C2CD3

Chr 11AR

C2 domain containing 3 centriole elongation regulator

Also known as: OFD14

The C2CD3 protein regulates centriole elongation and promotes assembly of centriolar distal appendages, which are required for primary cilium formation and sonic hedgehog signaling. Mutations cause orofaciodigital syndrome XIV, an autosomal recessive ciliopathy characterized by malformations of the oral cavity, face, and digits. The gene shows minimal constraint against loss-of-function variants (very low pLI score), consistent with its recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.641 OMIM phenotype
Clinical SummaryC2CD3
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Gene-Disease Validity (ClinGen)
orofaciodigital syndrome type 14 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
54 unique Pathogenic / Likely Pathogenic· 231 VUS of 500 total submissions
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GeneReview available — C2CD3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.64LOEUF
pLI 0.000
Z-score 4.40
OE 0.50 (0.400.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.53Z-score
OE missense 0.95 (0.901.00)
980 obs / 1028.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.50 (0.400.64)
00.351.4
Missense OE0.95 (0.901.00)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 46 / 91.4Missense obs/exp: 980 / 1028.3Syn Z: -0.05
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongC2CD3-related orofaciodigital syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6454th %ile
GOF
0.5366th %ile
LOF
0.4430th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic15
VUS231
Likely Benign196
Benign4
Conflicting15
39
Pathogenic
15
Likely Pathogenic
231
VUS
196
Likely Benign
4
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
35
2
2
0
39
Likely Pathogenic
11
2
2
0
15
VUS
1
213
13
4
231
Likely Benign
0
11
56
129
196
Benign
0
1
1
2
4
Conflicting
15
Total4722974135500

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

C2CD3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC