RAB3B

Chr 1

RAB3B, member RAS oncogene family

NCBI Gene: 5865ENSG00000169213UniProt: P20337OMIM: 179510

RAB3B encodes a small GTPase that regulates synaptic vesicle trafficking and fusion at nerve terminals, particularly in dopaminergic synapses. Mutations cause autosomal recessive Cortical dysplasia, complex, with other brain malformations 8, characterized by complex brain malformations and developmental abnormalities. This gene follows autosomal recessive inheritance and affects critical neurodevelopmental processes during brain formation.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.75
Clinical Summary— RAB3B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
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ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 26 VUS of 37 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
0.75LOEUF
pLI 0.315
Z-score 2.04
OE 0.24 (0.10–0.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.94Z-score
OE missense 0.77 (0.66–0.91)
104 obs / 134.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.10–0.75)
0≤0.351.4
Missense OE0.77 (0.66–0.91)
0≤0.61.4
Synonymous OE0.86
0≤1.21.6
LoF obs/exp: 2 / 8.4Missense obs/exp: 104 / 134.9Syn Z: 0.81
DN
0.82top 10%
GOF
0.75top 25%
LOF
0.2776th %ile

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

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.

ClinVar Variant Classifications

37 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS26
Likely Benign1
6
Pathogenic
2
Likely Pathogenic
26
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
2
0
2
VUS
0
24
2
0
26
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total02411035

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

View in ClinVar →

Protein Context — Lollipop Plot

RAB3B · 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
Expression of Rab3b in Human Glioma: Influence on Cell Proliferation and Apoptosis.
Luo Q et al.·Curr Pharm Des
2021
Discovery and validation of RAB3B as a diagnostic biomarker for prostate cancer with serum PSA below 10 ng/mL based on a multi-omics study
Zhao C et al.·Cancer Cell Int
2025
Encoding gene RAB3B exists in linear chromosomal and circular extrachromosomal DNA and contributes to cisplatin resistance of hypopharyngeal squamous cell carcinoma via inducing autophagy
Lin C et al.·Cell Death Dis
2022
Single-cell and bulk transcriptome sequencing identifies circadian rhythm disruption and cluster-specific clinical insights in colorectal tumorigenesis
Liu C et al.·Discov Oncol
2025
Construction of a novel cuproptosis-related gene signature and integrative analyses in cholangiocarcinoma
Wang L et al.·Heliyon
2025
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