SH3BP2
Chr 4ADSH3 domain binding protein 2
Also known as: 3BP-2, 3BP2, CRBM, CRPM, RES4-23
The protein functions as a cytoplasmic adaptor that binds to SH3 domains of signaling proteins including ABL1 and SYK tyrosine kinases, positively regulating transcriptional activity in immune cells. Mutations cause cherubism, a rare bone disorder characterized by painless bilateral enlargement of the jaws that typically manifests in early childhood. Inheritance is autosomal dominant, and the gene shows very low constraint against loss-of-function variants.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
400 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 | 21 | 0 | 21 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 8 | 176 | 11 | 1 | 196 |
Likely Benign | 0 | 2 | 74 | 77 | 153 |
Benign | 0 | 0 | 7 | 0 | 7 |
Conflicting | — | 3 | |||
| Total | 8 | 178 | 115 | 78 | 382 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SH3BP2 · 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
External Resources
Links to major genomics databases and tools