RAB24

Chr 5

RAB24, member RAS oncogene family

NCBI Gene: 53917 ENSG00000169228 UniProt: Q969Q5 OMIM: 612415

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.

OMIM ResearchSummary from RefSeq, UniProt

RAB24 is a small GTPase of the Rab subfamily of Ras-related proteins that regulate intracellular protein trafficking (Olkkonen et al., 1993 [PubMed 8126105]).[supplied by OMIM, Aug 2009]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.63

Clinical Summary— RAB24

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

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ClinVar Variants

13 VUS of 28 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?

0.63LOEUF

pLI 0.150

Z-score 2.56

OE 0.27 (0.13–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.71Z-score

OE missense 0.57 (0.47–0.69)

71 obs / 124.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.13–0.63)

0≤0.351.4

Missense OE?0.57 (0.47–0.69)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 4 / 14.6Missense obs/exp: 71 / 124.6Syn Z: -0.61

This gene — mechanism propensity

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

28 submitted variants in ClinVar

ClinVar

Classification Summary

VUS13

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	13	13
Likely Benign	0	0
Benign	0	0
Total	13	13

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

View in ClinVar →

61 pathogenic / likely-pathogenic (of 69) ClinVar copy-number / structural variants overlap RAB24 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →