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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RAB35
RAB35, member RAS oncogene family
Chromosome 12 · 12q24.23
NCBI Gene: 11021Ensembl: ENSG00000111737.13HGNC: HGNC:9774UniProt: Q15286
127PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
clathrin-coated endocytic vesicleintercellular bridgeclathrin-coated pitcell projection membraneneurodegenerative diseaseearly-onset non-syndromic cataractcystTotal congenital cataract
✦AI Summary

RAB35 is a small GTPase that serves as a master regulator of membrane trafficking with diverse cellular functions. As a member of the Rab family, RAB35 cycles between inactive GDP-bound and active GTP-bound states to recruit specific downstream effectors 1. The protein plays essential roles in endocytic recycling, functioning as a rate-limiting regulator of the fast recycling pathway back to the plasma membrane 2. During cytokinesis, RAB35 is required for intercellular bridge stability and abscission, working alongside RAB11 to orchestrate the completion of cell division 3. RAB35 serves as a central regulator of phosphoinositides and F-actin both on endosomes and at the plasma membrane, explaining its involvement in diverse processes including phagocytosis, cell migration, and neurite outgrowth 2. In neurons, RAB35 coordinates synaptic vesicle trafficking and turnover, with its signaling network being critical for synaptic protein homeostasis 4. The protein has emerged as clinically significant, with activating mutations conferring oncogenic properties in cancer 5. Additionally, RAB35 can be phosphorylated by LRRK2 kinase, linking it to Parkinson's disease pathways through lysosomal tubulation processes 6. Mutations in RAB35 regulatory proteins are associated with neurologic and neurodegenerative diseases 4.

Sources cited
1
RAB35 cycles between inactive GDP-bound and active GTP-bound states to recruit downstream effectors
PMID: 30905672
2
RAB35 is a rate-limiting regulator of fast recycling pathway and central regulator of phosphoinositides and F-actin
PMID: 27329675
3
RAB35 works with RAB11 to orchestrate completion of cell division during cytokinesis
PMID: 40877912
4
RAB35 coordinates synaptic vesicle trafficking and mutations in regulatory proteins cause neurologic diseases
PMID: 28129039
5
Activating mutations confer RAB35 with oncogenic properties in cancer
PMID: 29314576
6
RAB35 can be phosphorylated by LRRK2 kinase in lysosomal tubulation processes relevant to Parkinson's disease
PMID: 33177079
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.42Moderate
early-onset non-syndromic cataractOpen Targets
0.11Weak
cystOpen Targets
0.10Suggestive
Total congenital cataractOpen Targets
0.10Suggestive
Partial congenital cataractOpen Targets
0.10Suggestive
Parkinson diseaseOpen Targets
0.10Suggestive
Cataract-microcornea syndromeOpen Targets
0.09Suggestive
early-onset nuclear cataractOpen Targets
0.09Suggestive
early-onset zonular cataractOpen Targets
0.09Suggestive
isolated ectopia lentisOpen Targets
0.08Suggestive
hereditary hyperferritinemia with congenital cataractsOpen Targets
0.08Suggestive
pulverulent cataractOpen Targets
0.08Suggestive
infectionOpen Targets
0.08Suggestive
Posterior polar cataractOpen Targets
0.08Suggestive
Cataract with Y-shaped suture opacitiesOpen Targets
0.07Suggestive
cataract 35Open Targets
0.07Suggestive
cataract 13 with adult I phenotypeOpen Targets
0.07Suggestive
cataract 38Open Targets
0.07Suggestive
Anterior polar cataractOpen Targets
0.07Suggestive
Cochleosaccular degeneration - cataractOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DENND1BProtein interaction100%DENND1AProtein interaction100%TBC1D10AProtein interaction99%DENND1CProtein interaction98%RUSC2Protein interaction96%MADDProtein interaction96%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
94%
Ovary
67%
Brain
65%
Heart
63%
Liver
60%
Gene Interaction Network
Click a node to explore
RAB35DENND1BDENND1ATBC1D10ADENND1CRUSC2MADD
PROTEIN STRUCTURE
Preparing viewer…
PDB6IF3 · 1.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.33Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.14 [0.07–0.33]
RankingsWhere RAB35 stands among ~20K protein-coding genes
  • #3,700of 20,598
    Most Researched127 · top quartile
  • #1,370of 17,882
    Most Constrained (LOEUF)0.33 · top 10%
Genes detectedRAB35
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
LRRK2 mediates tubulation and vesicle sorting from lysosomes.
PMID: 33177079
Sci Adv · 2020
1.00
2
Rab35 GTPase and cancer: Linking membrane trafficking to tumorigenesis.
PMID: 29314576
Traffic · 2018
0.90
3
Rab35 GTPase: A Central Regulator of Phosphoinositides and F-actin in Endocytic Recycling and Beyond.
PMID: 27329675
Traffic · 2016
0.80
4
Coordination of synaptic vesicle trafficking and turnover by the Rab35 signaling network.
PMID: 28129039
Small GTPases · 2019
0.70
5
Post-translational targeting of Rab35 by the effector IcsB of Shigella determines intracellular bacterial niche formation.
PMID: 38568808
Cell Rep · 2024
0.60