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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RAB5B
RAB5B, member RAS oncogene family
Chromosome 12 · 12q13.2
NCBI Gene: 5869Ensembl: ENSG00000111540.17HGNC: HGNC:9784UniProt: P61020
104PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GTPase activityprotein bindingextracellular exosomeGDP bindinghypothyroidismtype 1 diabetes mellitusneurodegenerative diseasegastroesophageal reflux disease
✦AI Summary

RAB5B is a small GTPase that functions as a key regulator of early endocytic trafficking. It localizes to the plasma membrane and early endosomes 1, where it cycles between inactive GDP-bound and active GTP-bound states to recruit effector proteins responsible for vesicle formation, movement, and fusion 23. RAB5B is specifically required for EEA1 recruitment to early endosomes and mediates endocytosis of growth factors like EGF and transferrin 23. Dysregulation of RAB5B is associated with multiple disease pathologies. In cancer, RAB5B expression correlates with tumor progression across diverse malignancies and modulates cell migration and adhesion 4. In pancreatic cancer, RAB5B participates in perineural invasion through extracellular vesicle-mediated circRNA delivery 5, while in breast cancer, RAB5B downregulation by miR-130a-3p inhibits cancer stem cell migration and invasion 6. Elevated RAB5B expression also correlates with insulin resistance in polycystic ovary syndrome, affecting PI3K/AKT and MAPK/ERK signaling pathways 7. Additionally, RAB5B upregulation promotes melanocore clustering in keratinocytes, relevant to melasma pathophysiology 8. These findings suggest RAB5B as a therapeutic target in multiple disease contexts.

Sources cited
1
RAB5B cycles between GDP-bound and GTP-bound forms to recruit effectors for vesicle dynamics; required for EEA1 recruitment and EGF/transferrin endocytosis
PMID: 16086013
2
RAB5B regulates vesicle formation, movement, tethering and fusion in early endocytic trafficking
PMID: 17562788
3
RAB5B is a 215-amino acid GTPase localizing to plasma membrane and early endosomes with GTP/GDP binding capacity
PMID: 1541686
4
RAB5B-CD109 interplay bypasses endosomal trafficking to promote extracellular vesicle packaging and perineural invasion in KRAS-mutant pancreatic cancer
PMID: 39488792
5
RAB5B expression varies across tumors with prognostic significance; inhibition reduces cell proliferation and migration
PMID: 40842984
6
Elevated RAB5B expression correlates with insulin resistance in PCOS; involved in PI3K/AKT/MAPK-ERK pathways affecting steroidogenesis
PMID: 39725769
7
miR-130a-3p downregulates RAB5B to inhibit breast cancer stem cell migration and invasion
PMID: 29746865
8
Tranexamic acid upregulates RAB5B to promote melanocore clustering in keratinocytes through endocytic pathway
PMID: 36779692
9
RAB5B is highly expressed in melanoma cells and regulates exosome formation supporting tumor metastasis
PMID: 22635005
Disease Associationsⓘ20
hypothyroidismOpen Targets
0.33Weak
type 1 diabetes mellitusOpen Targets
0.32Weak
neurodegenerative diseaseOpen Targets
0.32Weak
gastroesophageal reflux diseaseOpen Targets
0.30Weak
rheumatoid arthritisOpen Targets
0.30Weak
atopic eczemaOpen Targets
0.30Weak
asthmaOpen Targets
0.29Weak
childhood onset asthmaOpen Targets
0.27Weak
smoking cessationOpen Targets
0.26Weak
atopic asthmaOpen Targets
0.25Weak
sinusitisOpen Targets
0.24Weak
polycystic ovary syndromeOpen Targets
0.23Weak
autoimmune diseaseOpen Targets
0.18Weak
Nasal Cavity PolypOpen Targets
0.17Weak
basal cell carcinomaOpen Targets
0.15Weak
Nasal polyposisOpen Targets
0.10Suggestive
diabetic retinopathyOpen Targets
0.09Suggestive
alopecia areataOpen Targets
0.08Suggestive
narcolepsy-cataplexy syndromeOpen Targets
0.08Suggestive
attention deficit hyperactivity disorderOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RABEP1Protein interaction100%RABGEF1Protein interaction100%EEA1Protein interaction97%GAPVD1Protein interaction95%NBR1Protein interaction94%PIK3C3Protein interaction94%
Tissue Expression6 tissues
Brain
100%
Heart
93%
Ovary
60%
Lung
60%
Liver
48%
Bone Marrow
30%
Gene Interaction Network
Click a node to explore
RAB5BRABEP1RABGEF1EEA1GAPVD1NBR1PIK3C3
PROTEIN STRUCTURE
Preparing viewer…
PDB2HEI · 1.55 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.53Moderately Constrained
pLIⓘ
0.95Intolerant
Observed/Expected LoF0.30 [0.17–0.53]
RankingsWhere RAB5B stands among ~20K protein-coding genes
  • #4,613of 20,598
    Most Researched104 · top quartile
  • #3,348of 17,882
    Most Constrained (LOEUF)0.53 · top quartile
Genes detectedRAB5B
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Endosomal Trafficking Bypassed by the RAB5B-CD109 Interplay Promotes Axonogenesis in KRAS-Mutant Pancreatic Cancer.
PMID: 39488792
Adv Sci (Weinh) · 2024
1.00
2
Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET.
PMID: 22635005
Nat Med · 2012
0.90
3
PMID: 40842984
Front Immunol · 2025
0.80
4
Interplay between elevated RAB5B gene expression and insulin resistance among women with PCOS-insights from a case-control study.
PMID: 39725769
Endocrine · 2025
0.70
5
Identification and subcellular localization of human rab5b, a new member of the ras-related superfamily of GTPases.
PMID: 1541686
J Clin Invest · 1992
0.60