RAB27A

Chr 15AR

RAB27A, member RAS oncogene family

Also known as: GS2, HsT18676, RAB27, RAM

NCBI Gene: 5873 ENSG00000069974 UniProt: P51159 OMIM: 603868

RAB27A encodes a small GTPase that regulates vesicle trafficking in the late endocytic pathway and controls cytotoxic granule exocytosis in immune cells. Mutations cause Griscelli syndrome type 2, an autosomal recessive disorder characterized by partial albinism and severe immunodeficiency due to impaired lymphocyte function. The gene shows low constraint against loss-of-function variants (high LOEUF score), consistent with the recessive inheritance pattern where both alleles must be affected to cause disease.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene belongs to the small GTPase superfamily, Rab family. The protein is membrane-bound and may be involved in protein transport and small GTPase mediated signal transduction. Mutations in this gene are associated with Griscelli syndrome type 2. Alternative splicing occurs at this locus and four transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.651 OMIM phenotype

Clinical Summary— RAB27A

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Gene-Disease Validity (ClinGen)

Griscelli syndrome type 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

67 unique Pathogenic / Likely Pathogenic· 142 VUS of 351 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?

1.65LOEUF

pLI 0.000

Z-score 0.01

OE 1.00 (0.61–1.65)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.51Z-score

OE missense 1.13 (0.98–1.31)

135 obs / 119.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.00 (0.61–1.65)

0≤0.351.4

Missense OE?1.13 (0.98–1.31)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 10 / 10.0Missense obs/exp: 135 / 119.2Syn Z: 0.77

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveRAB27A-related Griscelli syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.76top 25%

GOF

0.76top 25%

LOF

0.2873th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

351 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44

Likely Pathogenic23

VUS142

Likely Benign92

Benign30

Conflicting15

Pathogenic

Likely Pathogenic

142

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	25	7	12	0	44
Likely Pathogenic	9	12	2	0	23
VUS	3	80	57	2	142
Likely Benign	0	2	46	44	92
Benign	0	0	29	1	30
Conflicting	—				15
Total	37	101	146	47	346

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap RAB27A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →