RAB24

Chr 5

RAB24, member RAS oncogene family

RAB24 encodes a small GTPase that regulates intracellular membrane trafficking and is required for clearance of late autophagic vacuoles under basal conditions. Mutations cause autosomal recessive intellectual disability with growth retardation and facial dysmorphism, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.629), suggesting some intolerance to complete protein loss.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
6
Pubs (1 yr)
61
P/LP submissions
0%
P/LP missense
0.63
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryRAB24
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
59 unique Pathogenic / Likely Pathogenic· 20 VUS of 95 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.63LOEUF
pLI 0.150
Z-score 2.56
OE 0.27 (0.130.63)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.71Z-score
OE missense 0.57 (0.470.69)
71 obs / 124.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.27 (0.130.63)
00.351.4
Missense OE0.57 (0.470.69)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 4 / 14.6Missense obs/exp: 71 / 124.6Syn Z: -0.61
DN
0.77top 25%
GOF
0.81top 10%
LOF
0.2288th %ile

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

GOFprediction above median
DNprediction 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

95 submitted variants in ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic6
VUS20
Likely Benign1
53
Pathogenic
6
Likely Pathogenic
20
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
53
0
53
Likely Pathogenic
0
0
6
0
6
VUS
0
13
7
0
20
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total01367080

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

View in ClinVar →

Protein Context — Lollipop Plot

RAB24 · 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

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC