c.305T>A (p.Phe102Tyr)	FOXI3	Likely pathogenic	no assertion criteria provided
2431348	NM_001135649.3(FOXI3):c.673T>C (p.Cys225Arg)	FOXI3	Likely pathogenic	no assertion criteria provided
1342295	NM_001257096.2(PAX1):c.1154_1157dup (p.Tyr386Ter)	PAX1	Likely pathogenic	no assertion criteria provided
2431340	NM_001135649.3(FOXI3):c.718C>T (p.Arg240Cys)	FOXI3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 25 · 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
AMIGO2	Limited	Autosomal dominant	craniofacial microsomia
EYA3	Limited	Autosomal dominant	craniofacial microsomia
MYT1	Limited	Autosomal dominant	craniofacial microsomia	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ROBO1	Orphanet:95496	Pituitary stalk interruption syndrome
CCND1	Orphanet:29073	Multiple myeloma
CCND1	Orphanet:52416	Mantle cell lymphoma
CCND1	Orphanet:67038	B-cell chronic lymphocytic leukemia
CCND1	Orphanet:892	Von Hippel-Lindau disease
FRMD4A	Orphanet:466688	Severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome
CYP11A1	Orphanet:168558	46,XY difference of sex development-adrenal insufficiency due to CYP11A1 deficiency
CYP11A1	Orphanet:289548	Inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency
EDC3	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
EFTUD2	Orphanet:79113	Mandibulofacial dysostosis-microcephaly syndrome
EDNRB	Orphanet:388	Hirschsprung disease
EDNRB	Orphanet:895	Waardenburg syndrome type 2
EDNRB	Orphanet:897	Waardenburg-Shah syndrome
DNAAF19	Orphanet:244	Primary ciliary dyskinesia
EPAS1	Orphanet:247511	Autosomal dominant secondary polycythemia
EPAS1	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
EPAS1	Orphanet:324299	Multiple paragangliomas associated with polycythemia
FGF3	Orphanet:2791	Otodental syndrome
FGF3	Orphanet:90024	Deafness with labyrinthine aplasia, microtia, and microdontia
FGF3	Orphanet:99806	Oculootodental syndrome
GATA3	Orphanet:2237	Hypoparathyroidism-sensorineural deafness-renal disease syndrome
GATA3	Orphanet:585936	B-lymphoblastic leukemia/lymphoma with hyperdiploidy
GFAP	Orphanet:363717	Alexander disease type I
GFAP	Orphanet:363722	Alexander disease type II
PAX1	Orphanet:2792	Otofaciocervical syndrome

