CCDC8

Chr 19

coiled-coil domain containing 8 subunit of 3M complex

Also known as: 3M3, PPP1R20, p90

This gene encodes a coiled-coil domain-containing protein. The encoded protein functions as a cofactor required for p53-mediated apoptosis following DNA damage, and may also play a role in growth through interactions with the cytoskeletal adaptor protein obscurin-like 1. Mutations in this gene are a cause of 3M syndrome-3 (3M3). [provided by RefSeq, Dec 2011]

GeneReviewsResearchGenerating clinical summary…
LOFmechanismLOEUF 0.83
Clinical SummaryCCDC8
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 157 VUS of 247 total submissions
📖
GeneReview available — CCDC8
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.83LOEUF
pLI 0.254
Z-score 1.88
OE 0.26 (0.110.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.16Z-score
OE missense 1.03 (0.941.13)
319 obs / 311.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.26 (0.110.83)
00.351.4
Missense OE?1.03 (0.941.13)
00.61.4
Synonymous OE?1.14
01.21.6
LoF obs/exp: 2 / 7.6Missense obs/exp: 319 / 311.1Syn Z: -1.24
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCCDC8-related 3-M syndromeLOFAR

This gene — mechanism propensity

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

DN
0.6064th %ile
GOF
0.6834th %ile
LOF
0.3356th %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.

ClinVar Variant Classifications

247 submitted variants in ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic11
VUS157
Likely Benign60
Benign8
Conflicting10
1
Pathogenic
11
Likely Pathogenic
157
VUS
60
Likely Benign
8
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
0
0
1
Likely Pathogenic
11
0
0
0
11
VUS
11
144
0
2
157
Likely Benign
0
16
0
44
60
Benign
0
1
2
5
8
Conflicting
10
Total23161251247

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap CCDC8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

CCDC8 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →