C2CD3 (C2 domain containing 3 centriole elongation regulator)

Gene

• Entrez ID: 26005
• Gene name: C2 domain containing 3 centriole elongation regulator
• Gene symbol: C2CD3
• Synonyms (NCBI Gene): OFD14
• Chromosome: 11
• Chromosome location: 11q13.4
• Summary: This gene encodes a protein that functions as a regulator of centriole elongation. Studies of the orthologous mouse protein show that it promotes centriolar distal appendage assembly and is also required for the recruitment of other ciliogenic proteins, i

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs78878933	T>C,G	Conflicting-interpretations-of-pathogenicity	Missense variant, non coding transcript variant, coding sequence variant
rs149366137	T>A	Pathogenic	Splice acceptor variant
rs150291837	C>T	Uncertain-significance, pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant, non coding transcript variant, downstream transcript variant
rs555646012	G>T	Conflicting-interpretations-of-pathogenicity	Genic upstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs587777653	G>A	Pathogenic	Genic upstream transcript variant, 5 prime UTR variant, coding sequence variant, non coding transcript variant, stop gained
rs587777654	A>C,T	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs769076549	CT>-	Pathogenic	Splice acceptor variant, genic upstream transcript variant
rs774746175	A>C,G	Likely-pathogenic	Genic upstream transcript variant, coding sequence variant, non coding transcript variant, missense variant, 5 prime UTR variant
rs863225151	C>A	Pathogenic	Splice donor variant
rs1064793399	C>A	Uncertain-significance, likely-pathogenic	Non coding transcript variant, 3 prime UTR variant, coding sequence variant, missense variant
rs1064793941	C>T	Pathogenic	Splice donor variant
rs1174615027	C>T	Pathogenic	Intron variant, genic upstream transcript variant, splice donor variant
rs1565237232	C>G	Pathogenic	Intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019082	hsa-miR-335-5p	Microarray	18185580

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001701	Process	In utero embryonic development	IEA
GO:0001947	Process	Heart looping	IEA
GO:0005515	Function	Protein binding	IPI	24997988, 26496610
GO:0005737	Component	Cytoplasm	IEA
GO:0005813	Component	Centrosome	IDA	21399614
GO:0005814	Component	Centriole	IBA
GO:0005814	Component	Centriole	IDA	23769972
GO:0005814	Component	Centriole	IEA
GO:0005815	Component	Microtubule organizing center	IBA
GO:0005829	Component	Cytosol	TAS
GO:0005856	Component	Cytoskeleton	IEA
GO:0007389	Process	Pattern specification process	IEA
GO:0007420	Process	Brain development	IEA
GO:0008589	Process	Regulation of smoothened signaling pathway	IEA
GO:0016485	Process	Protein processing	IEA
GO:0021915	Process	Neural tube development	IEA
GO:0021997	Process	Neural plate axis specification	IEA
GO:0030030	Process	Cell projection organization	IEA
GO:0030162	Process	Regulation of proteolysis	IEA
GO:0030326	Process	Embryonic limb morphogenesis	IEA
GO:0034451	Component	Centriolar satellite	IBA
GO:0034451	Component	Centriolar satellite	IDA	24997988
GO:0034451	Component	Centriolar satellite	IEA
GO:0036064	Component	Ciliary basal body	IEA
GO:0042733	Process	Embryonic digit morphogenesis	IEA
GO:0042995	Component	Cell projection	IEA
GO:0060271	Process	Cilium assembly	IBA
GO:0060271	Process	Cilium assembly	IEA
GO:0060271	Process	Cilium assembly	IEA
GO:0061511	Process	Centriole elongation	IBA
GO:0061511	Process	Centriole elongation	IDA	24997988
GO:0061511	Process	Centriole elongation	IEA
GO:0071539	Process	Protein localization to centrosome	IBA
GO:0071539	Process	Protein localization to centrosome	IDA	24997988
GO:0071539	Process	Protein localization to centrosome	IEA
GO:0071539	Process	Protein localization to centrosome	IEA
GO:1905515	Process	Non-motile cilium assembly	IMP	23769972

Other IDs

• MIM: 615944
• HGNC: 24564
• e!Ensembl: ENSG00000168014

Protein

• UniProt ID: Q4AC94
• Protein name: C2 domain-containing protein 3
• Protein function: Component of the centrioles that acts as a positive regulator of centriole elongation (PubMed:24997988). Promotes assembly of centriolar distal appendage, a structure at the distal end of the mother centriole that acts as an anchor of the cilium
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00168	C2	789 → 918	C2 domain	Domain
  PF00168	C2	1197 → 1341	C2 domain	Domain
  PF00168	C2	1636 → 1747	C2 domain	Domain

• Sequence:

  MKQRKGQGSGGSRGRKKRGLSDISPSTSLPPLVEGQLRCFLKLTVNRVIWKIAKPPTCVL
  VRVRWWGETSDGTLFCPRDALQTEPKAVRTTTRYAIRCGPKQFTSYLTDMAVLVLEVITK
  LDGLPIGRVQINGLAQLSPTHQINGFFTIVSSTSKKLGELQVSLALEPLSETYDSYHPLP
  TTDMTENVLLSKQGFRENTEPSSTQFQVPSRPRDIHTIKIDGKELAANSSRSTTPRGKDH
  VCFAENPDTIKDSSFGLQHSLNSGQSLESVTLKGRAPRKQMSLLNSSEFQPQIRTVAKSH
  SDSCILSSNNLPTKDLLSALLEQGNKLRNAMVISAMKSSPETSMLLDQVHPPINEDSLRA
  STQIRAFSRNRFKDHIEDHLLPSTENTFWRHDTKADTRAIQLLLGSAELSQGNFWDGLGS
  PPDSPSPGSDVYCISELNDPQYDQSLLENLFYTAPKSDTSISDFLSEEDDIVPSKKISQS
  TALARSSKVLESSDHKLKKRSAGKRNRNLVEQQMLSETPEDAQTMTLSVDRLALLGRTHS
  VRIIIETMGVPPDSPQMTPGKKSYAGPPPKVTTAKKRTFFVEYHFPVGFSESGLGKTALI
  TEVVRLASSKITDGKVKFQQRFVFPVQFGGPMIEHWWNSNLTFQIYVKKTPQKKPEVIGS
  VSLSLRAVIQSELLSFSDQLPVQQENGQSPFGPLKVTMELITDNKDFTGINTKLSGNTHY
  TPLCAPTSPNKALPELNQDMTCTKNPQNLNQIHEETAKKAQNLVLPNRKSPSPVAPHPST
  FVATPASHNLVNQTNGTTKESALLLHVLLMVPDGKDFISGESEKQSPCNVYLNCKLFSTE
  EVTRSVIAWGTTQPVFNFSQVIPVSLSSKYLERLKNNVMVIETWNKVRSPGQDKLLGLVK
  LPLHQFYMSFKDAKISRLLLDAQYPVVAVDSYMPVIDVFSGHQNGSLRVFLAMGSSNQIM
  ALQRLKNEEGTLPPFSPRPAHFLDQPTAASVAMAEDRGNGLMEHCFEIHIEMVKGLAPLQ
  ATVWGEADCYVQYYFPVQHSQSSVLKGPEFLENGITLKPFRTATTLCVPDPIFNSEHHHS
  LLLPAEVPVQRLLLSAFSAQGLVPGGGVQFEIWCRYYYPNVRDQKVAKGTLPLSRICAMV
  TTQHREDVGIQTFNLPLTPRIENRKELRNQSSGLLDVGLRYRRSPRTAEGVLAARTVSIS
  VQIIRACGLQAAAKALAEREPALQFSATVGVNASVTTHLSFLPQGEQRRTHPVACSFCPE
  FSHHVEFTCNLVTQHCSGEACFLAELLEFAEVIFAVYHENTKSASDIISIESCKEYLLGV
  VKVPTKELLIKRSGITGWYPIILPEDGGLPHGLELMQKIVGGLELSISFTHRGDRERVLE
  AAEHLGWSFENSLKDFVRMDEGEPATVTISTPRLWLPIHCVLLAGHNHIHKNTYCYLRYK
  FYDHEAFWTPLKKPKESVNKKQIMVTFKASKRAEVTRGPSLLWYFREERLEIQVWRAYGN
  DSVERPHQTDSWIGSAYVDLARLGERSARTLTVSGVYPLFGRNASNLSGAALRVHVVLSS
  LSSHLEPTHELDSMDCSSHSESEQLPRRNDEVQLSPPEVISCHQKSPASTQVPCSSTTAE
  VRLTQEGPADLDGTFAVSILVERAMHLSLKGSPLTERKVSIPSCCVSFATADESSPVYTQ
  VVENTDSPIWNFQQQSRLSKELLLDPQQTLVFKVWHKGDEERVIGFASVDLSPLLSGFQF
  VCGWYNITDFSGECQGQIKVAVSPLESLIHFKEERQARRGVETSKSLIPIYSPFSFPASD
  TYAAFSSHMARQTLDQLAHASSKELDFSSPGRSDTTRSQASRHEEHVQNIRRFHESLHLQ
  GEAPLPCDDKLTTSPLSSQTSILTSLRKNLSELDQIQRYFRQKLTKPFLPLSPQTQTAIS
  QHQESCRDHLGPGASSLDPGSQCILEKSSNLVLQVSSLITDLQTITRDSQAALSSHRARS
  RSNKATTLPDAQDTEALQERCTMPDEPLVRAPDKGTDSPSPPPLEETSNGGRMLHESLRH
  AVPITRMQSSEDTEAGPAYSDEDYEEDIIEPRTLNEITTVTDKTSPWSSVISDTSEVISP
  QPDEVQREGPSCPSPGPFCREELMVKSSFLSSPERAVNPHLPRQGSPSQSLVACECEASK
  ARVGGESASANPQPIPCPTLSGAQQSSTFVGWSSPQTDQNKEPKSEAPAENEAATSELGD
  SADSFKKLPLNLASQSRRENHKGPPIDSSDIRQRQVTTGSETSTKQSLLLPGPIVVPNFF
  LPPQQLEASLRMLSLSATLPPAATTDQDKSEATRGALSQRPCRPRPNSLPLNLPEEETLR
  IARIFSSQYSQKD

• Sequence length: 2353

Pathways

Reactome:

Anchoring of the basal body to the plasma membrane

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Ankle flexion contracture	Likely pathogenic	rs1856949467	RCV001257347	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
C2CD3-related disorder	Likely pathogenic	rs2496420529, rs2496419846	RCV003416816 RCV003400343	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Joubert syndrome	Pathogenic	rs587777653, rs863225151	RCV000201616 RCV000201782	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Malignant tumor of urinary bladder	Likely pathogenic; Pathogenic	rs149366137	RCV005886952	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Orofaciodigital syndrome type 14	Likely pathogenic; Pathogenic	rs750328756, rs750700691, rs1565303622, rs2135493230, rs587777653, rs587777654, rs149366137, rs2496429489, rs2496410381, rs755686768, rs2496439292, rs1382351297, rs2496722228, rs1953091771, rs1174615027, rs1565237232	RCV002499813 RCV001780341 RCV001780699 RCV005410942 RCV000133545 RCV000133546 RCV000133547 RCV002510289 RCV003231052 RCV003338923 RCV003338924 RCV004587577 RCV003995165 RCV004547244 RCV000766221 RCV000766222	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Rudimentary fibula	Likely pathogenic	rs1856949467	RCV001257347	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Adrenocortical carcinoma, hereditary	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EBV-positive nodal T- and NK-cell lymphoma	Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL APLASIA OF THE VERMIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Conflicting classifications of pathogenicity; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GASTROINTESTINAL STROMAL TUMORS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Jeune thoracic dystrophy	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ORO-FACIAL DIGITAL SYNDROME TYPE 14	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OROFACIODIGITAL SYNDROME XIV	—	CTD, HPO CTD, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OROFACIODIGITAL SYNDROMES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign; Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	33797837	Associate	★☆☆☆☆ Found in Text Mining only
Aplasia of the epiglottis	Aplasia of the epiglottis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Atrial Septal Defects	Atrial Septal Defect	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Hypoplasia	Cerebellar Hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ciliopathies	Ciliopathies	BEFREE	30097616, 30988386		★☆☆☆☆ Found in Text Mining only
Ciliopathies	Ciliopathy	Pubtator	30097616, 33875766	Associate	★☆☆☆☆ Found in Text Mining only
Cleft Palate	Cleft palate	Pubtator	27604992	Associate	★☆☆☆☆ Found in Text Mining only
Coloboma of optic disc	Coloboma of optic disc	HPO_DG			★☆☆☆☆ Found in Text Mining only
Coloboma of the Retina	Retinal coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dandy-Walker Syndrome	Dandy-Walker Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epispadias	Epispadias	HPO_DG			★☆☆☆☆ Found in Text Mining only
Familial aplasia of the vermis	Cerebellar vermis agenesis	CLINVAR_DG	26092869		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Fundus coloboma	Fundus Coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gastrointestinal Stromal Sarcoma	Gastrointestinal stromal tumor	CTD_human_DG	27793025		★☆☆☆☆ Found in Text Mining only
Gastrointestinal Stromal Tumors	Gastrointestinal stromal tumor	CTD_human_DG	27793025		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Holoprosencephaly	Holoprosencephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	24997988	Associate	★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	BEFREE	27094867		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mohr Syndrome	Mohr Syndrome	CTD_human_DG	24997988		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	22807096		★☆☆☆☆ Found in Text Mining only
Occipital Encephalocele	Occipital Encephalocele	HPO_DG			★☆☆☆☆ Found in Text Mining only
Orofaciodigital Syndrome I	Orofaciodigital Syndrome	BEFREE	24997988		★☆☆☆☆ Found in Text Mining only
Orofaciodigital Syndrome I	Orofaciodigital Syndrome	CTD_human_DG	24997988		★☆☆☆☆ Found in Text Mining only
Orofaciodigital Syndrome I	Orofaciodigital Syndrome	GENOMICS_ENGLAND_DG	24997988, 26044959, 27094867		★☆☆☆☆ Found in Text Mining only
Orofaciodigital syndrome type 14	Orofaciodigital Syndrome	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
OROFACIODIGITAL SYNDROME XIV	Orofaciodigital Syndrome	ORPHANET_DG	24997988		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OROFACIODIGITAL SYNDROME XIV	Orofaciodigital Syndrome	UNIPROT_DG	24997988		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OROFACIODIGITAL SYNDROME XIV	Orofaciodigital Syndrome	GENOMICS_ENGLAND_DG	24997988, 26044959, 27094867		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OROFACIODIGITAL SYNDROME XIV	Orofaciodigital Syndrome	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OROFACIODIGITAL SYNDROME XIV	Orofaciodigital Syndrome	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Orofaciodigital Syndromes	Orofaciodigital syndrome	BEFREE	24997988, 27094867		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Orofaciodigital Syndromes	Orofaciodigital syndrome	CTD_human_DG	24997988		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Orofaciodigital Syndromes	Orofaciodigital syndrome	Pubtator	24997988, 30097616	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteochondrodysplasias	Osteochondrodysplasia	BEFREE	27094867		★☆☆☆☆ Found in Text Mining only
Osteofibrous Dysplasia	Osteofibrous Dysplasia	BEFREE	26044959, 30097616		★☆☆☆☆ Found in Text Mining only
Patent ductus arteriosus	Patent ductus arteriosus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Penis agenesis	Penis Agenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Periventricular Nodular Heterotopia	Periventricular Nodular Heterotopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polydactyly	Polydactyly	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
POLYDACTYLY, POSTAXIAL	Polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polymicrogyria	Polymicrogyria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Posteriorly rotated ear	Posteriorly Rotated Ear	HPO_DG			★☆☆☆☆ Found in Text Mining only
Radial polydactyly	Radial Polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Retinitis	Retinitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Saldino-Noonan Syndrome	Asphyxiating thoracic dystrophy	GENOMICS_ENGLAND_DG	24997988, 26044959, 27094867		★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Skeletal dysplasia	Skeletal Dysplasia	BEFREE	27094867		★☆☆☆☆ Found in Text Mining only
Trigonocephaly	Trigonocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ventricular Septal Defects	Ventricular septal defect	HPO_DG			★☆☆☆☆ Found in Text Mining only