Orofaciodigital syndrome type 14

Summary

Orofaciodigital syndrome type 14 (MONDO:0014413) is a disease caused by C2CD3 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: C2CD3 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 50
• Phenotypes (HPO): 42

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

42 HPO clinical features (Orphanet curated; top 42 by frequency):

HPO ID	Term	Frequency
HP:0000039	Epispadias	Frequent (30-79%)
HP:0000175	Cleft palate	Frequent (30-79%)
HP:0000180	Lobulated tongue	Frequent (30-79%)
HP:0000191	Accessory oral frenulum	Frequent (30-79%)
HP:0000243	Trigonocephaly	Frequent (30-79%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000308	Microretrognathia	Frequent (30-79%)
HP:0000340	Sloping forehead	Frequent (30-79%)
HP:0000358	Posteriorly rotated ears	Frequent (30-79%)
HP:0000414	Bulbous nose	Frequent (30-79%)
HP:0000465	Webbed neck	Frequent (30-79%)
HP:0000470	Short neck	Frequent (30-79%)
HP:0000480	Retinal coloboma	Frequent (30-79%)
HP:0000506	Telecanthus	Frequent (30-79%)
HP:0000582	Upslanted palpebral fissure	Frequent (30-79%)
HP:0001162	Postaxial hand polydactyly	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001305	Dandy-Walker malformation	Frequent (30-79%)
HP:0001338	Partial agenesis of the corpus callosum	Frequent (30-79%)
HP:0001629	Ventricular septal defect	Frequent (30-79%)
HP:0001643	Patent ductus arteriosus	Frequent (30-79%)
HP:0001830	Postaxial foot polydactyly	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0002079	Hypoplasia of the corpus callosum	Frequent (30-79%)
HP:0002198	Dilated fourth ventricle	Frequent (30-79%)
HP:0002419	Molar tooth sign on MRI	Frequent (30-79%)
HP:0007082	Dilated third ventricle	Frequent (30-79%)
HP:0007165	Periventricular heterotopia	Frequent (30-79%)
HP:0008689	Bilateral cryptorchidism	Frequent (30-79%)
HP:0008753	Aplasia of the epiglottis	Frequent (30-79%)
HP:0010051	Deviation of the hallux	Frequent (30-79%)
HP:0010055	Broad hallux	Frequent (30-79%)
HP:0010066	Duplication of phalanx of hallux	Frequent (30-79%)
HP:0010297	Bifid tongue	Frequent (30-79%)
HP:0010535	Sleep apnea	Frequent (30-79%)
HP:0011069	Supernumerary tooth	Frequent (30-79%)
HP:0011471	Gastrostomy tube feeding in infancy	Frequent (30-79%)
HP:0011802	Hamartoma of tongue	Frequent (30-79%)
HP:0012447	Abnormal myelination	Frequent (30-79%)
HP:0100954	Open operculum	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	orofaciodigital syndrome type 14
Mondo ID	MONDO:0014413
OMIM	615948
Orphanet	434179
DOID	DOID:0060958
SNOMED CT	763837007
UMLS	C4706604
MedGen	1635470
GARD	0013655
Is cancer (heuristic)	no

Also known as: C2CD3 orofaciodigital syndrome · microcephaly-cerebral malformation-orofaciodigital syndrome · OFD14 · oral-facial-digital syndrome type 14 · orofaciodigital syndrome caused by mutation in C2CD3 · orofaciodigital syndrome type 14 · orofaciodigital syndrome XIV

Data availability: 50 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › multiple congenital anomalies/dysmorphic syndrome › multiple congenital anomalies/dysmorphic syndrome-intellectual disability › orofaciodigital syndrome type 14

Related subtypes (337): Neu-Laxova syndrome, acrofacial dysostosis, Catania type, aortic arch anomaly-facial dysmorphism-intellectual disability syndrome, blepharonasofacial malformation syndrome, brachydactyly-nystagmus-cerebellar ataxia syndrome, craniofaciofrontodigital syndrome, uveal coloboma-cleft lip and palate-intellectual disability, Ramos-Arroyo syndrome, extrasystoles-short stature-hyperpigmentation-microcephaly syndrome, Floating-Harbor syndrome, Myhre syndrome, hirsutism-skeletal dysplasia-intellectual disability syndrome, Johnson neuroectodermal syndrome, KBG syndrome, trichorhinophalangeal syndrome type II, Lenz-Majewski hyperostotic dwarfism, Bannayan-Riley-Ruvalcaba syndrome, microcephaly-deafness-intellectual disability syndrome, ophthalmoplegia-intellectual disability-lingua scrotalis syndrome, omphalocele syndrome, Shprintzen-Goldberg type, Shprintzen-Goldberg syndrome, Smith-Magenis syndrome, delayed speech-facial asymmetry-strabismus-ear lobe creases syndrome, holoprosencephaly-radial heart renal anomalies syndrome, Wolf-Hirschhorn syndrome, pseudoprogeria syndrome, acrocallosal syndrome, acrofacial dysostosis Rodriguez type, agnathia-otocephaly complex, Stimmler syndrome, anencephaly 1, aniridia-renal agenesis-psychomotor retardation syndrome, Biemond syndrome type 2, bird headed-dwarfism, Montreal type, Bowen-Conradi syndrome, Elsahy-Waters syndrome, C syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, Cohen syndrome, cortical blindness-intellectual disability-polydactyly syndrome, Costello syndrome, temtamy syndrome, cardiocranial syndrome, Pfeiffer type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, Dubowitz syndrome, Bonnemann-Meinecke-Reich syndrome, epilepsy-telangiectasia syndrome, faciocardiorenal syndrome, fountain syndrome, Fryns syndrome, GAPO syndrome, Hall-Riggs syndrome, Mowat-Wilson syndrome, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, hypospadias-intellectual disability, Goldblatt type syndrome, Stromme syndrome, Johanson-Blizzard syndrome, Kapur-Toriello syndrome, oculocerebrofacial syndrome, Kaufman type, Keutel syndrome, Lambert syndrome, Laurence-Moon syndrome, intellectual disability-spasticity-ectrodactyly syndrome, prominent glabella-microcephaly-hypogenitalism syndrome, Marden-Walker syndrome, microcephaly-glomerulonephritis-marfanoid habitus syndrome, marfanoid habitus-autosomal recessive intellectual disability syndrome, McDonough syndrome, intellectual disability-dysmorphism-hypogonadism-diabetes mellitus syndrome, intellectual disability, Buenos-Aires type, microcephaly-cardiomyopathy syndrome, Say-Barber-Miller syndrome, microcephaly-cervical spine fusion anomalies syndrome, Jawad syndrome, lethal multiple pterygium syndrome, neurofaciodigitorenal syndrome, oculo-palato-cerebral syndrome, Oliver syndrome, lethal omphalocele-cleft palate syndrome, Peters plus syndrome, Pfeiffer-Palm-Teller syndrome, urban-Rogers-Meyer syndrome, Wiedemann-Rautenstrauch syndrome, holoprosencephaly-postaxial polydactyly syndrome, radioulnar synostosis-developmental delay-hypotonia syndrome, Ulbright-Hodes syndrome, microbrachycephaly-ptosis-cleft lip syndrome, Smith-Lemli-Opitz syndrome, congenital heart defect-round face-developmental delay syndrome, Filippi syndrome, upper limb defect-eye and ear abnormalities syndrome, Weaver syndrome, intellectual disability, Wolff type, CHIME syndrome, X-linked intellectual disability-plagiocephaly syndrome, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, creatine transporter deficiency, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, chromosome Xp11.23-p11.22 duplication syndrome, X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome, SSR4-congenital disorder of glycosylation, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, intellectual disability-balding-patella luxation-acromicria syndrome, syndromic X-linked intellectual disability 5, male hypergonadotropic hypogonadism-intellectual disability-skeletal anomalies syndrome, X-linked intellectual disability with marfanoid habitus, N syndrome, pterygium colli-intellectual disability-digital anomalies syndrome, Lowry-MacLean syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, pseudoaminopterin syndrome, acrocardiofacial syndrome, Ayme-Gripp syndrome, Harrod syndrome, fallot complex-intellectual disability-growth delay syndrome, MMEP syndrome, epilepsy-microcephaly-skeletal dysplasia syndrome, Fine-Lubinsky syndrome, intellectual disability-sparse hair-brachydactyly syndrome, colobomatous microphthalmia - obesity - hypogenitalism - intellectual disability