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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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RAB3C
RAB3C, member RAS oncogene family
Chromosome 5 · 5q11.2
NCBI Gene: 115827Ensembl: ENSG00000152932.8HGNC: HGNC:30269UniProt: Q96E17
33PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GTPase activityprotein bindingmyosin V bindingantigen processing and presentationneurodegenerative diseaseDNA methylationmood disordermajor depressive disorder
✦AI Summary

RAB3C is a small GTPase belonging to the Rab3 family that regulates intracellular membrane trafficking by cycling between inactive GDP-bound and active GTP-bound forms 1. The protein localizes to chromosome 5 and is expressed in brain, placenta, and lung tissues 1. RAB3C functions in regulated exocytosis, controlling vesicular transport and membrane fusion across multiple cellular contexts 2. In spermatogenesis, RAB3C localizes to the manchette structure, postacrosomal region, neck, and midpiece, playing a critical role in sperm head and tail morphogenesis; delocalization of RAB3C is associated with morphological sperm defects linked to SEPT14 mutations 3. RAB3C also functions in endocytosis and autophagy of TGF-β receptor 2, with deficiency exacerbating thoracic aortic aneurysm development in Marfan syndrome models 4. Clinically, RAB3C is upregulated in adrenal medullary hyperplasia associated with secondary hypertension 5 and in non-small cell lung cancer, where elevated expression via the circ_0070659/miR-377/RAB3C axis promotes tumor proliferation, migration, and invasion 6. RAB3C overexpression has been observed in various cancers including gliomas and colon cancers, correlating with decreased survival and advanced pathological stage 7. These findings position RAB3C as a multifunctional regulator of membrane dynamics with significant pathophysiological implications.

Sources cited
1
RAB3C gene localization to chromosome 5q13, tissue expression patterns in brain/placenta/lung, and classification as a Rab3 family member
PMID: 12296628
2
RAB3C role in regulating synaptic vesicle neurotransmitter release and exocytosis
PMID: 10488439
3
RAB3C localization patterns in sperm manchette, postacrosomal region, neck and midpiece; association with sperm morphological defects in SEPT14 mutations
PMID: 36295569
4
RAB3C-mediated endocytosis and autophagy of TGF-β receptor 2; involvement in Marfan syndrome aneurysm development
PMID: 39585648
5
RAB3C upregulation in adrenal medullary hyperplasia tissue associated with secondary hypertension
PMID: 36583008
6
RAB3C overexpression in non-small cell lung cancer promotes proliferation, migration and invasion via circ_0070659/miR-377/RAB3C pathway
PMID: 36694911
7
RAB3C overexpression in colon cancers and association with increased proliferation, migration, invasiveness, and decreased survival
PMID: 33982832
8
RAB3C is a substrate of DENN/MADD guanine nucleotide exchange factor with mutations affecting Rab GTPase activation
PMID: 40812422
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.46Moderate
DNA methylationOpen Targets
0.31Weak
mood disorderOpen Targets
0.30Weak
major depressive disorderOpen Targets
0.30Weak
type 2 diabetes mellitusOpen Targets
0.28Weak
central nervous system infectionOpen Targets
0.28Weak
bile duct disorderOpen Targets
0.26Weak
preeclampsiaOpen Targets
0.25Weak
type 1 diabetes mellitusOpen Targets
0.25Weak
gram-negative bacterial infectionsOpen Targets
0.23Weak
male reproductive system diseaseOpen Targets
0.14Weak
breast carcinomaOpen Targets
0.10Suggestive
diabetes mellitusOpen Targets
0.08Suggestive
primary familial polycythemia due to EPO receptor mutationOpen Targets
0.06Suggestive
Pyruvate kinase hyperactivityOpen Targets
0.05Suggestive
glioblastoma multiformeOpen Targets
0.05Suggestive
hemolytic anemia due to diphosphoglycerate mutase deficiencyOpen Targets
0.05Suggestive
erythrocytosis, familial, 6Open Targets
0.05Suggestive
erythrocytosis, familial, 3Open Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
REP15Protein interaction92%RIMS2Protein interaction84%RIMS1Protein interaction84%RIMBP2Protein interaction84%RPH3AProtein interaction81%TSPOAP1Protein interaction81%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
8%
Ovary
2%
Heart
2%
Liver
1%
Lung
0%
Gene Interaction Network
Click a node to explore
RAB3CREP15RIMS2RIMS1RIMBP2RPH3ATSPOAP1
PROTEIN STRUCTURE
Preparing viewer…
PDB6Y7G · 2.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.07LoF Tolerant
pLIⓘ
0.02Tolerant
Observed/Expected LoF0.59 [0.35–1.07]
RankingsWhere RAB3C stands among ~20K protein-coding genes
  • #11,394of 20,598
    Most Researched33
  • #10,789of 17,882
    Most Constrained (LOEUF)1.07
Genes detectedRAB3C
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PIEZO1 attenuates Marfan syndrome aneurysm development through TGF-β signaling pathway inhibition via TGFBR2.
PMID: 39585648
Eur Heart J · 2025
1.00
2
Localization Patterns of RAB3C Are Associated with Murine and Human Sperm Formation.
PMID: 36295569
Medicina (Kaunas) · 2022
0.90
3
Cloning, mapping, and characterization of the human Rab3C gene.
PMID: 12296628
Biochem Genet · 2002
0.80
4
Rab3 proteins and cancer: Exit strategies.
PMID: 33982832
J Cell Biochem · 2021
0.70
5
Molecular analysis of neurotransmitter release.
PMID: 10488439
Essays Biochem · 1998
0.60