CCDC88C

Chr 14

coiled-coil and HOOK domain protein 88C

Also known as: DAPLE, HKRP2, HYC1, KIAA1509, SCA40

NCBI Gene: 440193 ENSG00000015133 UniProt: Q9P219

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a ubiquitously expressed coiled-coil domain-containing protein that interacts with the dishevelled protein and is a negative regulator of the Wnt signalling pathway. The protein encoded by this gene has a PDZ-domain binding motif in its C-terminus with which it interacts with the dishevelled protein. Dishevelled is a scaffold protein involved in the regulation of the Wnt signaling pathway. The Wnt signaling pathway plays an important role in embryonic development, tissue maintenance, and cancer progression. Mutations in this gene cause autosomal recessive, primary non-syndromic congenital hydrocephalus; a condition characterized by excessive accumulation of cerebrospinal fluid in the ventricles of the brain. [provided by RefSeq, Jan 2013]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHydrocephalus, congenital, 1

UniProtSpinocerebellar ataxia 40

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.45

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429