CCDC88C

Chr 14ADAR

coiled-coil domain containing 88C

This gene encodes a coiled-coil domain-containing protein that acts as a non-receptor guanine nucleotide exchange factor and negative regulator of canonical Wnt signaling by binding to Wnt receptor FZD7 and displacing dishevelled protein. Mutations cause autosomal recessive congenital hydrocephalus and possibly autosomal dominant spinocerebellar ataxia 40, affecting the central nervous system. The gene is highly constrained against loss-of-function variants (LOEUF 0.454), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.452 OMIM phenotypes
Clinical SummaryCCDC88C
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.000
Z-score 5.90
OE 0.34 (0.250.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.71Z-score
OE missense 0.94 (0.900.99)
1104 obs / 1172.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.250.45)
00.351.4
Missense OE0.94 (0.900.99)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 31 / 92.2Missense obs/exp: 1104 / 1172.2Syn Z: -0.72
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCCDC88C-related hydrocephalus, nonsyndromicLOFAR

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

DN
0.7327th %ile
GOF
0.6442th %ile
LOF
0.3647th %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.

Literature Evidence

GOFThe mutation was found by a combination of linkage analysis and whole-exome sequencing. Functional studies showed that mutant CCDC88C activated JNK (601158) and triggered apoptosis, consistent with a gain of function.PMID:25062847

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CCDC88C · 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 →