ARHGAP39
Chr 8Rho GTPase activating protein 39
Also known as: CrGAP, Vilse
ARHGAP39 encodes a protein with GTPase activator activity that functions in postsynaptic organization at glutamatergic synapses. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and seizures. The gene shows high constraint against loss-of-function variants (LOEUF 0.45), consistent with its essential role in synaptic function.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is dominant-negative.
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
297 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 51 | 0 | 51 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 184 | 14 | 0 | 198 |
Likely Benign | 0 | 9 | 2 | 3 | 14 |
Benign | 0 | 0 | 2 | 2 | 4 |
| Total | 0 | 193 | 74 | 5 | 272 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ARHGAP39 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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