SH3BP1
Chr 22SH3 domain binding protein 1
Also known as: ARHGAP43
The protein functions as a GTPase activating protein that specifically inactivates RAC1 and CDC42, regulating actin cytoskeleton dynamics, cell migration, epithelial junction formation, and angiogenesis. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, developmental delay, and dysmorphic features. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.54), suggesting some tolerance to protein loss.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is gain-of-function.
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
176 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 | 19 | 0 | 19 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 119 | 2 | 0 | 121 |
Likely Benign | 0 | 2 | 1 | 1 | 4 |
Benign | 0 | 0 | 1 | 1 | 2 |
Conflicting | — | 1 | |||
| Total | 0 | 121 | 24 | 2 | 148 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SH3BP1 · 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