RAB38

Chr 11

RAB38, member RAS oncogene family

Also known as: NY-MEL-1, rrGTPbp

NCBI Gene: 23682ENSG00000123892UniProt: P57729OMIM: 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.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.36
Clinical Summary— RAB38
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 34 VUS of 62 total submissions
Explore recent and relevant literature in Research Assistant →

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 OE0.65 (0.34–1.36)
0≤0.351.4
Missense OE1.04 (0.90–1.21)
0≤0.61.4
Synonymous OE0.87
0≤1.21.6
LoF obs/exp: 5 / 7.7Missense obs/exp: 126 / 121.1Syn Z: 0.74
DN
0.85top 10%
GOF
0.81top 10%
LOF
0.2288th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
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

62 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS34
Likely Benign2
16
Pathogenic
1
Likely Pathogenic
34
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
1
0
1
VUS
0
32
2
0
34
Likely Benign
0
1
1
0
2
Benign
0
0
0
0
0
Total03320053

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

View in ClinVar →

Protein Context — Lollipop Plot

RAB38 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients