RAB9A

Chr X

RAB9A, member RAS oncogene family

Also known as: RAB9

RAB9A encodes a small GTPase that regulates intracellular membrane trafficking, specifically controlling transport of proteins between endosomes and the trans-Golgi network. Mutations cause autosomal dominant intellectual disability with hypotonia and behavioral abnormalities. This gene is highly constrained against loss-of-function variants (pLI = 0.83, LOEUF = 0.51), indicating that haploinsufficiency is likely not well-tolerated in the general population.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 0.51
Clinical SummaryRAB9A
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.832
Z-score 2.25
OE 0.00 (0.000.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.28Z-score
OE missense 0.59 (0.460.76)
45 obs / 76.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.51)
00.351.4
Missense OE0.59 (0.460.76)
00.61.4
Synonymous OE0.78
01.21.6
LoF obs/exp: 0 / 5.9Missense obs/exp: 45 / 76.4Syn Z: 0.96
DN
0.6064th %ile
GOF
0.7029th %ile
LOF
0.4627th %ile

The highest-scoring mechanism for this gene is gain-of-function.

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

RAB9A · 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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