RAB9A

Chr X

RAB9A, member RAS oncogene family

Also known as: RAB9

NCBI Gene: 9367 ENSG00000123595 UniProt: P51151

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.

ResearchSummary from RefSeq, UniProt

Enables G protein activity; GDP binding activity; and GTP binding activity. Involved in positive regulation of exocytosis; receptor-mediated endocytosis; and regulation of protein localization. Located in late endosome; lysosome; and phagocytic vesicle. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.51

Clinical Summary— RAB9A

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.

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ClinVar Variants

16 VUS of 31 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.832

Z-score 2.25

OE 0.00 (0.00–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.28Z-score

OE missense 0.59 (0.46–0.76)

45 obs / 76.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.51)

0≤0.351.4

Missense OE?0.59 (0.46–0.76)

0≤0.61.4

Synonymous OE?0.78

0≤1.21.6

LoF obs/exp: 0 / 5.9Missense obs/exp: 45 / 76.4Syn Z: 0.96

This gene — mechanism propensity

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

31 submitted variants in ClinVar

ClinVar

Classification Summary

VUS16

Likely Benign1

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	15	1	0	16
Likely Benign	0	0	1	1
Benign	0	0	1	1
Total	15	1	2	18

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

77 pathogenic / likely-pathogenic (of 86) ClinVar copy-number / structural variants overlap RAB9A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →