CCDC186

Chr 10

coiled-coil domain containing 186

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

NCBI Gene: 55088 ENSG00000165813 UniProt: Q7Z3E2 OMIM: 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.

OMIM ResearchSummary from RefSeq

Predicted to enable small GTPase binding activity. Predicted to be involved in vesicle cytoskeletal trafficking. Predicted to act upstream of or within insulin secretion involved in cellular response to glucose stimulus and response to bacterium. Predicted to be located in Golgi apparatus. Predicted to be active in trans-Golgi network. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.46

Clinical Summary— CCDC186

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 111 VUS of 129 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 OE?0.30 (0.20–0.46)

0≤0.351.4

Missense OE?0.79 (0.72–0.86)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 15 / 50.1Missense obs/exp: 347 / 439.4Syn Z: -0.07

This gene — mechanism propensity

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

129 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS111

Likely Benign4

Benign2

Pathogenic

111

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	1	0	0	1
Likely Pathogenic	0	0	0	0
VUS	4	107	0	111
Likely Benign	0	4	0	4
Benign	0	0	2	2
Total	5	111	2	118

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap CCDC186 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →