Meier-Gorlin syndrome

Summary

Meier-Gorlin syndrome (MONDO:0016817) is a disease (an umbrella term covering 10 Mondo subtypes) caused by GINS3 (GenCC Strong), with 13 cohort genes and 1 clinical trial. The dominant Reactome pathway is Activation of the pre-replicative complex (9 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: GINS3 (GenCC Strong)
• Umbrella term: 10 Mondo subtypes
• Cohort genes: 13
• ClinVar variants: 16
• Phenotypes (HPO): 49
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		67	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

49 HPO clinical features (Orphanet curated; top 49 by frequency):

HPO ID	Term	Frequency
HP:0001382	Joint hypermobility	Very frequent (80-99%)
HP:0000160	Narrow mouth	Very frequent (80-99%)
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0000278	Retrognathia	Very frequent (80-99%)
HP:0000347	Micrognathia	Very frequent (80-99%)
HP:0000356	Abnormality of the outer ear	Very frequent (80-99%)
HP:0000413	Atresia of the external auditory canal	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0001510	Growth delay	Very frequent (80-99%)
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)
HP:0002750	Delayed skeletal maturation	Very frequent (80-99%)
HP:0003100	Slender long bone	Very frequent (80-99%)
HP:0003510	Severe short stature	Very frequent (80-99%)
HP:0004209	Clinodactyly of the 5th finger	Very frequent (80-99%)
HP:0005930	Abnormality of epiphysis morphology	Very frequent (80-99%)
HP:0009892	Anotia	Very frequent (80-99%)
HP:0009939	Mandibular aplasia	Very frequent (80-99%)
HP:0011267	Microtia, third degree	Very frequent (80-99%)
HP:0011968	Feeding difficulties	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Very frequent (80-99%)
HP:0000059	Hypoplastic labia majora	Frequent (30-79%)
HP:0000060	Clitoral hypoplasia	Frequent (30-79%)
HP:0000064	Hypoplastic labia minora	Frequent (30-79%)
HP:0000327	Hypoplasia of the maxilla	Frequent (30-79%)
HP:0000358	Posteriorly rotated ears	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000772	Abnormal rib morphology	Frequent (30-79%)
HP:0001363	Craniosynostosis	Frequent (30-79%)
HP:0002094	Dyspnea	Frequent (30-79%)
HP:0002098	Respiratory distress	Frequent (30-79%)
HP:0002705	High, narrow palate	Frequent (30-79%)
HP:0002878	Respiratory failure	Frequent (30-79%)
HP:0006443	Patellar aplasia	Frequent (30-79%)
HP:0006660	Aplastic clavicles	Frequent (30-79%)
HP:0008665	Clitoral hypertrophy	Frequent (30-79%)
HP:0100490	Camptodactyly of finger	Frequent (30-79%)
HP:0000039	Epispadias	Occasional (5-29%)
HP:0000047	Hypospadias	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000176	Submucous cleft hard palate	Occasional (5-29%)
HP:0000193	Bifid uvula	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001328	Specific learning disability	Occasional (5-29%)
HP:0003042	Elbow dislocation	Occasional (5-29%)
HP:0008736	Hypoplasia of penis	Occasional (5-29%)
HP:0012471	Thick vermilion border	Occasional (5-29%)
HP:0100783	Breast aplasia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Meier-Gorlin syndrome
Mondo ID	MONDO:0016817
MeSH	C538012
OMIM	224690
Orphanet	2554
DOID	DOID:0060306
UMLS	C1868684
MedGen	401501
GARD	0002033
MedDRA	10070612
NORD	1077
Is cancer (heuristic)	no

Also known as: ear-patella-short stature syndrome · Meier-Gorlin syndrome

Data availability: 16 ClinVar variants · 10 GenCC gene-disease records.

Disease family

An umbrella term covering 10 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › Meier-Gorlin 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, 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 (10): Meier-Gorlin syndrome 1, Meier-Gorlin syndrome 2, Meier-Gorlin syndrome 3, Meier-Gorlin syndrome 4, Meier-Gorlin syndrome 5, Meier-Gorlin syndrome 6, Meier-Gorlin syndrome 7, Meier-Gorlin syndrome 8, Meier-Gorlin syndrome 9, Meier-Gorlin syndrome 10

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

16 retrieved; paginated sample, class counts are floors:

9 pathogenic, 3 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
30498	NM_030928.4(CDT1):c.1385G>A (p.Arg462Gln)	CDT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1173053	NM_017613.4(DONSON):c.631C>T (p.Arg211Cys)	DONSON	Pathogenic	criteria provided, single submitter
1173054	NM_017613.4(DONSON):c.1634C>T (p.Pro545Leu)	DONSON	Pathogenic	criteria provided, single submitter
1173061	NM_017613.4(DONSON):c.494T>C (p.Phe165Ser)	DONSON	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1173062	NM_017613.4(DONSON):c.607-36G>A	DONSON	Pathogenic	criteria provided, single submitter
203999	NM_015895.5(GMNN):c.16A>T (p.Lys6Ter)	GMNN	Pathogenic	criteria provided, single submitter
204000	NM_015895.5(GMNN):c.35_38del (p.Ile12fs)	GMNN	Pathogenic	criteria provided, single submitter
1173057	NM_005916.5(MCM7):c.415C>T (p.Gln139Ter)	MCM7	Pathogenic	criteria provided, single submitter
1173058	NM_005916.5(MCM7):c.1616A>G (p.Tyr539Cys)	MCM7	Pathogenic	criteria provided, single submitter
1173069	NM_005916.5(MCM7):c.776G>C (p.Gly259Ala)	MCM7	Pathogenic	criteria provided, multiple submitters, no conflicts
1173070	NM_005916.5(MCM7):c.1579C>T (p.Arg527Ter)	MCM7	Pathogenic	criteria provided, single submitter
30232	NM_004153.4(ORC1):c.314G>A (p.Arg105Gln)	ORC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
204001	NM_015895.5(GMNN):c.50A>G (p.Lys17Arg)	GMNN	Likely pathogenic	criteria provided, single submitter
1012222	NM_017613.4(DONSON):c.670C>T (p.Pro224Ser)	DONSON	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1012223	NM_017613.4(DONSON):c.809A>G (p.Tyr270Cys)	DONSON	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1173065	NM_002388.6(MCM3):c.2282A>T (p.Gln761Leu)	MCM3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 47 · Orphanet: 11 · 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
CDC45	Definitive	Autosomal recessive	Meier-Gorlin syndrome 7	4
CDC6	Definitive	Autosomal recessive	Meier-Gorlin syndrome 5	5
CDT1	Definitive	Autosomal recessive	Meier-Gorlin syndrome 4	4
ORC1	Definitive	Autosomal recessive	Meier-Gorlin syndrome 1	5
ORC4	Definitive	Autosomal recessive	Meier-Gorlin syndrome 2	6
ORC6	Definitive	Autosomal recessive	Meier-Gorlin syndrome 3	5
SLC25A15	Definitive	Autosomal recessive	Meier-Gorlin syndrome 1	10
GINS3	Strong	Autosomal recessive	Meier-Gorlin syndrome	2
GMNN	Strong	Autosomal dominant	Meier-Gorlin syndrome 6	5
GINS2	Limited	Autosomal recessive	Meier-Gorlin syndrome

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC25A15	Orphanet:415	Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome
GMNN	Orphanet:2554	Ear-patella-short stature syndrome
CDT1	Orphanet:2554	Ear-patella-short stature syndrome
ORC1	Orphanet:2554	Ear-patella-short stature syndrome
ORC6	Orphanet:2554	Ear-patella-short stature syndrome
CDC45	Orphanet:2554	Ear-patella-short stature syndrome
CDC6	Orphanet:2554	Ear-patella-short stature syndrome
ORC4	Orphanet:2554	Ear-patella-short stature syndrome
DONSON	Orphanet:572768	Microcephaly-micromelia syndrome
DONSON	Orphanet:572773	Microcephaly-short stature-limb abnormalities syndrome
MCM7	Orphanet:2512	Autosomal recessive primary microcephaly

