RAB9A

Chr X

RAB9A, member RAS oncogene family

Also known as: RAB9

NCBI Gene: 9367 ENSG00000123595 UniProt: P51151 OMIM: 300284

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.51

LOEUF

GOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in RAB9A?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 990

99 rare PASS variants

Rare truncating (LoF)

1 in 240,000

3 rare PASS variants

Rare synonymous (reference)

1 in 480

41 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RAB9A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 970	≈ 1 in 280,000
South Asian	~36k	1 in 690	none seen
Remaining (unassigned)	~31k	1 in 1,100	none seen
European (Finnish)	~27k	≈ 1 in 27,000	none seen
Admixed American	~23k	1 in 1,700	none seen
African / African American	~21k	1 in 1,000	none seen
East Asian	~20k	1 in 2,500	none seen
Ashkenazi Jewish	~13k	≈ 1 in 4,300	≈ 1 in 13,000
Middle Eastern	~2,758	≈ 1 in 550	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