RASA3
Chr 13RAS p21 protein activator 3
Also known as: GAP1IP4BP, GAPIII
The protein functions as a GTPase-activating protein that negatively regulates Ras signaling by stimulating the GTPase activity of Ras p21 and binds inositol tetrakisphosphate with high affinity. Mutations in this gene cause microcephaly, seizures, intellectual disability, and cataracts, typically presenting in infancy with autosomal recessive inheritance. The gene is not highly constrained against loss-of-function variants, which is consistent with the recessive inheritance pattern observed clinically.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
311 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 | 1 | 0 | 114 | 0 | 115 |
Likely Pathogenic | 0 | 1 | 3 | 0 | 4 |
VUS | 0 | 123 | 20 | 0 | 143 |
Likely Benign | 0 | 4 | 4 | 5 | 13 |
Benign | 0 | 0 | 2 | 3 | 5 |
| Total | 1 | 128 | 143 | 8 | 280 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RASA3 · 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