RAB27A

Chr 15AR

RAB27A, member RAS oncogene family

Also known as: GS2, HsT18676, RAB27, RAM

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.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Griscelli syndrome, type 2MIM #607624
AR
0
Active trials
87
Pubs (1 yr)
126
P/LP submissions
19%
P/LP missense
1.65
LOEUF
LOF
Mechanism· G2P
Clinical SummaryRAB27A
🧬
Gene-Disease Validity (ClinGen)
Griscelli syndrome type 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
83 unique Pathogenic / Likely Pathogenic· 150 VUS of 377 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.65LOEUF
pLI 0.000
Z-score 0.01
OE 1.00 (0.611.65)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.51Z-score
OE missense 1.13 (0.981.31)
135 obs / 119.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.00 (0.611.65)
00.351.4
Missense OE1.13 (0.981.31)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 10 / 10.0Missense obs/exp: 135 / 119.2Syn Z: 0.77
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveRAB27A-related Griscelli syndromeLOFAR

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

DN
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

377 submitted variants in ClinVar

Classification Summary

Pathogenic63
Likely Pathogenic20
VUS150
Likely Benign94
Benign30
Conflicting15
63
Pathogenic
20
Likely Pathogenic
150
VUS
94
Likely Benign
30
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
7
36
0
63
Likely Pathogenic
7
9
4
0
20
VUS
3
78
67
2
150
Likely Benign
0
2
48
44
94
Benign
0
0
29
1
30
Conflicting
15
Total309618447372

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

View in ClinVar →

Protein Context — Lollipop Plot

RAB27A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →