RAB32

Chr 6AD

RAB32, member RAS oncogene family

Also known as: PARK26

NCBI Gene: 10981 ENSG00000118508 UniProt: Q13637 OMIM: 612906

This small GTPase regulates intracellular membrane trafficking, anchors protein kinase A to mitochondria, and controls mitochondrial fission, phagosome maturation, and melanosome biogenesis. Mutations cause autosomal dominant Parkinson disease 26, with the gene showing low constraint to loss-of-function variants (pLI 0.0006, LOEUF 1.29). The protein also stimulates LRRK2-mediated phosphorylation of RAB10, linking it to other Parkinson disease pathways.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene anchors the type II regulatory subunit of protein kinase A to the mitochondrion and aids in mitochondrial fission. The encoded protein also appears to be involved in autophagy and melanosome secretion. Variations in this gene may be linked to leprosy. [provided by RefSeq, Dec 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Parkinson disease 26, susceptibility to}MIM #620923

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.29

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — RAB32

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.29LOEUF

pLI 0.001

Z-score 0.96

OE 0.66 (0.36–1.29)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.26Z-score

OE missense 1.06 (0.92–1.23)

132 obs / 124.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.66 (0.36–1.29)

0≤0.351.4

Missense OE?1.06 (0.92–1.23)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 6 / 9.1Missense obs/exp: 132 / 124.0Syn Z: -0.60

Background carrier burden — how many people carry a rare variant somewhere in RAB32?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

307 rare PASS variants

Rare truncating (LoF)

1 in 2,700

58 rare PASS variants

Rare synonymous (reference)

1 in 580

122 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RAB32. 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)	~556k	1 in 250	1 in 2,600
South Asian	~43k	1 in 190	1 in 3,200
Remaining (unassigned)	~30k	1 in 140	1 in 2,900
European (Finnish)	~27k	1 in 620	1 in 2,800
Admixed American	~22k	1 in 230	1 in 2,100
African / African American	~21k	1 in 190	≈ 1 in 6,000
East Asian	~20k	1 in 400	1 in 1,800
Ashkenazi Jewish	~13k	≈ 1 in 13,000	≈ 1 in 6,400
Middle Eastern	~2,884	1 in 140	≈ 1 in 710

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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