Cohort genes → proteins

13 cohort genes, 13 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	13

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC25A15	HGNC:10985	ENSG00000102743	Q9Y619	Mitochondrial ornithine transporter 1	gencc,clinvar
GMNN	HGNC:17493	ENSG00000112312	O75496	Geminin	gencc,clinvar
CDT1	HGNC:24576	ENSG00000167513	Q9H211	DNA replication factor Cdt1	gencc,clinvar
ORC1	HGNC:8487	ENSG00000085840	Q13415	Origin recognition complex subunit 1	gencc,clinvar
ORC6	HGNC:17151	ENSG00000091651	Q9Y5N6	Origin recognition complex subunit 6	gencc
CDC45	HGNC:1739	ENSG00000093009	O75419	Cell division control protein 45 homolog	gencc
CDC6	HGNC:1744	ENSG00000094804	Q99741	Cell division control protein 6 homolog	gencc
GINS2	HGNC:24575	ENSG00000131153	Q9Y248	DNA replication complex GINS protein PSF2	gencc
GINS3	HGNC:25851	ENSG00000181938	Q9BRX5	DNA replication complex GINS protein PSF3	gencc
ORC4	HGNC:8490	ENSG00000115947	O43929	Origin recognition complex subunit 4	gencc
DONSON	HGNC:2993	ENSG00000159147	Q9NYP3	Protein downstream neighbor of Son	clinvar
MCM3	HGNC:6945	ENSG00000112118	P25205	DNA replication licensing factor MCM3	clinvar
MCM7	HGNC:6950	ENSG00000166508	P33993	DNA replication licensing factor MCM7	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC25A15	Mitochondrial ornithine transporter 1	Mitochondrial ornithine-citrulline antiporter.
GMNN	Geminin	Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC).
CDT1	DNA replication factor Cdt1	Required for both DNA replication and mitosis.
ORC1	Origin recognition complex subunit 1	Component of the origin recognition complex (ORC) that binds origins of replication.
ORC6	Origin recognition complex subunit 6	Component of the origin recognition complex (ORC) that binds origins of replication.
CDC45	Cell division control protein 45 homolog	Required for initiation of chromosomal DNA replication.
CDC6	Cell division control protein 6 homolog	Involved in the initiation of DNA replication.
GINS2	DNA replication complex GINS protein PSF2	Required for correct functioning of the GINS complex, a complex that plays an essential role in the initiation of DNA replication, and progression of DNA replication forks.
GINS3	DNA replication complex GINS protein PSF3	Required for correct functioning of the GINS complex, a complex that plays an essential role in the initiation of DNA replication, and progression of DNA replication forks.
ORC4	Origin recognition complex subunit 4	Component of the origin recognition complex (ORC) that binds origins of replication.
DONSON	Protein downstream neighbor of Son	Replisome component that maintains genome stability by protecting stalled or damaged replication forks.
MCM3	DNA replication licensing factor MCM3	Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for ‘once per cell cycle’ DNA replication initiation and elongation in eukaryotic cells.
MCM7	DNA replication licensing factor MCM7	Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for ‘once per cell cycle’ DNA replication initiation and elongation in eukaryotic cells.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 10 · Druggable fraction: 0.23

