RAB17
Chr 2RAB17, member RAS oncogene family
RAB17 encodes an epithelial cell-specific small GTPase that regulates intracellular membrane trafficking, particularly controlling transcytosis (the directed movement of materials through cells) and melanosome transport, and is required for dendrite and dendritic spine development. Mutations in RAB17 cause autosomal recessive infantile-onset symptomatic epilepsy syndrome, which presents in early infancy with seizures and developmental delays. The gene shows low constraint to loss-of-function variants, consistent with its recessive inheritance pattern.
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
135 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 | 76 | 0 | 76 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 35 | 12 | 0 | 47 |
Likely Benign | 0 | 2 | 1 | 0 | 3 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 37 | 90 | 0 | 127 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RAB17 · 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