Cohort genes → proteins

54 cohort genes, 51 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	48
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AMIGO2	HGNC:24073	ENSG00000139211	Q86SJ2	Amphoterin-induced protein 2	gencc
EYA3	HGNC:3521	ENSG00000158161	Q99504	Protein phosphatase EYA3	gencc
MYT1	HGNC:7622	ENSG00000196132	Q01538	Myelin transcription factor 1	gencc
ROBO1	HGNC:10249	ENSG00000169855	Q9Y6N7	Roundabout homolog 1	gwas
SCEL	HGNC:10573	ENSG00000136155	O95171	Sciellin	gwas
SEMA7A	HGNC:10741	ENSG00000138623	O75326	Semaphorin-7A	gwas
FMNL1	HGNC:1212	ENSG00000184922	O95466	Formin-like protein 1	gwas
NID2	HGNC:13389	ENSG00000087303	Q14112	Nidogen-2	gwas
ARID3B	HGNC:14350	ENSG00000179361	Q8IVW6	AT-rich interactive domain-containing protein 3B	gwas
PARD3B	HGNC:14446	ENSG00000116117	Q8TEW8	Partitioning defective 3 homolog B	gwas
CCND1	HGNC:1582	ENSG00000110092	P24385	G1/S-specific cyclin-D1	gwas
AGAP1	HGNC:16922	ENSG00000157985	Q9UPQ3	Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1	gwas
PRPF18	HGNC:17351	ENSG00000165630	Q99633	Pre-mRNA-splicing factor 18	gwas
LTO1	HGNC:17589	ENSG00000149716	Q8WV07	Protein LTO1 homolog	gwas
CHAF1A	HGNC:1910	ENSG00000167670	Q13111	Chromatin assembly factor 1 subunit A	clinvar
ASB18	HGNC:19770	ENSG00000182177	Q6ZVZ8	Ankyrin repeat and SOCS box protein 18	gwas
CLK3	HGNC:2071	ENSG00000179335	P49761	Dual specificity protein kinase CLK3	gwas
RTRAF	HGNC:23169	ENSG00000087302	Q9Y224	tRNA-splicing ligase complex subunit RTRAF	gwas
ACBD4	HGNC:23337	ENSG00000181513	Q8NC06	Acyl-CoA-binding domain-containing protein 4	gwas
C1QL1	HGNC:24182	ENSG00000131094	O75973	C1q-related factor	gwas
HEXIM1	HGNC:24953	ENSG00000186834	O94992	Protein HEXIM1	gwas
FRMD4A	HGNC:25491	ENSG00000151474	Q9P2Q2	FERM domain-containing protein 4A	gwas
CYP11A1	HGNC:2590	ENSG00000140459	P05108	Cholesterol side-chain cleavage enzyme, mitochondrial	gwas
EDC3	HGNC:26114	ENSG00000179151	Q96F86	Enhancer of mRNA-decapping protein 3	gwas
DCAKD	HGNC:26238	ENSG00000172992	Q8WVC6	Dephospho-CoA kinase domain-containing protein	gwas
SPATA32	HGNC:26349	ENSG00000184361	Q96LK8	Spermatogenesis-associated protein 32	gwas
CCDC158	HGNC:26374	ENSG00000163749	Q5M9N0	Coiled-coil domain-containing protein 158	gwas
SLAIN1	HGNC:26387	ENSG00000139737	Q8ND83	SLAIN motif-containing protein 1	gwas
CCDC33	HGNC:26552	ENSG00000140481	Q8N5R6	Coiled-coil domain-containing protein 33	gwas
KIF18B	HGNC:27102	ENSG00000186185	Q86Y91	Kinesin-like protein KIF18B	gwas
UBL7	HGNC:28221	ENSG00000138629	Q96S82	Ubiquitin-like protein 7	gwas
HEXIM2	HGNC:28591	ENSG00000168517	Q96MH2	Protein HEXIM2	gwas
SHROOM3	HGNC:30422	ENSG00000138771	Q8TF72	Protein Shroom3	gwas
EFTUD2	HGNC:30858	ENSG00000108883	Q15029	116 kDa U5 small nuclear ribonucleoprotein component	gwas
EDNRB	HGNC:3180	ENSG00000136160	P24530	Endothelin receptor type B	gwas
DNAAF19	HGNC:32700	ENSG00000167131	Q8IW40	Dynein axonemal assembly factor 19	gwas
EPAS1	HGNC:3374	ENSG00000116016	Q99814	Endothelial PAS domain-containing protein 1	gwas
FOXI3	HGNC:35123	ENSG00000214336	A8MTJ6	Forkhead box protein I3	clinvar
FGF19	HGNC:3675	ENSG00000162344	O95750	Fibroblast growth factor 19	gwas
FGF3	HGNC:3681	ENSG00000186895	P11487	Fibroblast growth factor 3	gwas
FGF4	HGNC:3682	ENSG00000075388	P08620	Fibroblast growth factor 4	gwas
GATA3	HGNC:4172	ENSG00000107485	P23771	Trans-acting T-cell-specific transcription factor GATA-3	gwas
GBX2	HGNC:4186	ENSG00000168505	P52951	Homeobox protein GBX-2	gwas
GFAP	HGNC:4235	ENSG00000131095	P14136	Glial fibrillary acidic protein	gwas
LINC00446	HGNC:42783	ENSG00000229249		long intergenic non-protein coding RNA 446	gwas
GNG2	HGNC:4404	ENSG00000186469	P59768	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	gwas
LINC00708	HGNC:44694	ENSG00000232170		long intergenic non-protein coding RNA 708	gwas
LINC01069	HGNC:49109	ENSG00000236133		long intergenic non-protein coding RNA 1069	gwas
KLF12	HGNC:6346	ENSG00000118922	Q9Y4X4	Krueppel-like factor 12	gwas
NMT1	HGNC:7857	ENSG00000136448	P30419	Glycylpeptide N-tetradecanoyltransferase 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AMIGO2	Amphoterin-induced protein 2	Required for depolarization-dependent survival of cultured cerebellar granule neurons.
EYA3	Protein phosphatase EYA3	Tyrosine phosphatase that specifically dephosphorylates ‘Tyr-142’ of histone H2AX (H2AXY142ph). ‘Tyr-142’ phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair…
MYT1	Myelin transcription factor 1	Binds to the promoter region of genes encoding proteolipid proteins of the central nervous system.
ROBO1	Roundabout homolog 1	Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuro…
SCEL	Sciellin	May function in the assembly or regulation of proteins in the cornified envelope.
SEMA7A	Semaphorin-7A	Plays an important role in integrin-mediated signaling and functions both in regulating cell migration and immune responses.
FMNL1	Formin-like protein 1	May play a role in the control of cell motility and survival of macrophages.