Family distribution

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

Family	Genes	Fold	FDR
Enzyme (other)	3	2.8×	0.103
Other/Unknown	10	1.4×	0.103

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC25A15	Other/Unknown	no		MCP_transmembrane, MCP_dom_sf, Mitochondrial_Carrier
GMNN	Other/Unknown	no		Geminin/Multicilin
CDT1	Other/Unknown	no		CDT1_Gemini-bd-like, Cdt1_C, WH_DNA-bd_sf
ORC1	Enzyme (other)	yes	3.6.4.B8	BAH_dom, AAA+_ATPase, ATPase_AAA_core
ORC6	Enzyme (other)	yes	3.6.4.B8	ORC6_cyclin_first, ORC6_met/pln, ORC6_cyclin-like_2nd
CDC45	Other/Unknown	no		CDC45
CDC6	Other/Unknown	no		AAA+_ATPase, Cdc6_C, Cdc6/18
GINS2	Other/Unknown	no		GINS_Psf2, GINS_A, GINS_bundle-like_dom_sf
GINS3	Other/Unknown	no		GINS_Psf3, GINS_A, GINS_bundle-like_dom_sf
ORC4	Enzyme (other)	yes	3.6.4.B8	AAA+_ATPase, ORC4, P-loop_NTPase
DONSON	Other/Unknown	no		Donson
MCM3	Other/Unknown	no		MCM_dom, AAA+_ATPase, Mcm3
MCM7	Other/Unknown	no		MCM_dom, AAA+_ATPase, MCM7

Expression context

Cohort genes with no expression data: 0.

13 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)	13
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	7
secondary oocyte	5
ventricular zone	5
embryo	3
ganglionic eminence	3
primordial germ cell in gonad	2
right testis	2
duodenum	1
liver	1
right lobe of liver	1
body of pancreas	1
mucosa of paranasal sinus	1
superficial temporal artery	1
male germ line stem cell (sensu Vertebrata) in testis	1
endothelial cell	1
cervix squamous epithelium	1
calcaneal tendon	1
cortical plate	1
left testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC25A15	198	ubiquitous	marker	liver, right lobe of liver, duodenum
GMNN	280	ubiquitous	marker	oocyte, body of pancreas, secondary oocyte
CDT1	185	ubiquitous	marker	mucosa of paranasal sinus, superficial temporal artery, oocyte
ORC1	152	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, ventricular zone, primordial germ cell in gonad
ORC6	249	ubiquitous	marker	oocyte, endothelial cell, secondary oocyte
CDC45	172	ubiquitous	marker	oocyte, secondary oocyte, right testis
CDC6	186	ubiquitous	marker	ventricular zone, ganglionic eminence, embryo
GINS2	206	ubiquitous	marker	oocyte, secondary oocyte, cervix squamous epithelium
GINS3	241	ubiquitous	marker	oocyte, secondary oocyte, primordial germ cell in gonad
ORC4	285	ubiquitous	marker	calcaneal tendon, oocyte, cortical plate
DONSON	247	ubiquitous	marker	ventricular zone, right testis, left testis
MCM3	283	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence
MCM7	143	ubiquitous	marker	embryo, ganglionic eminence, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 47.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MCM7	5,413
MCM3	3,953
CDC6	3,877
CDC45	3,357
ORC1	2,879
CDT1	2,813
GMNN	2,074
GINS2	1,627
ORC4	1,522
DONSON	1,477

Intra-cohort edges

A	B	Sources
CDC45	CDC6	string_interaction
CDC45	CDT1	string_interaction
CDC45	DONSON	intact
CDC45	GINS2	string_interaction
CDC45	GINS3	string_interaction
CDC45	GMNN	string_interaction
CDC45	MCM3	string_interaction
CDC45	MCM7	string_interaction
CDC45	ORC1	string_interaction
CDC45	ORC4	string_interaction
CDC45	ORC6	string_interaction
CDC6	CDT1	intact, string_interaction
CDC6	GINS3	string_interaction
CDC6	GMNN	string_interaction
CDC6	MCM3	string_interaction
CDC6	MCM7	string_interaction
CDC6	ORC1	string_interaction
CDC6	ORC4	string_interaction
CDC6	ORC6	string_interaction
CDT1	GINS2	string_interaction
CDT1	GINS3	string_interaction
CDT1	GMNN	biogrid_interaction, intact, string_interaction
CDT1	MCM3	string_interaction
CDT1	MCM7	string_interaction
CDT1	ORC1	string_interaction
CDT1	ORC4	string_interaction
CDT1	ORC6	intact, string_interaction
DONSON	GINS3	biogrid_interaction
DONSON	MCM7	biogrid_interaction
GINS2	GINS3	biogrid_interaction, intact, string_interaction
GINS2	MCM3	string_interaction
GINS2	MCM7	biogrid_interaction, intact
GINS3	MCM3	string_interaction
GINS3	MCM7	biogrid_interaction, string_interaction
GMNN	MCM3	string_interaction
GMNN	ORC4	string_interaction
GMNN	ORC6	string_interaction
MCM3	MCM7	biogrid_interaction, intact, string_interaction
MCM3	ORC1	string_interaction
MCM3	ORC4	string_interaction
MCM3	ORC6	string_interaction
MCM7	ORC1	string_interaction
MCM7	ORC4	string_interaction
MCM7	ORC6	string_interaction
ORC1	ORC4	biogrid_interaction, intact, string_interaction
ORC1	ORC6	string_interaction
ORC4	ORC6	biogrid_interaction, intact, string_interaction

