SH3BP5L

Chr 1

SH3 binding domain protein 5 like

The SH3BP5L protein functions as a guanine nucleotide exchange factor for RAB11A and is involved in intracellular signal transduction in the cytoplasm. Mutations in this gene cause autosomal recessive neurodevelopmental disorder with epilepsy and brain atrophy. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.596), and the associated disorder involves the nervous system with seizures and structural brain abnormalities.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.60
Clinical SummarySH3BP5L
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.60LOEUF
pLI 0.046
Z-score 2.89
OE 0.30 (0.160.60)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.68Z-score
OE missense 0.71 (0.630.80)
189 obs / 266.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.30 (0.160.60)
00.351.4
Missense OE0.71 (0.630.80)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 6 / 19.9Missense obs/exp: 189 / 266.3Syn Z: 0.66
DN
0.78top 25%
GOF
0.77top 25%
LOF
0.2288th %ile

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.

DNprediction above median
GOFprediction above median

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SH3BP5L · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →