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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RAB8A
RAB8A, member RAS oncogene family
Chromosome 19 · 19p13.11
NCBI Gene: 4218Ensembl: ENSG00000167461.13HGNC: HGNC:7007UniProt: P61006
225PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneOncogeneTransporter
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
myosin V bindingcentrosomemidbodyregulation of autophagyesophageal cancercongenital diarrhea 5 with tufting enteropathyIntestinal epithelial dysplasianon-small cell lung carcinoma
✦AI Summary

RAB8A is a small GTPase functioning as a master regulator of intracellular membrane trafficking and polarized vesicular transport 1. The protein cycles between inactive GDP-bound and active GTP-bound states, recruiting downstream effectors that mediate vesicle formation, movement, and fusion 1. RAB8A promotes apical membrane formation and lumenogenesis in epithelial cells through the exocyst complex and associated proteins 1, regulates Golgi morphology 2, and participates in epithelial cell polarization with MYO5B and RAB11A 3. The protein also coordinates cilium membrane trafficking and ciliogenesis 45. Mechanistically, RAB8A functions as a mitochondrial receptor binding PLIN5 on lipid droplets, facilitating energy-dependent fatty acid mobilization during exercise via AMPK-mediated activation 6. LRRK2 phosphorylation stabilizes RAB8A on stressed lysosomes where it suppresses stress-induced enlargement through effector proteins 7. The C9orf72-SMCR8 complex negatively regulates RAB8A-dependent primary ciliogenesis by functioning as a RAB8A GTPase-activating protein 89. Disease relevance is substantial: LRRK2-mediated RAB8A phosphorylation contributes to Parkinson's disease pathology through altered lysosomal pH and α-synuclein accumulation 10, defective endolysosomal repair 11, and iron mishandling in microglia 12. C9orf72 mutations causing ALS/FTD lead to ciliary abnormalities via RAB8A dysregulation 8. Additionally, GPR137-RAB8A activation promotes ovarian cancer progression through Hedgehog pathway activation 13.

Sources cited
1
RAB8A is a small GTPase functioning as a master regulator of intracellular membrane trafficking and polarized vesicular transport .
PMID: 20890297
2
RAB8A promotes apical membrane formation and lumenogenesis in epithelial cells through the exocyst complex and associated proteins , regulates Golgi morphology , and participates in epithelial cell polarization with MYO5B and RAB11A .
PMID: 26209634
3
RAB8A promotes apical membrane formation and lumenogenesis in epithelial cells through the exocyst complex and associated proteins , regulates Golgi morphology , and participates in epithelial cell polarization with MYO5B and RAB11A .
PMID: 21282656
4
Mechanistically, RAB8A functions as a mitochondrial receptor binding PLIN5 on lipid droplets, facilitating energy-dependent fatty acid mobilization during exercise via AMPK-mediated activation .
PMID: 36800997
5
LRRK2 phosphorylation stabilizes RAB8A on stressed lysosomes where it suppresses stress-induced enlargement through effector proteins .
PMID: 30209220
6
Disease relevance is substantial: LRRK2-mediated RAB8A phosphorylation contributes to Parkinson's disease pathology through altered lysosomal pH and α-synuclein accumulation , defective endolysosomal repair , and iron mishandling in microglia .
PMID: 38307024
7
Disease relevance is substantial: LRRK2-mediated RAB8A phosphorylation contributes to Parkinson's disease pathology through altered lysosomal pH and α-synuclein accumulation , defective endolysosomal repair , and iron mishandling in microglia .
PMID: 32643832
8
Disease relevance is substantial: LRRK2-mediated RAB8A phosphorylation contributes to Parkinson's disease pathology through altered lysosomal pH and α-synuclein accumulation , defective endolysosomal repair , and iron mishandling in microglia .
PMID: 34914695
9
The C9orf72-SMCR8 complex negatively regulates RAB8A-dependent primary ciliogenesis by functioning as a RAB8A GTPase-activating protein , .
PMID: 38064514
10
Additionally, GPR137-RAB8A activation promotes ovarian cancer progression through Hedgehog pathway activation .
PMID: 39856733
Disease Associationsⓘ20
esophageal cancerOpen Targets
0.08Suggestive
congenital diarrhea 5 with tufting enteropathyOpen Targets
0.07Suggestive
Intestinal epithelial dysplasiaOpen Targets
0.07Suggestive
non-small cell lung carcinomaOpen Targets
0.07Suggestive
Diarrhea, InfantileOpen Targets
0.07Suggestive
lactose intolerance adult typeOpen Targets
0.06Suggestive
acute respiratory distress syndromeOpen Targets
0.06Suggestive
microvillus inclusion diseaseOpen Targets
0.06Suggestive
DiarrheaOpen Targets
0.06Suggestive
inflammatory bowel disease 30Open Targets
0.06Suggestive
Congenital malabsorptive diarrhea due to paucity of enteroendocrine cellsOpen Targets
0.06Suggestive
congenital sucrase-isomaltase deficiencyOpen Targets
0.06Suggestive
chronic diarrhea due to glucoamylase deficiencyOpen Targets
0.05Suggestive
Congenital chronic diarrhea with protein-losing enteropathyOpen Targets
0.05Suggestive
congenital diarrhea 7 with exudative enteropathyOpen Targets
0.05Suggestive
congenital short bowel syndromeOpen Targets
0.05Suggestive
congenital short bowel syndrome, autosomal recessiveOpen Targets
0.05Suggestive
Genetic intractable diarrhea of infancyOpen Targets
0.05Suggestive
Hirschsprung diseaseOpen Targets
0.05Suggestive
bile acid malabsorption, primary, 1Open Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EXOC6Protein interaction100%C9orf72Protein interaction100%OCRLProtein interaction100%OPTNProtein interaction99%MICALL2Protein interaction99%CEP290Protein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
78%
Brain
72%
Lung
58%
Ovary
44%
Heart
25%
Gene Interaction Network
Click a node to explore
RAB8AEXOC6C9orf72OCRLOPTNMICALL2CEP290
PROTEIN STRUCTURE
Preparing viewer…
PDB4LHW · 1.55 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.34Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.15 [0.07–0.34]
RankingsWhere RAB8A stands among ~20K protein-coding genes
  • #1,811of 20,598
    Most Researched225 · top 10%
  • #1,461of 17,882
    Most Constrained (LOEUF)0.34 · top 10%
Genes detectedRAB8A
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Rab8a as a mitochondrial receptor for lipid droplets in skeletal muscle.
PMID: 36800997
Dev Cell · 2023
1.00
2
The LRRK2 kinase substrates RAB8a and RAB10 contribute complementary but distinct disease-relevant phenotypes in human neurons.
PMID: 38307024
Stem Cell Reports · 2024
0.90
3
Rab11-Rab8 cascade dynamics in primary cilia and membrane tubules.
PMID: 39520683
Cell Rep · 2024
0.80
4
ALS-linked C9orf72-SMCR8 complex is a negative regulator of primary ciliogenesis.
PMID: 38064514
Proc Natl Acad Sci U S A · 2023
0.80
5
Kinome screening identifies integrated stress response kinase EIF2AK1/HRI as a negative regulator of PINK1 mitophagy signaling.
PMID: 40344059
Sci Adv · 2025
0.70