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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RAB21
RAB21, member RAS oncogene family
Chromosome 12 · 12q21.1
NCBI Gene: 23011Ensembl: ENSG00000080371.7HGNC: HGNC:18263UniProt: Q9UL25
122PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
focal adhesioncytoplasmic side of plasma membranevesicle membraneregulation of exocytosisneurodegenerative diseasesmall intestine neuroendocrine tumorneoplasmglioma
✦AI Summary

RAB21 is a small GTPase that regulates intracellular membrane trafficking and vesicle transport. As a member of the Rab family, it cycles between inactive GDP-bound and active GTP-bound states to control vesicle formation, movement, and fusion 1. RAB21 plays critical roles in integrin trafficking and recycling, which is essential for cell adhesion, migration, and cytokinesis 23. During cancer cell migration, RAB21 interacts with specific adaptors like Swiprosin-1 to facilitate integrin endocytosis through clathrin-independent pathways 2. In macrophages, RAB21 serves as a general regulator of surface protein expression, including Fc gamma receptors, affecting phagocytosis and cellular identity 4. RAB21 also functions in autophagy by regulating SNARE-mediated autophagosome-lysosome fusion and modulates Golgi trafficking of cargo receptors. Clinically, RAB21 has dual significance in disease: it acts as a tumor suppressor in renal cell carcinoma through EGFR pathway regulation 5, while functioning as an oncogene in gliomas where its knockdown induces apoptosis 6. RAB21 variants are associated with obesity 7 and the protein is degraded through both ubiquitin-proteasome and autophagy-lysosome pathways 8.

Sources cited
1
RAB21 is a small GTPase that cycles between GDP/GTP-bound states and regulates intracellular trafficking
PMID: 37369821
2
RAB21 interacts with Swiprosin-1 to facilitate integrin endocytosis in cancer cell migration
PMID: 34616024
3
RAB21 controls integrin recycling and supports breast cancer cell migration
PMID: 40669465
4
RAB21 is a general regulator of macrophage surface protein expression affecting phagocytosis
PMID: 40580479
5
RAB21 acts as tumor suppressor in renal cell carcinoma by regulating EGFR pathway
PMID: 37378422
6
RAB21 functions as oncogene in gliomas where knockdown induces apoptosis
PMID: 29270202
7
RAB21 variants are associated with obesity
PMID: 29273807
8
RAB21 protein is degraded by both ubiquitin-proteasome and autophagy-lysosome pathways
PMID: 35163051
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.47Moderate
small intestine neuroendocrine tumorOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.07Suggestive
gliomaOpen Targets
0.06Suggestive
posterior cortical atrophyOpen Targets
0.06Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.05Suggestive
breast cancerOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.05Suggestive
carcinoid syndromeOpen Targets
0.04Suggestive
ankyloglossiaOpen Targets
0.04Suggestive
small intestine carcinomaOpen Targets
0.04Suggestive
Alzheimer diseaseOpen Targets
0.04Suggestive
small intestine cancerOpen Targets
0.03Suggestive
hepatocellular carcinomaOpen Targets
0.03Suggestive
thyroid cancer, nonmedullary, 2Open Targets
0.03Suggestive
Abnormality of the immune systemOpen Targets
0.03Suggestive
malignant renal pelvis neoplasmOpen Targets
0.03Suggestive
gastrointestinal diseaseOpen Targets
0.03Suggestive
sialolithiasisOpen Targets
0.03Suggestive
kidney diseaseOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RABGEF1Protein interaction100%ANKRD27Protein interaction90%SBF2Protein interaction82%ITGB1Protein interaction82%GDI1Protein interaction77%GDI2Protein interaction72%
Tissue Expression6 tissues
Heart
100%
Brain
80%
Lung
41%
Bone Marrow
39%
Ovary
31%
Liver
30%
Gene Interaction Network
Click a node to explore
RAB21RABGEF1ANKRD27SBF2ITGB1GDI1GDI2
PROTEIN STRUCTURE
Preparing viewer…
PDB1Z08 · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.35LoF Tolerant
pLIⓘ
0.02Tolerant
Observed/Expected LoF0.69 [0.38–1.35]
RankingsWhere RAB21 stands among ~20K protein-coding genes
  • #3,863of 20,598
    Most Researched122 · top quartile
  • #14,149of 17,882
    Most Constrained (LOEUF)1.35
Genes detectedRAB21
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
MFN2 suppresses clear cell renal cell carcinoma progression by modulating mitochondria-dependent dephosphorylation of EGFR.
PMID: 37378422
Cancer Commun (Lond) · 2023
1.00
2
The Regulatory Mechanism of Rab21 in Human Diseases.
PMID: 37369821
Mol Neurobiol · 2023
0.90
3
Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.
PMID: 29273807
Nat Genet · 2018
0.80
4
Knockdown of Rab21 inhibits proliferation and induces apoptosis in human glioma cells.
PMID: 29270202
Cell Mol Biol Lett · 2017
0.70
5
Cargo-specific recruitment in clathrin- and dynamin-independent endocytosis.
PMID: 34616024
Nat Cell Biol · 2021
0.60