RAB9B

Chr X

RAB9B, 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.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
MultiplemechanismLOEUF 0.68
Clinical SummaryRAB9B
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.73) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.68LOEUF
pLI 0.734
Z-score 1.94
OE 0.00 (0.000.68)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
1.80Z-score
OE missense 0.42 (0.320.57)
33 obs / 77.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.68)
00.351.4
Missense OE0.42 (0.320.57)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 0 / 4.4Missense obs/exp: 33 / 77.8Syn Z: -0.67
DN
0.6454th %ile
GOF
0.73top 25%
LOF
0.4038th %ile

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.

GOFprediction above median
DNprediction 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

RAB9B · 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.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found