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25 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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RAB5C
RAB5C, member RAS oncogene family
Chromosome 17 · 17q21.2
NCBI Gene: 5878Ensembl: ENSG00000108774.16HGNC: HGNC:9785UniProt: P51148
176PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GTPase activityGDP bindinglysosomal membraneendosomeNeurodevelopmental disorderhypothyroidismmyxedemagenetic disorder
✦AI Summary

RAB5C is a small GTPase that belongs to the Rab family and serves as a key regulator of early endocytic trafficking and membrane vesicle dynamics. The protein cycles between inactive GDP-bound and active GTP-bound forms, with the active state recruiting downstream effectors responsible for vesicle formation, movement, and fusion 1. RAB5C is essential for EEA1 recruitment to early endosomes and facilitates endocytosis and trafficking of receptors including EGF and transferrin through early endosomes 1. Beyond endocytosis, RAB5C plays important roles in autophagy regulation by interacting with Beclin1 to upregulate LC3-II expression and promote autophagic processes 2. The protein also participates in lysosomal degradation pathways, directing proteins like ACC1 to lysosomes via P62-dependent selective autophagy 3. Disease relevance includes its involvement in hepatocellular carcinoma progression through ferroptosis suppression 3, angiogenesis regulation by preventing VEGFR2 degradation 4, and viral replication promotion 2. Clinically, de novo missense variants in RAB5C cause a neurodevelopmental disorder characterized by macrocephaly and developmental delay through dominant negative mechanisms that disrupt endocytic pathway function 1.

Sources cited
1
RAB5C cycles between GDP/GTP-bound forms, is essential for EEA1 recruitment and endocytosis, and missense variants cause neurodevelopmental disorders with macrocephaly
PMID: 37552066
2
RAB5C promotes autophagy by interacting with Beclin1 and upregulating LC3-II expression
PMID: 38242290
3
RAB5C directs ACC1 to lysosomes via P62-dependent autophagy and is involved in hepatocellular carcinoma ferroptosis suppression
PMID: 39779666
4
RAB5C prevents VEGFR2 degradation and regulates angiogenesis by maintaining receptor signaling
PMID: 33983539
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
Neurodevelopmental disorderOpen Targets
0.51Moderate
hypothyroidismOpen Targets
0.37Weak
myxedemaOpen Targets
0.32Weak
genetic disorderOpen Targets
0.19Weak
macrocephaly-developmental delay syndromeOpen Targets
0.12Weak
autoimmune thyroid diseaseOpen Targets
0.12Weak
ovarian dysfunctionOpen Targets
0.11Weak
autoimmune diseaseOpen Targets
0.10Weak
coronary artery diseaseOpen Targets
0.09Suggestive
VitiligoOpen Targets
0.09Suggestive
thyroid diseaseOpen Targets
0.07Suggestive
Hashimoto's thyroiditisOpen Targets
0.04Suggestive
Combined hyperlipidemiaOpen Targets
0.04Suggestive
hypertriglyceridemia 2Open Targets
0.04Suggestive
pancreatic triacylglycerol lipase deficiencyOpen Targets
0.03Suggestive
familial hypercholesterolemiaOpen Targets
0.03Suggestive
homozygous familial hypercholesterolemiaOpen Targets
0.03Suggestive
Respiratory Syncytial Virus InfectionOpen Targets
0.03Suggestive
congenital enteropathy due to enteropeptidase deficiencyOpen Targets
0.03Suggestive
hepatocellular carcinomaOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CHMProtein interaction99%CHMLProtein interaction99%GDI1Protein interaction99%GDI2Protein interaction99%RABGGTAProtein interaction99%RIN1Protein interaction99%
Tissue Expression6 tissues
Brain
100%
Lung
98%
Bone Marrow
93%
Liver
76%
Ovary
56%
Heart
34%
Gene Interaction Network
Click a node to explore
RAB5CCHMCHMLGDI1GDI2RABGGTARIN1
PROTEIN STRUCTURE
Preparing viewer…
PDB4KYI · 3.08 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.41Moderately Constrained
pLIⓘ
0.99Intolerant
Observed/Expected LoF0.16 [0.07–0.41]
RankingsWhere RAB5C stands among ~20K protein-coding genes
  • #2,488of 20,598
    Most Researched176 · top quartile
  • #2,104of 17,882
    Most Constrained (LOEUF)0.41 · top quartile
Genes detectedRAB5C
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
S100P is a ferroptosis suppressor to facilitate hepatocellular carcinoma development by rewiring lipid metabolism.
PMID: 39779666
Nat Commun · 2025
1.00
2
Defining mitochondrial protein functions through deep multiomic profiling.
PMID: 35614220
Nature · 2022
0.90
3
Macrocephaly and developmental delay caused by missense variants in RAB5C.
PMID: 37552066
Hum Mol Genet · 2023
0.80
4
RAB5A Promotes Active Fluid Wetting by Reprogramming Breast Cancer Spheroid Mechanics.
PMID: 40712149
Adv Sci (Weinh) · 2025
0.76
5
Endogenous interactomes of MFN1 and MFN2 provide novel insights into interorganelle communication and autophagy.
PMID: 39675054
Autophagy · 2025
0.70