SH3BP4
Chr 2SH3 domain binding protein 4
Also known as: BOG25, TTP
This protein regulates clathrin-mediated endocytosis of transferrin receptors and acts as a negative regulator of mTOR signaling by preventing Rag GTPase complex activation, thereby controlling cell growth, proliferation, and autophagy. Mutations cause autosomal recessive neurodevelopmental disorder with progressive microcephaly, seizures, and brain atrophy. The gene shows tolerance to loss-of-function variants (low pLI score), consistent with the recessive inheritance pattern observed clinically.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
ClinVar Variant Classifications
225 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 | 47 | 0 | 47 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 132 | 8 | 0 | 140 |
Likely Benign | 0 | 8 | 1 | 7 | 16 |
Benign | 0 | 1 | 0 | 6 | 7 |
| Total | 0 | 141 | 57 | 13 | 211 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SH3BP4 · 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