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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RAB3A
RAB3A, member RAS oncogene family
Chromosome 19 · 19p13.11
NCBI Gene: 5864Ensembl: ENSG00000105649.11HGNC: HGNC:9777UniProt: A0A024R7I7
104PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
lysosome localizationextracellular vesicleG protein activityregulated exocytosisNeurodevelopmental delayneurodegenerative diseasehepatocellular carcinomanon-small cell lung carcinoma
✦AI Summary

RAB3A encodes a small GTPase that plays a central role in regulated exocytosis and synaptic vesicle trafficking. As a key regulator of intracellular membrane trafficking, RAB3A cycles between inactive GDP-bound and active GTP-bound forms to control vesicle formation, movement, and fusion 1. The protein regulates calcium-dependent lysosome exocytosis and plasma membrane repair through interactions with effectors SYTL4 and myosin-9 2. In neuronal function, RAB3A is essential for anterograde axonal transport of synaptic vesicle precursors, forming complexes with motor adaptor MADD and kinesin motors KIF1A/1Bβ 3. During sperm exocytosis, GTP-bound RAB3A promotes secretion through its C-terminal domain, while GTP hydrolysis is mandatory for fusion pore opening 4. Disease relevance includes cerebellar ataxia caused by heterozygous RAB3A variants, particularly the recurrent p.Arg83Trp variant, which impairs GTPase activity and effector binding 1. Additionally, hyperphosphorylation of RAB3A by pathogenic LRRK2 in Parkinson's disease disrupts synaptic vesicle transport and synaptic protein distribution 3. RAB3A variants are also associated with amyotrophic lateral sclerosis, affecting motor-mediated transport 5.

Sources cited
1
RAB3A cycles between GDP/GTP-bound forms and causes cerebellar ataxia through variants like p.Arg83Trp
PMID: 40166812
2
RAB3A regulates calcium-dependent lysosome exocytosis and plasma membrane repair via SYTL4 and myosin-9 interactions
PMID: 27687479
3
RAB3A forms transport complexes with MADD and kinesin motors, and is hyperphosphorylated in Parkinson's disease
PMID: 38512027
4
GTP-bound RAB3A promotes sperm exocytosis via C-terminal domain, with GTP hydrolysis required for fusion
PMID: 25053757
5
RAB3A variants are associated with amyotrophic lateral sclerosis and affect motor-mediated transport
PMID: 36284339
Disease Associationsⓘ20
Neurodevelopmental delayOpen Targets
0.45Moderate
neurodegenerative diseaseOpen Targets
0.34Weak
hepatocellular carcinomaOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.06Suggestive
obesityOpen Targets
0.05Suggestive
overnutritionOpen Targets
0.05Suggestive
central nervous system cancerOpen Targets
0.04Suggestive
Alzheimer diseaseOpen Targets
0.03Suggestive
Parkinson diseaseOpen Targets
0.03Suggestive
glioblastoma multiformeOpen Targets
0.03Suggestive
ependymomaOpen Targets
0.03Suggestive
gliomaOpen Targets
0.03Suggestive
astrocytomaOpen Targets
0.02Suggestive
multiple sclerosisOpen Targets
0.02Suggestive
atypical teratoid rhabdoid tumorOpen Targets
0.02Suggestive
gastric cancerOpen Targets
0.02Suggestive
ataxia telangiectasiaOpen Targets
0.02Suggestive
oligodendrogliomaOpen Targets
0.02Suggestive
lung carcinomaOpen Targets
0.02Suggestive
Pathogenic Variants1
NM_002866.5(RAB3A):c.247C>T (p.Arg83Trp)Pathogenic
RAB3A-related condition|not provided
★☆☆☆2025→ Residue 83
View on ClinVar ↗
Related Genes
RPH3AProtein interaction100%SLC17A7Protein interaction100%RIMS2Protein interaction99%SLC17A8Protein interaction98%SLC18A3Protein interaction98%SLC18A2Protein interaction97%
Tissue Expression6 tissues
Brain
100%
Heart
29%
Ovary
11%
Liver
3%
Bone Marrow
2%
Lung
2%
Gene Interaction Network
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RAB3ARPH3ASLC17A7RIMS2SLC17A8SLC18A3SLC18A2
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P20336
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.47Moderately Constrained
pLIⓘ
0.99Intolerant
Observed/Expected LoF0.23 [0.12–0.47]
RankingsWhere RAB3A stands among ~20K protein-coding genes
  • #4,611of 20,598
    Most Researched104 · top quartile
  • #4,872of 5,498
    Most Pathogenic Variants1
  • #2,741of 17,882
    Most Constrained (LOEUF)0.47 · top quartile
Genes detectedRAB3A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
BDNF-induced local protein synthesis and synaptic plasticity.
PMID: 23602987
Neuropharmacology · 2014
1.00
2
Heterozygous RAB3A variants cause cerebellar ataxia by a partial loss-of-function mechanism.
PMID: 40166812
Brain · 2025
0.90
3
Metallothioneins and cancer.
PMID: 19689357
Curr Protein Pept Sci · 2009
0.80
4
Rab3a and Rab10 are regulators of lysosome exocytosis and plasma membrane repair.
PMID: 27687479
Small GTPases · 2018
0.70
5
Association of variants in the KIF1A gene with amyotrophic lateral sclerosis.
PMID: 36284339
Transl Neurodegener · 2022
0.60