CCDC186

Chr 10

coiled-coil domain containing 186

Also known as: C10orf118, CCCP-1, CCCP1, golgin104

NCBI Gene: 55088ENSG00000165813UniProt: Q7Z3E2OMIM: 619249

CCDC186 encodes a protein predicted to bind small GTPases and regulate vesicle trafficking in the Golgi apparatus and trans-Golgi network, with involvement in insulin secretion and glucose response. The gene shows high constraint against loss-of-function variants (LOEUF 0.461), suggesting that mutations would likely cause significant developmental or physiological effects. However, no specific human disease phenotypes have been definitively associated with CCDC186 mutations to date.

OMIMResearchSummary from RefSeq
DNmechanismLOEUF 0.46
Clinical Summary— CCDC186
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 113 VUS of 157 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.001
Z-score 4.60
OE 0.30 (0.20–0.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.57Z-score
OE missense 0.79 (0.72–0.86)
347 obs / 439.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.30 (0.20–0.46)
0≤0.351.4
Missense OE0.79 (0.72–0.86)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 15 / 50.1Missense obs/exp: 347 / 439.4Syn Z: -0.07
DN
0.6842th %ile
GOF
0.4973th %ile
LOF
0.49top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

157 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic3
VUS113
Likely Benign4
Benign2
24
Pathogenic
3
Likely Pathogenic
113
VUS
4
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
23
0
24
Likely Pathogenic
0
0
3
0
3
VUS
4
107
2
0
113
Likely Benign
0
4
0
0
4
Benign
0
0
0
2
2
Total5111282146

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

View in ClinVar →

Protein Context — Lollipop Plot

CCDC186 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients