RAB11A
Chr 15RAB11A, member RAS oncogene family
Also known as: YL8
The protein is a small GTPase that regulates both constitutive and regulated secretory pathways and protein transport at the cell membrane. Mutations cause autosomal dominant neurodevelopmental disorder with intellectual disability, seizures, and brain malformations through loss of function mechanisms. The high pLI score (0.99) and low LOEUF score (0.21) indicate the gene is highly intolerant to loss-of-function variants.
Moderate evidence — consider for supplementary testing
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
141 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 | 8 | 0 | 8 |
Likely Pathogenic | 0 | 2 | 2 | 0 | 4 |
VUS | 0 | 42 | 8 | 1 | 51 |
Likely Benign | 0 | 5 | 21 | 32 | 58 |
Benign | 0 | 1 | 3 | 4 | 8 |
Conflicting | — | 3 | |||
| Total | 0 | 50 | 42 | 37 | 132 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RAB11A · 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