Structural data

PDB: 11 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MCM3	P25205	28
MCM7	P33993	28
ORC4	O43929	15
ORC1	Q13415	14
GINS2	Q9Y248	10
GINS3	Q9BRX5	10
CDC45	O75419	7
CDC6	Q99741	7
GMNN	O75496	6
CDT1	Q9H211	6
ORC6	Q9Y5N6	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC25A15	Q9Y619	87.43
DONSON	Q9NYP3	72.94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 26. Enrichment computed across 13 evidence-associated genes (12 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 12 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Activation of the pre-replicative complex	9	244.7×	4e-20	GMNN, CDT1, ORC1, ORC6, CDC45, CDC6, MCM3, MCM7 (+1 more)
Activation of ATR in response to replication stress	7	175.3×	2e-14	ORC1, ORC6, CDC45, CDC6, MCM3, MCM7, ORC4
Assembly of the pre-replicative complex	8	92.8×	2e-14	GMNN, CDT1, ORC1, ORC6, CDC6, MCM3, MCM7, ORC4
Orc1 removal from chromatin	7	104.1×	6e-13	CDT1, ORC1, ORC6, CDC6, MCM3, MCM7, ORC4
Unwinding of DNA	5	366.0×	3e-12	CDC45, GINS2, GINS3, MCM3, MCM7
CDC6 association with the ORC:origin complex	4	475.8×	2e-10	ORC1, ORC6, CDC6, ORC4
DNA Replication Pre-Initiation	5	132.2×	7e-10	CDT1, CDC45, CDC6, MCM3, MCM7
Switching of origins to a post-replicative state	5	125.2×	7e-10	GMNN, CDT1, CDC6, MCM3, MCM7
Synthesis of DNA	5	125.2×	7e-10	CDT1, CDC45, CDC6, MCM3, MCM7
DNA Replication	5	99.1×	2e-09	CDT1, CDC45, CDC6, MCM3, MCM7
G1/S Transition	5	97.1×	2e-09	CDT1, CDC45, CDC6, MCM3, MCM7
Mitotic G1 phase and G1/S transition	5	76.8×	7e-09	CDT1, CDC45, CDC6, MCM3, MCM7
S Phase	5	75.5×	7e-09	CDT1, CDC45, CDC6, MCM3, MCM7
G1/S-Specific Transcription	4	119.0×	5e-08	CDT1, ORC1, CDC45, CDC6
E2F-enabled inhibition of pre-replication complex formation	3	317.2×	1e-07	ORC1, ORC6, ORC4
DNA strand elongation	3	285.5×	2e-07	CDC45, MCM3, MCM7
G2/M Checkpoints	4	44.8×	2e-06	CDC45, CDC6, MCM3, MCM7
Cell Cycle, Mitotic	5	20.1×	4e-06	CDT1, CDC45, CDC6, MCM3, MCM7
Cell Cycle Checkpoints	4	29.5×	1e-05	CDC45, CDC6, MCM3, MCM7
Cell Cycle	5	15.0×	1e-05	CDT1, CDC45, CDC6, MCM3, MCM7
Assembly of the ORC complex at the origin of replication	3	41.4×	6e-05	ORC1, ORC6, ORC4
SLC25A15 variants cause hyperornithinemia-hyperammonemia-homocitrullinemia syndrome	1	475.8×	0.002	SLC25A15
Urea cycle	1	73.2×	0.015	SLC25A15
Transcription of E2F targets under negative control by DREAM complex	1	45.3×	0.024	CDC6
G0 and Early G1	1	36.6×	0.028	CDC6
CDK-mediated phosphorylation and removal of Cdc6	1	14.2×	0.068	CDC6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
DNA replication initiation	7	336.1×	1e-15	ORC1, ORC6, CDC45, CDC6, MCM3, MCM7, ORC4
DNA replication	6	76.2×	2e-09	CDC45, GINS2, GINS3, DONSON, MCM3, MCM7
double-strand break repair via break-induced replication	4	398.9×	3e-09	CDC45, GINS2, MCM3, MCM7
regulation of DNA-templated DNA replication initiation	4	324.1×	5e-09	GMNN, CDT1, MCM3, MCM7
mitotic DNA replication checkpoint signaling	3	353.5×	6e-07	ORC1, CDC6, DONSON
DNA replication checkpoint signaling	3	299.1×	9e-07	CDT1, CDC45, CDC6
negative regulation of DNA-templated DNA replication	2	864.2×	1e-05	GMNN, CDT1
mitotic DNA replication initiation	2	432.1×	5e-05	CDT1, MCM3
DNA strand elongation involved in DNA replication	2	288.1×	1e-04	MCM3, MCM7
negative regulation of DNA replication	2	136.4×	5e-04	GMNN, CDC6
DNA replication preinitiation complex assembly	1	1296.3×	0.003	CDT1
mitotic DNA replication preinitiation complex assembly	1	1296.3×	0.003	CDC45
mitotic pre-replicative complex assembly	1	1296.3×	0.003	CDT1
negative regulation of cell cycle	2	44.7×	0.003	GMNN, CDT1
response to sorbitol	1	648.1×	0.005	CDT1
negative regulation of mitotic DNA replication initiation	1	648.1×	0.005	GMNN
nuclear DNA replication	1	432.1×	0.007	DONSON
traversing start control point of mitotic cell cycle	1	324.1×	0.008	CDC6
mitochondrial L-ornithine transmembrane transport	1	324.1×	0.008	SLC25A15
regulation of nuclear cell cycle DNA replication	1	259.3×	0.010	CDT1
polar body extrusion after meiotic divisions	1	259.3×	0.010	ORC4
regulation of phosphorylation	1	216.1×	0.010	MCM7
L-lysine transmembrane transport	1	216.1×	0.010	SLC25A15
cellular response to vasopressin	1	162.0×	0.013	CDC6
L-arginine transmembrane transport	1	108.0×	0.019	SLC25A15
urea cycle	1	99.7×	0.019	SLC25A15
positive regulation of chromosome segregation	1	99.7×	0.019	CDC6
attachment of mitotic spindle microtubules to kinetochore	1	81.0×	0.023	CDT1
protein polymerization	1	76.2×	0.023	ORC4
cellular response to angiotensin	1	72.0×	0.024	CDC6

