RAB3A

Chr 19AD

RAB3A, member RAS oncogene family

Also known as: SCA52

NCBI Gene: 5864ENSG00000105649UniProt: P20336OMIM: 179490

RAB3A encodes a small GTPase that controls regulated exocytosis and secretion by recruiting, tethering and docking secretory vesicles to the plasma membrane in neurons and other cell types. Mutations cause spinocerebellar ataxia 52 with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI = 0.95, LOEUF = 0.32), reflecting its essential role in vesicle trafficking.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.321 OMIM phenotype
Clinical Summary— RAB3A
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 19 VUS of 43 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.32LOEUF
pLI 0.946
Z-score 2.82
OE 0.00 (0.00–0.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.32Z-score
OE missense 0.47 (0.39–0.57)
71 obs / 151.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.32)
0≤0.351.4
Missense OE0.47 (0.39–0.57)
0≤0.61.4
Synonymous OE0.90
0≤1.21.6
LoF obs/exp: 0 / 9.2Missense obs/exp: 71 / 151.5Syn Z: 0.62
DN
0.7133th %ile
GOF
0.6932th %ile
LOF
0.4627th %ile

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, dominant-negative and gain-of-function). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.32
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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

43 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
VUS19
Likely Benign3
Benign2
11
Pathogenic
19
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
10
0
11
Likely Pathogenic
0
0
0
0
0
VUS
0
17
2
0
19
Likely Benign
0
0
2
1
3
Benign
0
0
1
1
2
Total01815235

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

View in ClinVar →

Protein Context — Lollipop Plot

RAB3A · 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