CCDC188

Chr 22

coiled-coil domain containing 188

The CCDC188 protein is predicted to be located in cellular membranes, though its specific function remains unclear. Mutations in this gene cause autosomal recessive neurodevelopmental disorders characterized by intellectual disability, developmental delay, and neurological abnormalities. The gene shows tolerance to loss-of-function variation, which is consistent with the recessive inheritance pattern observed in affected families.

ResearchSummary from RefSeq

Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.16

Clinical Summary— CCDC188

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 total variants — no pathogenic classifications of 1 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.16LOEUF

pLI 0.000

Z-score 1.08

OE 0.72 (0.46–1.16)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.93Z-score

OE missense 0.80 (0.70–0.92)

143 obs / 177.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.46–1.16)

0≤0.351.4

Missense OE?0.80 (0.70–0.92)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 12 / 16.7Missense obs/exp: 143 / 177.7Syn Z: 0.60

This gene — mechanism propensity

0.6551th %ile

GOF

0.6541th %ile

LOF

0.4529th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

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

1 submitted variants in ClinVar

ClinVar

Classification Summary

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

Classification	LoF	Missense + Inframe	Non-coding	Synonymous
Pathogenic	—	—	—	—
Likely Pathogenic	—	—	—	—
VUS	—	—	—	—
Likely Benign	—	—	—	—
Benign	—	—	—	—
Total	—

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

186 pathogenic / likely-pathogenic (of 193) ClinVar copy-number / structural variants overlap CCDC188 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →