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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RAB25
RAB25, member RAS oncogene family
Chromosome 1 · 1q22
NCBI Gene: 57111Ensembl: ENSG00000132698.16HGNC: HGNC:18238UniProt: P57735
80PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
myosin V bindingprotein bindingplasma membranepseudopodiumatrial fibrillationParkinson diseaseneoplasmbreast cancer
✦AI Summary

RAB25 is an epithelial-cell-specific small GTPase that regulates intracellular membrane trafficking and endocytic recycling 1. As a member of the Rab GTPase family, RAB25 cycles between inactive GDP-bound and active GTP-bound states to recruit effectors controlling vesicle formation, movement, and fusion 1. The protein promotes invasive cell migration by localizing integrin α-V/β-1 at pseudopodial tips and regulates epithelial morphogenesis through claudin-4 localization at tight junctions 1. RAB25 interacts with myosin 5B to regulate transcytosis and functions in both fast and slow endocytic recycling pathways alongside Rab4 and Rab11 family members 2. RAB25 plays a complex, context-dependent role in cancer. It functions as an oncogene in ovarian cancer, where overexpression promotes aggressiveness and associates with drug resistance through selective clonal expansion 3. Conversely, RAB25 acts as a tumor suppressor in colon cancer, where decreased expression promotes neoplastic development 4. This dichotomy reflects RAB25's role in regulating growth factor and adhesion molecule recycling, with implications for proliferation and invasion 5. Recently, RAB25 was identified as activating noncanonical endoplasmic reticulum stress pathways in alcohol-associated liver disease through interaction with GCN1, promoting hepatic lipid metabolism dysregulation and inflammation 6. Additionally, RAB25 expression is downregulated in hypospadias foreskin tissue, suggesting developmental roles in urethral morphogenesis 7.

Sources cited
1
RAB25 is an epithelial-cell-specific Rab GTPase regulating endocytic machinery, integrin trafficking, and cellular energetics in cancer
PMID: 23176489
2
RAB25 is a Rab11 family member that regulates endocytic recycling cargo and interacts with ESCPE-1 and retromer complexes to control cancer cell migration
PMID: 37232246
3
RAB25 amplification is a distinctive genomic feature of drug-resistant clones in ovarian cancer, selected for during treatment
PMID: 41034582
4
RAB25 acts as a tumor suppressor in colon cancer, with decreased expression promoting neoplastic development and altered β1-integrin trafficking
PMID: 21063400
5
RAB25 and its binding partner RCP regulate endosome recycling of growth factor and adhesion molecule receptors to promote cancer progression
PMID: 30761451
6
RAB25 interacts with GCN1 to activate noncanonical ER stress pathways in alcohol-associated liver disease, promoting hepatic lipid dysfunction and inflammation
PMID: 40916695
7
RAB25 expression is downregulated in hypospadias foreskin tissue and may be involved in urethral development
PMID: 37246119
Disease Associationsⓘ20
atrial fibrillationOpen Targets
0.40Moderate
Parkinson diseaseOpen Targets
0.27Weak
neoplasmOpen Targets
0.11Weak
breast cancerOpen Targets
0.10Weak
cancerOpen Targets
0.10Suggestive
ovarian cancerOpen Targets
0.09Suggestive
head and neck squamous cell carcinomaOpen Targets
0.08Suggestive
oral squamous cell carcinomaOpen Targets
0.08Suggestive
posterior cortical atrophyOpen Targets
0.08Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.06Suggestive
esophageal squamous cell carcinomaOpen Targets
0.06Suggestive
glioblastoma multiformeOpen Targets
0.06Suggestive
X-linked diffuse leiomyomatosis - Alport syndromeOpen Targets
0.05Suggestive
esophageal cancerOpen Targets
0.05Suggestive
esophageal atresia/tracheoesophageal fistulaOpen Targets
0.05Suggestive
hypospadiasOpen Targets
0.05Suggestive
Barrett's esophagusOpen Targets
0.05Suggestive
esophageal adenocarcinomaOpen Targets
0.04Suggestive
gastroesophageal reflux diseaseOpen Targets
0.04Suggestive
non-small cell lung carcinomaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MYO5BProtein interaction97%RAB11FIP3Protein interaction97%RAB11FIP2Protein interaction97%RAB11FIP5Protein interaction97%OPTNProtein interaction97%RAB11FIP1Protein interaction93%
Tissue Expression6 tissues
Brain
100%
Lung
90%
Liver
7%
Bone Marrow
3%
Ovary
2%
Heart
0%
Gene Interaction Network
Click a node to explore
RAB25MYO5BRAB11FIP3RAB11FIP2RAB11FIP5OPTNRAB11FIP1
PROTEIN STRUCTURE
Preparing viewer…
PDB3TSO · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.25LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.88 [0.64–1.25]
RankingsWhere RAB25 stands among ~20K protein-coding genes
  • #5,958of 20,598
    Most Researched80
  • #13,211of 17,882
    Most Constrained (LOEUF)1.25
Genes detectedRAB25
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Rab25 and RCP in cancer progression.
PMID: 30761451
Arch Pharm Res · 2019
1.00
2
RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression.
PMID: 40916695
Clin Mol Hepatol · 2026
0.90
3
Tracking clonal evolution during treatment in ovarian cancer using cell-free DNA.
PMID: 41034582
Nature · 2025
0.80
4
Rab25 in cancer: a brief update.
PMID: 23176489
Biochem Soc Trans · 2012
0.70
5
A CRE that binds CREB and contributes to PKA-dependent regulation of the proximal promoter of human RAB25 gene.
PMID: 21075212
Int J Biochem Cell Biol · 2011
0.60