CCDC88A
Chr 2ARcoiled-coil and HOOK domain protein 88A
Also known as: APE, GIRDIN, GIV, GRDN, HkRP1, KIAA1212, PEHO, PEHOL
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.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Moderately missense-constrained (top ~2.5%)
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CCDC88A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools