RAB38

Chr 11

RAB38, member RAS oncogene family

Also known as: NY-MEL-1, rrGTPbp

NCBI Gene: 23682 ENSG00000123892 UniProt: P57729 OMIM: 606281

RAB38 encodes a small GTPase that regulates intracellular vesicle trafficking, particularly controlling melanosome biogenesis and the transport of melanogenic enzymes, and plays a role in phagosome maturation during pathogen engulfment. Mutations cause oculocutaneous albinism type 11, an autosomal recessive disorder characterized by reduced melanin production leading to hypopigmentation of skin, hair, and eyes. The gene shows low constraint against loss-of-function variants (pLI 0.002, LOEUF 1.36), consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Enables several functions, including AP-1 adaptor complex binding activity; AP-3 adaptor complex binding activity; and BLOC-2 complex binding activity. Involved in several processes, including endosome to melanosome transport; melanosome assembly; and phagosome acidification. Located in several cellular components, including cytoplasmic vesicle; lysosome; and mitochondria-associated endoplasmic reticulum membrane contact site. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.36

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.36LOEUF

pLI 0.002

Z-score 0.90

OE 0.65 (0.34–1.36)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.16Z-score

OE missense 1.04 (0.90–1.21)

126 obs / 121.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.65 (0.34–1.36)

0≤0.351.4

Missense OE?1.04 (0.90–1.21)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 5 / 7.7Missense obs/exp: 126 / 121.1Syn Z: 0.74

Background carrier burden — how many people carry a rare variant somewhere in RAB38?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

404 rare PASS variants

Rare truncating (LoF)

1 in 3,800

48 rare PASS variants

Rare synonymous (reference)

1 in 770

77 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RAB38. 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 210	1 in 7,200
South Asian	~43k	1 in 150	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 140	1 in 4,300
European (Finnish)	~27k	1 in 210	≈ 1 in 27,000
Admixed American	~22k	1 in 150	1 in 1,300
African / African American	~21k	1 in 75	1 in 940
East Asian	~20k	1 in 190	1 in 2,200
Ashkenazi Jewish	~13k	1 in 570	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 140	≈ 1 in 950

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 ↓