RAB9B
Chr XRAB9B, member RAS oncogene family
Also known as: RAB9L, Rab-9L
RAB9B encodes a small GTPase that regulates intracellular membrane trafficking, specifically controlling transport of proteins between endosomes and the trans-Golgi network by cycling between inactive GDP-bound and active GTP-bound forms. Mutations cause autosomal dominant neurological disease through a predicted gain-of-function mechanism. The protein uses NDE1/NDEL1 as an effector to interact with the dynein motor complex for retrograde trafficking of late endosomes to the trans-Golgi network.
Some data sources returned errors (1)
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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 (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-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.
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 | 19 | 8 | 100 | 0 | 127 |
Likely Pathogenic | 19 | 50 | 13 | 3 | 85 |
VUS | 0 | 68 | 19 | 2 | 89 |
Likely Benign | 0 | 2 | 30 | 37 | 69 |
Benign | 0 | 2 | 15 | 4 | 21 |
Conflicting | — | 8 | |||
| Total | 38 | 130 | 177 | 46 | 399 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RAB9B · 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 →No open access results found
External Resources
Links to major genomics databases and tools