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 11

Druggability breadth: 5 of 13 evidence-associated genes (38%) 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
GMNN	CLOTRIMAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GMNN	82	4
CDC45	1	2
SLC25A15	0	0
CDT1	0	0
ORC1	0	0
ORC6	0	0
CDC6	0	0
GINS2	0	0
GINS3	0	0
ORC4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CLOTRIMAZOLE	4	GMNN
COLCHICINE	4	GMNN
SALMETEROL XINAFOATE	4	GMNN
AMIODARONE HYDROCHLORIDE	4	GMNN
RALOXIFENE HYDROCHLORIDE	4	GMNN
IDARUBICIN	4	GMNN
NICARDIPINE HYDROCHLORIDE	4	GMNN
DOBUTAMINE HYDROCHLORIDE	4	GMNN
GUANFACINE HYDROCHLORIDE	4	GMNN
BROMOCRIPTINE MESYLATE	4	GMNN
DIHYDROERGOTAMINE MESYLATE	4	GMNN
DOXAZOSIN MESYLATE	4	GMNN
PROMETHAZINE HYDROCHLORIDE	4	GMNN
THIORIDAZINE HYDROCHLORIDE	4	GMNN
FLUOXETINE HYDROCHLORIDE	4	GMNN
TRIFLUPROMAZINE HYDROCHLORIDE	4	GMNN
DEQUALINIUM CHLORIDE	4	GMNN
TETRACAINE HYDROCHLORIDE	4	GMNN
MIFEPRISTONE	4	GMNN
PROCHLORPERAZINE MALEATE	4	GMNN
MITOXANTRONE HYDROCHLORIDE	4	GMNN
PIMOZIDE	4	GMNN
NICLOSAMIDE	4	GMNN
FLUPHENAZINE HYDROCHLORIDE	4	GMNN
FELODIPINE	4	GMNN
AZACITIDINE	4	GMNN
EPHEDRINE SULFATE	4	GMNN
PIRENZEPINE HYDROCHLORIDE	4	GMNN
MIBEFRADIL DIHYDROCHLORIDE	4	GMNN
AZATHIOPRINE	4	GMNN

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
MCM3	10	Binding:10
MCM7	9	Binding:9
GMNN	8	Functional:8
CDC45	8	Binding:8
CDC6	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ORC1	3.6.4.B8
ORC6	3.6.4.B8
ORC4	3.6.4.B8

Pharmacogenomics

Cohort genes with a PharmGKB record: 13; 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)
CLOTRIMAZOLE	4	GMNN
COLCHICINE	4	GMNN
SALMETEROL XINAFOATE	4	GMNN
AMIODARONE HYDROCHLORIDE	4	GMNN
RALOXIFENE HYDROCHLORIDE	4	GMNN
IDARUBICIN	4	GMNN
NICARDIPINE HYDROCHLORIDE	4	GMNN
DOBUTAMINE HYDROCHLORIDE	4	GMNN
GUANFACINE HYDROCHLORIDE	4	GMNN
BROMOCRIPTINE MESYLATE	4	GMNN
DIHYDROERGOTAMINE MESYLATE	4	GMNN
DOXAZOSIN MESYLATE	4	GMNN
PROMETHAZINE HYDROCHLORIDE	4	GMNN
THIORIDAZINE HYDROCHLORIDE	4	GMNN
FLUOXETINE HYDROCHLORIDE	4	GMNN
TRIFLUPROMAZINE HYDROCHLORIDE	4	GMNN
DEQUALINIUM CHLORIDE	4	GMNN
TETRACAINE HYDROCHLORIDE	4	GMNN
MIFEPRISTONE	4	GMNN
PROCHLORPERAZINE MALEATE	4	GMNN
MITOXANTRONE HYDROCHLORIDE	4	GMNN
PIMOZIDE	4	GMNN
NICLOSAMIDE	4	GMNN
FLUPHENAZINE HYDROCHLORIDE	4	GMNN
FELODIPINE	4	GMNN
AZACITIDINE	4	GMNN
EPHEDRINE SULFATE	4	GMNN
PIRENZEPINE HYDROCHLORIDE	4	GMNN
MIBEFRADIL DIHYDROCHLORIDE	4	GMNN
AZATHIOPRINE	4	GMNN

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GMNN
B	Phased (≥1) drug, not yet approved	1	CDC45
C	Druggable family + PDB, no drug	3	ORC1, ORC6, ORC4
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	8	SLC25A15, CDT1, CDC6, GINS2, GINS3, DONSON, MCM3, MCM7

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CDT1	0	GMNN
CDC6	1	CDC45
GINS2	0	CDC45
GINS3	0	CDC45
SLC25A15	0	—
ORC1	0	—
ORC6	0	—
ORC4	0	—
DONSON	0	—
MCM3	10	—
MCM7	9	—

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
NCT04569149	Not specified	RECRUITING	Primordial Dwarfism Registry