CCDC88A

Chr 2AR

coiled-coil and HOOK domain protein 88A

Also known as: APE, GIRDIN, GIV, GRDN, HkRP1, KIAA1212, PEHO, PEHOL

NCBI Gene: 55704 ENSG00000115355 UniProt: Q3V6T2 OMIM: 609736

The protein functions as a bifunctional modulator of G proteins, acting as both a guanine nucleotide exchange factor for G(i) alpha subunits and a dissociation inhibitor for G(s) alpha subunits, while also serving as an actin-binding protein essential for cytoskeleton integrity, cell migration, and ciliogenesis. Autosomal recessive mutations cause PEHO syndrome-like disorder, a severe early-onset neurodevelopmental condition. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.13), indicating strong evolutionary pressure to maintain protein function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the Girdin family of coiled-coil domain containing proteins. The encoded protein is an actin-binding protein that is activated by the serine/threonine kinase Akt and plays a role in cytoskeleton remodeling and cell migration. The encoded protein also enhances Akt signaling by mediating phosphoinositide 3-kinase (PI3K)-dependent activation of Akt by growth factor receptor tyrosine kinases and G protein-coupled receptors. Increased expression of this gene and phosphorylation of the encoded protein may play a role in cancer metastasis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

PEHO syndrome-likeMIM #617507

UniProtPEHO-like syndrome

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

0.13

LOEUF· LoF intol.

LOF

Mechanism· G2P