syndrome, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, Wiedemann-Steiner syndrome, cerebrooculonasal syndrome, genitopatellar syndrome, intellectual disability-obesity-prognathism-eye and skin anomalies syndrome, intellectual disability-brachydactyly-Pierre Robin syndrome, AICA-ribosiduria, Goldberg-Shprintzen syndrome, complex cortical dysplasia with other brain malformations 7, Kleefstra syndrome, Koolen-de Vries syndrome, agammaglobulinemia-microcephaly-craniosynostosis-severe dermatitis syndrome, mandibulofacial dysostosis-microcephaly syndrome, camptodactyly syndrome, Guadalajara type 3, chromosome 15q13.3 microdeletion syndrome, chromosome 6pter-p24 deletion syndrome, Zechi-Ceide syndrome, chromosome 19q13.11 deletion syndrome, chromosome 5p13 duplication syndrome, chromosome 17p13.3 duplication syndrome, syndromic multisystem autoimmune disease due to ITCH deficiency, chromosome 15q24 deletion syndrome, chromosome 17q21.31 duplication syndrome, chromosome 19p13.13 deletion syndrome, THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome, DYRK1A-related intellectual disability syndrome, chromosome 8q21.11 deletion syndrome, microcephaly-cerebellar hypoplasia-cardiac conduction defect syndrome, chromosome 16q22 deletion syndrome, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, short ulna-dysmorphism-hypotonia-intellectual disability syndrome, microcephaly-intellectual disability-phalangeal and neurological anomalies syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, Hartsfield-Bixler-Demyer syndrome, developmental and epileptic encephalopathy, 18, severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome, CTCF-related neurodevelopmental disorder, severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome, 8q24.3 microdeletion syndrome, microcephaly-thin corpus callosum-intellectual disability syndrome, macrocephaly-developmental delay syndrome, chromosome 5q12 deletion syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, autism spectrum disorder due to AUTS2 deficiency, developmental and epileptic encephalopathy, 23, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, Tatton-Brown-Rahman overgrowth syndrome, Catel-Manzke syndrome, cerebellar-facial-dental syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, autosomal recessive spinocerebellar ataxia 20, Houge-Janssens syndrome 1, Houge-Janssens syndrome 2, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome, hypomyelinating leukodystrophy 10, congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome, palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, spastic paraplegia-severe developmental delay-epilepsy syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, TELO2-related intellectual disability-neurodevelopmental disorder, transketolase deficiency, severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, tall stature-intellectual disability-renal anomalies syndrome, ZTTK syndrome, short stature-brachydactyly-obesity-global developmental delay syndrome, mucopolysaccharidosis-plus syndrome, hypotonia, ataxia, and delayed development syndrome, caudal appendage-deafness syndrome, arachnodactyly-abnormal ossification-intellectual disability syndrome, ataxia-photosensitivity-short stature syndrome, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, brachydactyly-mesomelia-intellectual disability-heart defects syndrome, cardiofaciocutaneous syndrome, cataract-intellectual disability-anal atresia-urinary defects syndrome, cataract-deafness-hypogonadism syndrome, Coffin-Siris syndrome, intellectual disability-hypoplastic corpus callosum-preauricular tag syndrome, craniodigital syndrome-intellectual disability syndrome, cryptorchidism-arachnodactyly-intellectual disability syndrome, facial dysmorphism-shawl scrotum-joint laxity syndrome, epiphyseal dysplasia-hearing loss-dysmorphism syndrome, Cornelia de Lange syndrome, cleft palate-short stature-vertebral anomalies syndrome, Hennekam syndrome, Hernández-Aguirre Negrete syndrome, holoprosencephaly, dysmorphism-short stature-deafness-disorder of sex development syndrome, 5q14.3 microdeletion syndrome, Kabuki syndrome, ptosis-syndactyly-learning difficulties syndrome, macrocephaly-short stature-paraplegia syndrome, Warburg micro syndrome, microcephaly-seizures-intellectual disability-heart disease syndrome, microcephaly-cleft palate syndrome, microcephaly-microcornea syndrome, Seemanova type, multiple congenital anomalies due to 14q32.2 maternally expressed gene defect, neuroectodermal-endocrine syndrome, Opitz G/BBB syndrome, Xp22.13p22.2 duplication syndrome, short stature-webbed neck-heart disease syndrome, microtriplication 11q24.1, preaxial polydactyly-colobomata-intellectual disability syndrome, blepharophimosis - intellectual disability syndrome, 3MC syndrome, Baraitser-Winter cerebrofrontofacial syndrome, 11p15.4 microduplication syndrome, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, intellectual disability-short stature-hypertelorism syndrome, intellectual disability-polydactyly-uncombable hair syndrome, 20p13 microdeletion syndrome, 7p22.1 microduplication syndrome, intellectual disability-hypotonia-brachycephaly-pyloric stenosis-cryptorchidism syndrome, 15q overgrowth syndrome, van Maldergem syndrome, distal 17p13.1 microdeletion syndrome, deafness-genital anomalies-metacarpal and metatarsal synostosis syndrome, muscular hypertrophy-hepatomegaly-polyhydramnios syndrome, aphonia-deafness-retinal dystrophy-bifid halluces-intellectual disability syndrome, spondylocostal dysostosis-hypospadias-intellectual disability syndrome, telecanthus-hypertelorism-strabismus-pes cavus syndrome, microcephaly-brachydactyly-kyphoscoliosis syndrome, Weaver-Williams syndrome, 20q11.2 microduplication syndrome, 2p13.2 microdeletion syndrome, intellectual disability-seizures-macrocephaly-obesity syndrome, intellectual disability-facial dysmorphism-hand anomalies syndrome, XYLT1-congenital disorder of glycosylation, 3q27.3 microdeletion syndrome, 9q31.1q31.3 microdeletion syndrome, 14q24.1q24.3 microdeletion syndrome, FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome, 13q12.3 microdeletion syndrome, cono-spondylar dysplasia, microcephaly-short stature-intellectual disability-facial dysmorphism syndrome, severe intellectual disability-hypotonia-strabismus-coarse face-planovalgus syndrome, 11q22.2q22.3 microdeletion syndrome, 20q11.2 microdeletion syndrome, 19p13.3 microduplication syndrome, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, 1p35.2 microdeletion syndrome, megalencephaly-severe kyphoscoliosis-overgrowth syndrome, intellectual disability-muscle weakness-short stature-facial dysmorphism syndrome, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, corpus callosum agenesis-macrocephaly-hypertelorism syndrome, DeSanto-Shinawi syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, Ritscher-Schinzel syndrome, visceral neuropathy-brain anomalies-facial dysmorphism-developmental delay syndrome, brain malformation-congenital heart disease-postaxial polydactyly syndrome, Rubinstein-Taybi syndrome, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, osteopenia-myopia-hearing loss-intellectual disability-facial dysmorphism syndrome, severe intellectual disability-epilepsy-anal anomalies-distal phalangeal hypoplasia, intellectual disability, autosomal dominant 47, intellectual disability, autosomal dominant 48, skeletal dysplasia-T-cell immunodeficiency-developmental delay syndrome, congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome, developmental and epileptic encephalopathy, 73, pancreatic agenesis-holoprosencephaly syndrome, oculocerebrodental syndrome, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, KAT6B-related multiple congenital anomalies syndrome, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 16p12.1p12.3 triplication syndrome, 9q33.3q34.11 microdeletion syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, Gabriele de Vries syndrome, Skraban-Deardorff syndrome, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, Pilarowski-Bjornsson syndrome, glycosylphosphatidylinositol biosynthesis defect 15, multiple congenital anomalies-hypotonia-seizures syndrome, mesomelic dysplasia-digital anomalies-intellectual disability syndrome, KDM3B-related intellectual disability-facial dysmorphism-short stature syndrome, SLC12A2-related developmental delay-intellectual disability-sensorineural deafness syndrome, intellectual disability-early-onset cataract-microcephaly syndrome, cleft palate-congenital heart defect-intellectual disability syndrome, PRC-2 complex-related overgrowth spectrum, orofacial clefting-cardiac anomalies-facial dysmorphism syndrome, severe congenital myelofibrosis-pancytopenia-intellectual disability-neurologic and ophthalmic abnormalities syndrome, progressive hypotonia-intellectual disability-facial dysmorphism syndrome due to FYVE-defective RBSN, intellectual disability-epilepsy-dental anomalies-facial dysmorphism syndrome, 2q13 microdeletion syndrome, 10p13-p14 deletion syndrome, 3q26q28 deletion syndrome, Pitt-Hopkins or Pitt-Hopkins-like syndrome, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, Martsolf syndrome 1

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

50 retrieved; paginated sample, class counts are floors:

19 uncertain significance, 9 conflicting classifications of pathogenicity, 9 likely pathogenic, 6 pathogenic/likely pathogenic, 4 pathogenic, 2 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1072108	NM_001286577.2(C2CD3):c.994dup (p.Val332fs)	C2CD3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075627	NM_001286577.2(C2CD3):c.1861C>T (p.Arg621Ter)	C2CD3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
144038	NM_001286577.2(C2CD3):c.184C>T (p.Arg62Ter)	C2CD3	Pathogenic	criteria provided, single submitter
144039	NM_001286577.2(C2CD3):c.3085T>G (p.Cys1029Gly)	C2CD3	Pathogenic	no assertion criteria provided
144040	NM_001286577.2(C2CD3):c.3911-2A>T	C2CD3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454274	NM_001286577.2(C2CD3):c.2706_2710dup (p.His904fs)	C2CD3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1878236	NM_001286577.2(C2CD3):c.2969_2972delinsGGTTTACA (p.Ser990fs)	C2CD3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3014634	NM_001286577.2(C2CD3):c.1996C>T (p.Arg666Ter)	C2CD3	Pathogenic	criteria provided, multiple submitters, no conflicts
3668386	NM_001286577.2(C2CD3):c.2733_2740delAGATGCTA (p.Ala913fs)	C2CD3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
625150	NM_001286577.2(C2CD3):c.5090+5G>C	C2CD3	Pathogenic	no assertion criteria provided
1323994	NM_001286577.2(C2CD3):c.1962+2T>A	C2CD3	Likely pathogenic	criteria provided, single submitter
2504061	NM_001286577.2(C2CD3):c.3345-1G>A	C2CD3	Likely pathogenic	criteria provided, single submitter
2585641	NM_001286577.2(C2CD3):c.1730G>A (p.Arg577His)	C2CD3	Likely pathogenic	no assertion criteria provided
2585642	NM_001286577.2(C2CD3):c.2720A>G (p.Tyr907Cys)	C2CD3	Likely pathogenic	no assertion criteria provided
3069105	NM_001286577.2(C2CD3):c.2_9del (p.Met1fs)	C2CD3	Likely pathogenic	criteria provided, single submitter
3234896	NM_001286577.2(C2CD3):c.5600dup (p.Cys1867fs)	C2CD3	Likely pathogenic	criteria provided, single submitter
418736	NM_001286577.2(C2CD3):c.708-2_708-1del	C2CD3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4687824	NM_001286577.2(C2CD3):c.1088+2T>C	C2CD3	Likely pathogenic	criteria provided, single submitter
625149	NM_001286577.2(C2CD3):c.1365+1G>A	C2CD3	Likely pathogenic	criteria provided, single submitter
1033366	NM_001286577.2(C2CD3):c.3650C>G (p.Ala1217Gly)	C2CD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1213728	NM_001286577.2(C2CD3):c.6001del (p.Cys2001fs)	C2CD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1366316	NM_001286577.2(C2CD3):c.5728C>G (p.Pro1910Ala)	C2CD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1366317	NM_001286577.2(C2CD3):c.5726T>C (p.Leu1909Pro)	C2CD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2598302	NM_001286577.2(C2CD3):c.1160C>G (p.Thr387Arg)	C2CD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2901729	NM_001286577.2(C2CD3):c.7027C>T (p.Arg2343Trp)	C2CD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
548589	NM_001286577.2(C2CD3):c.6968G>A (p.Arg2323His)	C2CD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
715514	NM_001286577.2(C2CD3):c.3741G>C (p.Gln1247His)	C2CD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
828028	NM_001286577.2(C2CD3):c.5929C>T (p.Arg1977Ter)	C2CD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030511	NM_001286577.2(C2CD3):c.2704C>A (p.Pro902Thr)	C2CD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1194018	NM_001286577.2(C2CD3):c.5882-332A>G	C2CD3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
C2CD3	Definitive	Autosomal recessive	orofaciodigital syndrome type 14	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
C2CD3	Orphanet:434179	Orofaciodigital syndrome type 14

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
C2CD3	HGNC:24564	ENSG00000168014	Q4AC94	C2 domain-containing protein 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
C2CD3	C2 domain-containing protein 3	Component of the centrioles that acts as a positive regulator of centriole elongation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

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

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
C2CD3	Other/Unknown	no		C2_dom, C2_domain_sf, C2_C2CD3

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
right uterine tube	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
C2CD3	282	ubiquitous	marker	sural nerve, right uterine tube, bronchial epithelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C2CD3	819

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C2CD3	Q4AC94	55.65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Anchoring of the basal body to the plasma membrane	1	113.1×	0.014	C2CD3
Cilium Assembly	1	108.8×	0.014	C2CD3
Organelle biogenesis and maintenance	1	66.0×	0.015	C2CD3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
neural plate axis specification	1	8426.0×	0.002	C2CD3
centriole elongation	1	4213.0×	0.002	C2CD3
regulation of proteolysis	1	1296.3×	0.003	C2CD3
protein localization to centrosome	1	674.1×	0.004	C2CD3
regulation of smoothened signaling pathway	1	624.1×	0.004	C2CD3
neural tube development	1	526.6×	0.004	C2CD3
embryonic digit morphogenesis	1	300.9×	0.005	C2CD3
non-motile cilium assembly	1	290.6×	0.005	C2CD3
heart looping	1	267.5×	0.005	C2CD3
protein processing	1	170.2×	0.008	C2CD3
brain development	1	79.5×	0.014	C2CD3
cilium assembly	1	73.6×	0.014	C2CD3
in utero embryonic development	1	72.0×	0.014	C2CD3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
C2CD3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	C2CD3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
C2CD3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.