NID2	Nidogen-2	Cell adhesion glycoprotein which is widely distributed in basement membranes.
ARID3B	AT-rich interactive domain-containing protein 3B	Transcription factor which may be involved in neuroblastoma growth and malignant transformation.
PARD3B	Partitioning defective 3 homolog B	Putative adapter protein involved in asymmetrical cell division and cell polarization processes.
CCND1	G1/S-specific cyclin-D1	Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition.
AGAP1	Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1	GTPase-activating protein for ARF1 and, to a lesser extent, ARF5.
PRPF18	Pre-mRNA-splicing factor 18	Participates in the second step of pre-mRNA splicing.
LTO1	Protein LTO1 homolog	The complex LTO1:YAE1 functions as a target specific adapter that probably recruits apo-ABCE1 to the cytosolic iron-sulfur protein assembly (CIA) complex machinery.
CHAF1A	Chromatin assembly factor 1 subunit A	Acts as a component of the histone chaperone complex chromatin assembly factor 1 (CAF-1), which assembles histone octamers onto DNA during replication and repair.
ASB18	Ankyrin repeat and SOCS box protein 18	May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
CLK3	Dual specificity protein kinase CLK3	Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates.
RTRAF	tRNA-splicing ligase complex subunit RTRAF	Accessory subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the mature tRNA as a canonical 3’,5’-phosph…
ACBD4	Acyl-CoA-binding domain-containing protein 4	Binds medium- and long-chain acyl-CoA esters and may function as an intracellular carrier of acyl-CoA esters.
C1QL1	C1q-related factor	May regulate the number of excitatory synapses that are formed on hippocampus neurons.
HEXIM1	Protein HEXIM1	Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor.
FRMD4A	FERM domain-containing protein 4A	Scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex.
CYP11A1	Cholesterol side-chain cleavage enzyme, mitochondrial	A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones.
EDC3	Enhancer of mRNA-decapping protein 3	Binds single-stranded RNA.
CCDC158	Coiled-coil domain-containing protein 158	Plays a role in receptor-mediated endocytosis in proximal tubular cells of the kidney.
SLAIN1	SLAIN motif-containing protein 1	Microtubule plus-end tracking protein that might be involved in the regulation of cytoplasmic microtubule dynamics, microtubule organization and microtubule elongation.
KIF18B	Kinesin-like protein KIF18B	In complex with KIF2C, constitutes the major microtubule plus-end depolymerizing activity in mitotic cells.
UBL7	Ubiquitin-like protein 7	Interferon-stimulated protein that positively regulates RNA virus-triggered innate immune signaling.
HEXIM2	Protein HEXIM2	Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor.
SHROOM3	Protein Shroom3	Controls cell shape changes in the neuroepithelium during neural tube closure.
EFTUD2	116 kDa U5 small nuclear ribonucleoprotein component	Required for pre-mRNA splicing as component of the spliceosome, including pre-catalytic, catalytic and post-catalytic spliceosomal complexes.
EDNRB	Endothelin receptor type B	Non-specific receptor for endothelin 1, 2, and 3.
DNAAF19	Dynein axonemal assembly factor 19	Dynein-attachment factor required for cilia motility.
EPAS1	Endothelial PAS domain-containing protein 1	Transcription factor involved in the induction of oxygen regulated genes.
FOXI3	Forkhead box protein I3	Transcription factor required for pharyngeal arch development, which is involved in hair, ear, jaw and dental development.
FGF19	Fibroblast growth factor 19	Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades.
FGF3	Fibroblast growth factor 3	Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation.
FGF4	Fibroblast growth factor 4	Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation.
GATA3	Trans-acting T-cell-specific transcription factor GATA-3	Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes.
GBX2	Homeobox protein GBX-2	May act as a transcription factor for cell pluripotency and differentiation in the embryo.
GFAP	Glial fibrillary acidic protein	GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells.
GNG2	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems.
KLF12	Krueppel-like factor 12	Confers strong transcriptional repression to the AP-2-alpha gene.
NMT1	Glycylpeptide N-tetradecanoyltransferase 1	Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins.
NRP2	Neuropilin-2	High affinity receptor for semaphorins 3C, 3F, VEGF-165 and VEGF-145 isoforms of VEGF, and the PLGF-2 isoform of PGF.
PAX1	Paired box protein Pax-1	This protein is a transcriptional activator.
PLCD3	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3	Hydrolyzes the phosphatidylinositol 4,5-bisphosphate (PIP2) to generate 2 second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3).
PRKCE	Protein kinase C epsilon type	Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motil…

Protein-family classification

Druggable: 9 · Difficult: 13 · Unknown: 32 · Druggable fraction: 0.17

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
Antibody/Immunoglobulin	3	1.6×	0.499
Scaffold/PPI	5	1.6×	0.499
Kinase	3	1.5×	0.499
Transcription factor	8	1.2×	0.499
Other/Unknown	32	1.1×	0.499
Enzyme (other)	2	0.4×	0.947
GPCR	1	0.4×	0.947

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AMIGO2	Antibody/Immunoglobulin	yes		Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
EYA3	Other/Unknown	no		EYA_dom, EYA, EYA_dom_sf
MYT1	Transcription factor	no		Znf_C2H2C, Myelin_TF, Znf_C2H2C_sf
ROBO1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
SCEL	Transcription factor	no		Znf_LIM, Cell_Prolif/Cornif_Regul
SEMA7A	Antibody/Immunoglobulin	yes		Semap_dom, Plexin_repeat, Ig-like_dom
FMNL1	Other/Unknown	no		FH3_dom, GTPase-bd, ARM-like
NID2	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, Thyroglobulin_1
ARID3B	Other/Unknown	no		ARID_dom, REKLES_domain, ARID_dom_sf
PARD3B	Scaffold/PPI	no		PDZ, Par3/HAL_N, PDZ_sf
CCND1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
AGAP1	Scaffold/PPI	no		ArfGAP_dom, Small_GTPase, PH_domain
PRPF18	Other/Unknown	no		Prp18, PRP4-like, PRP4-like_sf
LTO1	Other/Unknown	no		Essential_protein_Yae1_N, LTO1_adapter
CHAF1A	Other/Unknown	no		CAF-1_p150_acidic, CAF1A_DD, CAF1_p150_N
ASB18	Scaffold/PPI	no		SOCS_box, Ankyrin_rpt, SOCS_box-like_dom_sf
CLK3	Kinase	yes	2.7.12.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
RTRAF	Other/Unknown	no		RTRAF
ACBD4	Other/Unknown	no		Acyl-CoA-binding_protein, FERM/acyl-CoA-bd_prot_sf, Acyl-CoA-binding_prot_CS
C1QL1	Other/Unknown	no		C1q_dom, Collagen, Tumour_necrosis_fac-like_dom
HEXIM1	Other/Unknown	no		HEXIM
FRMD4A	Other/Unknown	no		FERM_domain, PH-like_dom_sf, FERM/acyl-CoA-bd_prot_sf
CYP11A1	Enzyme (other)	yes	1.14.15.6	Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
EDC3	Other/Unknown	no		YjeF_N_dom, FDF_dom, Lsm14-like_N
DCAKD	Kinase	yes		Depp_CoAkinase, P-loop_NTPase
SPATA32	Other/Unknown	no		SPATA32
CCDC158	Other/Unknown	no		CCDC158
SLAIN1	Other/Unknown	no		Slain
CCDC33	Other/Unknown	no		C2_dom, C2_domain_sf, CCD33
KIF18B	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
UBL7	Other/Unknown	no		Ubiquitin-like_dom, UBA-like_sf, Ubiquilin
HEXIM2	Other/Unknown	no		HEXIM
SHROOM3	Scaffold/PPI	no		PDZ, ASD2_dom, ASD1_dom
EFTUD2	Other/Unknown	no		EFG_V-like, T_Tr_GTP-bd_dom, EFTu-like_2
EDNRB	GPCR	yes		GPCR_Rhodpsn, Endthln_rcpt, ETB_rcpt
DNAAF19	Other/Unknown	no		RPAP3-like_C, Dynein_attach_N, CC103
EPAS1	Transcription factor	no		PAS, Nuc_translocat, PAC
FOXI3	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
FGF19	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF, FGF15/19/21
FGF3	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF
FGF4	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF
GATA3	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, TF_GATA-2/3
GBX2	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
GFAP	Other/Unknown	no		Intermed_filament_DNA-bd, IF_conserved, IF_rod_dom
LINC00446	Other/Unknown	no
GNG2	Other/Unknown	no		G-protein_gamma, G-protein_gamma-like_dom, GGL_sf
LINC00708	Other/Unknown	no
LINC01069	Other/Unknown	no
KLF12	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
NMT1	Enzyme (other)	yes	2.3.1.97	NMT, Acyl_CoA_acyltransferase, NMT_N

Expression context

Cohort genes with no expression data: 0.

43 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)	3
broad (>20)	51
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	8
sural nerve	7
male germ line stem cell (sensu Vertebrata) in testis	7
ventricular zone	6
primordial germ cell in gonad	6
ganglionic eminence	5
granulocyte	4
cortical plate	4
tibia	3
oocyte	3
secondary oocyte	3
apex of heart	3
esophagus squamous epithelium	2
pigmented layer of retina	2
cerebellar cortex	2
lower esophagus mucosa	2
upper leg skin	2
C1 segment of cervical spinal cord	2
primary visual cortex	2
monocyte	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AMIGO2	271	ubiquitous	marker	blood vessel layer, germinal epithelium of ovary, renal glomerulus
EYA3	259	ubiquitous	marker	esophagus squamous epithelium, pigmented layer of retina, renal medulla
MYT1	101	broad	yes	ganglionic eminence, cerebellum, cerebellar cortex
ROBO1	287	ubiquitous	marker	ventricular zone, ganglionic eminence, tibia
SCEL	183	tissue_specific	marker	tongue squamous epithelium, lower esophagus mucosa, upper leg skin
SEMA7A	136	ubiquitous	yes	spleen, C1 segment of cervical spinal cord, primary visual cortex
FMNL1	236	ubiquitous	marker	granulocyte, monocyte, leukocyte
NID2	236	ubiquitous	marker	cartilage tissue, stromal cell of endometrium, tibia
ARID3B	212	ubiquitous	marker	oocyte, primordial germ cell in gonad, type B pancreatic cell
PARD3B	200	ubiquitous	marker	sural nerve, cardiac muscle of right atrium, ventricular zone
CCND1	280	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, upper arm skin
AGAP1	287	ubiquitous	marker	frontal pole, cortical plate, paraflocculus
PRPF18	134	ubiquitous	marker	calcaneal tendon, corpus callosum, sural nerve
LTO1	180	ubiquitous	yes	right hemisphere of cerebellum, cerebellar hemisphere, granulocyte
CHAF1A	270	ubiquitous	marker	secondary oocyte, sural nerve, ventricular zone
ASB18	54		marker	apex of heart, male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle
CLK3	276	ubiquitous	marker	lower esophagus mucosa, granulocyte, left testis
RTRAF	288	ubiquitous	marker	secondary oocyte, oocyte, primordial germ cell in gonad
ACBD4	200	ubiquitous	yes	right lobe of liver, mucosa of stomach, small intestine Peyer’s patch
C1QL1	186	broad	marker	paraflocculus, middle frontal gyrus, Brodmann (1909) area 10
HEXIM1	290	ubiquitous	marker	esophagus squamous epithelium, granulocyte, gingival epithelium
FRMD4A	272	ubiquitous	marker	sural nerve, ganglionic eminence, oocyte
CYP11A1	136	broad	marker	adrenal tissue, right adrenal gland, right adrenal gland cortex
EDC3	204	ubiquitous	marker	left testis, right testis, cortical plate
DCAKD	220	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
SPATA32	79	tissue_specific	yes	mucosa of paranasal sinus, left testis, male germ line stem cell (sensu Vertebrata) in testis
CCDC158	151		marker	sperm, left testis, right testis
SLAIN1	216	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
CCDC33	100	broad	marker	right uterine tube, olfactory segment of nasal mucosa, left testis
KIF18B	186	ubiquitous	marker	trabecular bone tissue, ventricular zone, cervix squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 22.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EFTUD2	8,471
CCND1	8,328
GFAP	6,997
GATA3	5,990
EPAS1	4,652
FGF3	4,085
FGF4	4,019
UBL7	3,664
HEXIM1	3,613
EDC3	2,714

Intra-cohort edges

A	B	Sources
ACBD4	DCAKD	string_interaction
AGAP1	ASB18	string_interaction
AGAP1	GBX2	string_interaction
ARID3B	KLF12	biogrid_interaction
ARID3B	UBL7	string_interaction
CCDC33	CLK3	string_interaction
CCDC33	UBL7	string_interaction
CCND1	LTO1	string_interaction
CLK3	UBL7	string_interaction
DCAKD	HEXIM2	string_interaction
DCAKD	NMT1	string_interaction
DCAKD	PLCD3	string_interaction
DCAKD	SPATA32	string_interaction
EDNRB	SLAIN1	string_interaction
FGF19	FGF4	string_interaction
FGF19	LTO1	string_interaction
FGF3	LTO1	string_interaction
FGF4	LTO1	string_interaction
FGF4	NID2	biogrid_interaction, intact
FOXI3	PAX1	string_interaction
HEXIM1	HEXIM2	biogrid_interaction, intact, string_interaction
NRP2	SEMA7A	string_interaction

Structural data

PDB: 28 · AlphaFold-only: 23 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNG2	P59768	1,252
EFTUD2	Q15029	68
NMT1	P30419	52
EPAS1	Q99814	43
CLK3	P49761	22
EDNRB	P24530	18
NRP2	O60462	16
ROBO1	Q9Y6N7	12
CCND1	P24385	11
CHAF1A	Q13111	11
EDC3	Q96F86	6
CYP11A1	P05108	4
FGF19	O95750	4
GATA3	P23771	3
EYA3	Q99504	2
AGAP1	Q9UPQ3	2
HEXIM1	O94992	2
UBL7	Q96S82	2
SHROOM3	Q8TF72	2
PRKCE	Q02156	2
MYT1	Q01538	1
SEMA7A	O75326	1
FMNL1	O95466	1
PRPF18	Q99633	1
RTRAF	Q9Y224	1
ACBD4	Q8NC06	1
FGF4	P08620	1
GFAP	P14136	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DCAKD	Q8WVC6	94.62
PLCD3	Q8N3E9	85.51
LTO1	Q8WV07	85.08
ASB18	Q6ZVZ8	80.50
DNAAF19	Q8IW40	80.42
FGF3	P11487	79.32
C1QL1	O75973	79.26
AMIGO2	Q86SJ2	75.93
NID2	Q14112	74.40
CCDC158	Q5M9N0	73.43
CCDC33	Q8N5R6	72.34
HEXIM2	Q96MH2	72.34
GBX2	P52951	63.07
KIF18B	Q86Y91	62.96
FRMD4A	Q9P2Q2	62.95
ARID3B	Q8IVW6	59.11
FOXI3	A8MTJ6	59.00
PARD3B	Q8TEW8	55.56
PAX1	P15863	55.21
SLAIN1	Q8ND83	54.80
KLF12	Q9Y4X4	51.57
SCEL	O95171	45.48
SPATA32	Q96LK8	42.23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 210. Enrichment computed across 54 evidence-associated genes (29 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 29 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
FGFRL1 modulation of FGFR1 signaling	2	60.6×	0.020	FGF3, FGF4
FGFR4 ligand binding and activation	2	56.3×	0.020	FGF19, FGF4
Phospholipase C-mediated cascade; FGFR4	2	52.5×	0.020	FGF19, FGF4
Activated point mutants of FGFR2	2	46.3×	0.020	FGF3, FGF4
Phospholipase C-mediated cascade: FGFR1	2	46.3×	0.020	FGF3, FGF4
Phospholipase C-mediated cascade; FGFR2	2	43.8×	0.020	FGF3, FGF4
Specification of the neural plate border	2	43.8×	0.020	FGF4, GBX2
PI-3K cascade:FGFR4	2	39.4×	0.020	FGF19, FGF4
Downstream signaling of activated FGFR1	2	37.5×	0.020	FGF3, FGF4
SHC-mediated cascade:FGFR4	2	37.5×	0.020	FGF19, FGF4
PI-3K cascade:FGFR1	2	35.8×	0.020	FGF3, FGF4
SHC-mediated cascade:FGFR1	2	34.2×	0.020	FGF3, FGF4
PI-3K cascade:FGFR2	2	34.2×	0.020	FGF3, FGF4
FRS-mediated FGFR4 signaling	2	34.2×	0.020	FGF19, FGF4
PI3K Cascade	3	28.1×	0.020	FGF19, FGF3, FGF4
Constitutive Signaling by Aberrant PI3K in Cancer	3	13.1×	0.020	FGF19, FGF3, FGF4
SHC-mediated cascade:FGFR2	2	32.8×	0.021	FGF3, FGF4
FRS-mediated FGFR1 signaling	2	31.5×	0.021	FGF3, FGF4
FRS-mediated FGFR2 signaling	2	30.3×	0.022	FGF3, FGF4
Negative regulation of FGFR4 signaling	2	28.1×	0.024	FGF19, FGF4
Negative regulation of FGFR1 signaling	2	25.4×	0.026	FGF3, FGF4
Negative regulation of FGFR2 signaling	2	25.4×	0.026	FGF3, FGF4
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	3	10.0×	0.029	FGF19, FGF3, FGF4
Signaling by FGFR2 in disease	2	18.3×	0.046	FGF3, FGF4
G alpha (z) signalling events	2	16.1×	0.057	GNG2, PRKCE
betaKlotho-mediated ligand binding	1	131.3×	0.061	FGF19
PIP3 activates AKT signaling	3	6.9×	0.070	FGF19, FGF3, FGF4
Neuropilin interactions with VEGF and VEGFR	1	98.5×	0.071	NRP2
Activation, myristolyation of BID and translocation to mitochondria	1	98.5×	0.071	NMT1
SLIT2:ROBO1 increases RHOA activity	1	98.5×	0.071	ROBO1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 50 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
neural crest cell migration	5	33.7×	2e-04	SEMA7A, EDNRB, FGF19, GBX2, GFAP
negative regulation of mammary gland epithelial cell proliferation	2	134.8×	0.019	ROBO1, GATA3
parathyroid gland development	2	96.3×	0.027	FOXI3, GATA3
anatomical structure morphogenesis	4	11.1×	0.041	FOXI3, EYA3, FGF3, GATA3
positive regulation of MAPK cascade	5	8.1×	0.041	ROBO1, FGF19, FGF3, FGF4, PRKCE
fibroblast growth factor receptor signaling pathway	3	17.1×	0.053	FGF19, FGF3, FGF4
type IV hypersensitivity	1	337.0×	0.054	GATA3
toxin catabolic process	1	337.0×	0.054	PRKCE
positive regulation of Schwann cell proliferation	1	337.0×	0.054	GFAP
olfactory lobe development	1	337.0×	0.054	SEMA7A
enteric smooth muscle cell differentiation	1	337.0×	0.054	EDNRB
steroid hormone biosynthetic process	1	337.0×	0.054	CYP11A1
response to endothelin	1	337.0×	0.054	EDNRB
obsolete negative regulation of cell proliferation involved in mesonephros development	1	337.0×	0.054	GATA3
regulation of cellular response to X-ray	1	337.0×	0.054	GATA3
obsolete negative regulation of fibroblast growth factor receptor signaling pathway involved in ureteric bud formation	1	337.0×	0.054	GATA3
obsolete negative regulation of glial cell-derived neurotrophic factor receptor signaling pathway involved in ureteric bud formation	1	337.0×	0.054	GATA3
enteric nervous system development	2	39.6×	0.054	EDNRB, GFAP
cellular response to prostaglandin E stimulus	2	33.7×	0.054	GNG2, PRKCE
pharyngeal system development	2	32.1×	0.054	FOXI3, GATA3
embryo development ending in birth or egg hatching	2	29.3×	0.054	SCEL, PAX1
outflow tract septum morphogenesis	2	25.9×	0.054	ROBO1, NRP2
negative chemotaxis	2	25.9×	0.054	SEMA7A, NRP2
neurogenesis	3	12.5×	0.054	FGF19, FGF3, FGF4
axon guidance	4	7.2×	0.054	SEMA7A, GATA3, GBX2, NRP2
generation of catalytic spliceosome for second transesterification step	1	168.5×	0.056	PRPF18
pro-T cell differentiation	1	168.5×	0.056	GATA3
posterior midgut development	1	168.5×	0.056	EDNRB
negative regulation of neuron maturation	1	168.5×	0.056	EDNRB
N-terminal peptidyl-glycine N-myristoylation	1	168.5×	0.056	NMT1

Therapeutics

Drug target analysis

Approved (phase 4): 8 · Phase ≥3: 8 · Phased (≥1): 12 · Undrugged: 42

Druggability breadth: 18 of 54 evidence-associated genes (33%) 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
EYA3	BENZARONE
MYT1	DASATINIB ANHYDROUS
CCND1	PALBOCICLIB
CLK3	ALECTINIB
CYP11A1	AMINOGLUTETHIMIDE
EDNRB	AMBRISENTAN
EPAS1	BELZUTIFAN
PRKCE	INGENOL MEBUTATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CCND1	35	4
CLK3	23	4
PRKCE	21	4
EDNRB	16	4
EPAS1	7	4
EYA3	4	4
MYT1	4	4
CYP11A1	1	4
KIF18B	1	2
EFTUD2	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BENZARONE	4	EYA3
BENZIODARONE	4	EYA3
BENZBROMARONE	4	EYA3
DASATINIB ANHYDROUS	4	MYT1
DASATINIB	4	MYT1
PALBOCICLIB	4	CCND1
ABEMACICLIB	4	CCND1, CLK3
RIBOCICLIB	4	CCND1
TRILACICLIB	4	CCND1
ALECTINIB	4	CLK3
BOSUTINIB	4	CLK3, PRKCE
MIDOSTAURIN	4	CLK3, PRKCE
AMINOGLUTETHIMIDE	4	CYP11A1
AMBRISENTAN	4	EDNRB
MODAFINIL	4	EDNRB
MACITENTAN	4	EDNRB
APROCITENTAN	4	EDNRB
SITAXENTAN	4	EDNRB
SULFISOXAZOLE	4	EDNRB
MAZINDOL	4	EDNRB
BOSENTAN	4	EDNRB
BELZUTIFAN	4	EPAS1
EMETINE	4	EPAS1
DOXORUBICIN	4	EPAS1
TOPOTECAN	4	EPAS1
INGENOL MEBUTATE	4	PRKCE
TAMOXIFEN	4	PRKCE
FEDRATINIB	4	PRKCE
RUXOLITINIB	4	PRKCE
DINACICLIB	3	CCND1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
PRKCE	722	Binding:707, Functional:14, ADMET:1
CCND1	576	Binding:574, Functional:1, ADMET:1
CLK3	294	Binding:292, Functional:2
EDNRB	270	Binding:229, Functional:41
EPAS1	241	Binding:233, Functional:8
NMT1	93	Binding:75, ADMET:18
EYA3	15	Binding:15
GNG2	11	Binding:11
MYT1	9	Binding:9
HEXIM1	8	Binding:8
EFTUD2	8	Binding:8
FMNL1	7	Binding:7
KIF18B	6	Binding:6
NRP2	3	Binding:3
RTRAF	1	Binding:1
CYP11A1	1	Functional:1
SHROOM3	1	Binding:1
FGF4	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CLK3	2.7.12.1	dual-specificity kinase
CYP11A1	1.14.15.6	cholesterol monooxygenase (side-chain-cleaving)
NMT1	2.3.1.97	glycylpeptide N-tetradecanoyltransferase
PRKCE	2.7.11.13	protein kinase C

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CCND1	576
CLK3	294
EDNRB	270
EPAS1	241
PRKCE	722

Pharmacogenomics

Cohort genes with a PharmGKB record: 51; 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)
BENZARONE	4	EYA3
BENZIODARONE	4	EYA3
BENZBROMARONE	4	EYA3
DASATINIB ANHYDROUS	4	MYT1
DASATINIB	4	MYT1
PALBOCICLIB	4	CCND1
ABEMACICLIB	4	CCND1, CLK3
RIBOCICLIB	4	CCND1
TRILACICLIB	4	CCND1
ALECTINIB	4	CLK3
BOSUTINIB	4	CLK3, PRKCE
MIDOSTAURIN	4	CLK3, PRKCE
AMINOGLUTETHIMIDE	4	CYP11A1
AMBRISENTAN	4	EDNRB
MODAFINIL	4	EDNRB
MACITENTAN	4	EDNRB
APROCITENTAN	4	EDNRB
SITAXENTAN	4	EDNRB
SULFISOXAZOLE	4	EDNRB
MAZINDOL	4	EDNRB
BOSENTAN	4	EDNRB
BELZUTIFAN	4	EPAS1
EMETINE	4	EPAS1
DOXORUBICIN	4	EPAS1
TOPOTECAN	4	EPAS1
INGENOL MEBUTATE	4	PRKCE
TAMOXIFEN	4	PRKCE
FEDRATINIB	4	PRKCE
RUXOLITINIB	4	PRKCE
DINACICLIB	3	CCND1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	8	EYA3, MYT1, CCND1, CLK3, CYP11A1, EDNRB, EPAS1, PRKCE
B	Phased (≥1) drug, not yet approved	4	KIF18B, EFTUD2, GNG2, NMT1
C	Druggable family + PDB, no drug	2	ROBO1, SEMA7A
D	Druggable family + AlphaFold only, no drug	2	AMIGO2, DCAKD
E	Difficult family or no structure, no drug	38	SCEL, FMNL1, NID2, ARID3B, PARD3B, AGAP1, PRPF18, LTO1, CHAF1A, ASB18 (+28 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DCAKD	0	NMT1
AMIGO2	0	—
ROBO1	0	—
SCEL	0	—
SEMA7A	0	—
FMNL1	7	—
NID2	0	—
ARID3B	0	—
PARD3B	0	—
AGAP1	0	—
PRPF18	0	—
LTO1	0	—
CHAF1A	0	—
ASB18	0	—
RTRAF	1	—
ACBD4	0	—
C1QL1	0	—
HEXIM1	8	—
FRMD4A	0	—
EDC3	0	—
SPATA32	0	—
CCDC158	0	—
SLAIN1	0	—
CCDC33	0	—
UBL7	0	—
HEXIM2	0	—
SHROOM3	1	—
DNAAF19	0	—
FOXI3	0	—
FGF19	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 10.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01674439	PHASE2	COMPLETED	Clinical Trial of Fat Grafts Supplemented With Adipose-derived Regenerative Cells
NCT05610878	PHASE1	RECRUITING	Efficacy of Preconditioned Adipose-Derived Stem Cells in Fat Grafting
NCT02224677	Not specified	COMPLETED	Craniofacial Microsomia: Longitudinal Outcomes in Children Pre-Kindergarten (CLOCK)
NCT02494752	Not specified	UNKNOWN	Role of Mesenchymal Stem Cells in Fat Grafting
NCT03806361	Not specified	COMPLETED	Fat Grafts With Adipose-derived Regenerative Cells for Soft Tissue Reconstruction in Children
NCT03861650	Not specified	COMPLETED	Evaluation of Effect of Bone Marrow Aspirate Concentrate on Distracted Mandibular Bone Properties
NCT03869021	Not specified	COMPLETED	Computer Guided for Mandibular Distraction Osteogenesis
NCT04056858	Not specified	COMPLETED	Study of a Candidate Gene Involved in Goldenhar Syndrome.
NCT04351893	Not specified	COMPLETED	Craniofacial Microsomia: Accelerating Understanding of the Significance and Etiology
NCT04931056	Not specified	COMPLETED	A Post Market Clinical Follow-up Study on Biomet Microfixation HTR PEKK (Midface), Facial & Mandibular Plates.