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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RAB4A
RAB4A, member RAS oncogene family
Chromosome 1 · 1q42.13
NCBI Gene: 5867Ensembl: ENSG00000168118.12HGNC: HGNC:9781UniProt: A0A087WYT5
113PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
perinuclear region of cytoplasmGTP bindingGTPase activityvesicleliver diseasepneumonitissubarachnoid hemorrhagebenign neoplasm of adrenal gland
✦AI Summary

RAB4A is a small GTPase that serves as a key regulator of intracellular membrane trafficking, particularly in endocytic recycling pathways 1. The protein cycles between inactive GDP-bound and active GTP-bound conformations to recruit downstream effectors responsible for vesicle formation, movement, and fusion 1. RAB4A demonstrates atypical GTPase kinetics with rapid GTP exchange and slow hydrolysis rates, suggesting it can self-activate and persist in an activated state 2. The protein regulates fast recycling from early endosomes and organizes endosomal domains for cargo sorting to lysosome-related organelles 34. RAB4A forms endosomal complexes with adaptor AP-3, effector rabenosyn-5, and motor KIF3 to coordinate cargo segregation 4. Clinically, RAB4A has significant cancer relevance, functioning as a master regulator of cancer stem cell properties through the NUMB-NOTCH signaling pathway 5. It controls epithelial-to-mesenchymal transition via RAC1 activation and regulates integrin β3 recycling essential for cell migration and metastasis 67. RAB4A's carboxylmethylation by ICMT is critical for its activation and proper endosomal localization 7. These findings establish RAB4A as both a fundamental trafficking regulator and potential therapeutic target for metastatic cancer.

Sources cited
1
RAB4A cycles between GDP/GTP-bound forms and regulates endocytic recycling
PMID: 15907487
2
RAB4A regulates fast recycling from early endosomes in cancer cell migration
PMID: 37232246
3
RAB4A acts as master regulator of cancer stem cells via NUMB-NOTCH signaling
PMID: 39463384
4
RAB4A controls epithelial-to-mesenchymal transition through RAC1 activation
PMID: 36307864
5
RAB4A shows atypical GTPase kinetics with rapid exchange and slow hydrolysis
PMID: 32707235
6
RAB4A organizes endosomal domains and forms complexes with AP-3, rabenosyn-5, and KIF3
PMID: 30154210
7
ICMT-mediated carboxylmethylation is essential for RAB4A-dependent integrin β3 recycling and metastasis
PMID: 28604748
Disease Associationsⓘ20
liver diseaseOpen Targets
0.29Weak
pneumonitisOpen Targets
0.29Weak
subarachnoid hemorrhageOpen Targets
0.26Weak
benign neoplasm of adrenal glandOpen Targets
0.25Weak
schizophreniaOpen Targets
0.21Weak
Abruptio PlacentaeOpen Targets
0.19Weak
placental retentionOpen Targets
0.18Weak
systemic lupus erythematosusOpen Targets
0.10Suggestive
cancerOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.09Suggestive
gastric cancerOpen Targets
0.08Suggestive
Huntington diseaseOpen Targets
0.07Suggestive
Romano-Ward syndromeOpen Targets
0.07Suggestive
Familial short QT syndromeOpen Targets
0.07Suggestive
Familial progressive cardiac conduction defectOpen Targets
0.07Suggestive
familial atrial fibrillationOpen Targets
0.07Suggestive
Brugada syndromeOpen Targets
0.06Suggestive
catecholaminergic polymorphic ventricular tachycardiaOpen Targets
0.06Suggestive
Arrhythmogenic right ventricular dysplasiaOpen Targets
0.06Suggestive
neuroendocrine neoplasmOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
STX4Protein interaction100%EEA1Protein interaction100%RBSNProtein interaction100%ARF6Protein interaction99%RAB11FIP3Protein interaction95%RAB11FIP1Protein interaction93%
Tissue Expression6 tissues
Heart
100%
Brain
56%
Liver
42%
Ovary
25%
Bone Marrow
19%
Lung
19%
Gene Interaction Network
Click a node to explore
RAB4ASTX4EEA1RBSNARF6RAB11FIP3RAB11FIP1
PROTEIN STRUCTURE
Preparing viewer…
PDB2BME · 1.57 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.83LoF Tolerant
pLIⓘ
0.09Tolerant
Observed/Expected LoF0.48 [0.29–0.83]
RankingsWhere RAB4A stands among ~20K protein-coding genes
  • #4,200of 20,598
    Most Researched113 · top quartile
  • #7,122of 17,882
    Most Constrained (LOEUF)0.83
Genes detectedRAB4A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
High resolution crystal structures of human Rab4a in its active and inactive conformations.
PMID: 15907487
FEBS Lett · 2005
1.00
2
Proximity labelling identifies pro-migratory endocytic recycling cargo and machinery of the Rab4 and Rab11 families.
PMID: 37232246
J Cell Sci · 2023
0.90
3
RAB4A is a master regulator of cancer cell stemness upstream of NUMB-NOTCH signaling.
PMID: 39463384
Cell Death Dis · 2024
0.80
4
RAB4A GTPase regulates epithelial-to-mesenchymal transition by modulating RAC1 activation.
PMID: 36307864
Breast Cancer Res · 2022
0.70
5
In-depth NMR characterization of Rab4a structure, nucleotide exchange and hydrolysis kinetics reveals an atypical GTPase profile.
PMID: 32707235
J Struct Biol · 2020
0.60