gene

VPS35

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about VPS35: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

428Connections

3Hypotheses

2Analyses

50Outgoing

50Incoming

1Experiments

4Debates

Summary

Gene profile: VPS35 — retromer complex component linked to PARK17 Parkinson's disease

View on Wiki →

No AI portrait yet

🧬 Gene Info

Gene Symbol	VPS35
Full Name	Vacuolar Protein Sorting 35 Homolog
Aliases	Vacuolar Protein Sorting 35
Protein Type	Protein
Function	Cargo Recognition: Binds to transmembrane cargo proteins containing cytoplasmic sorting motifs
Molecular Weight	91.6 kDa
Amino Acids	796 aa
Pathways	Wnt
UniProt ID	Search UniProt
GeneCards	VPS35
Human Protein Atlas	VPS35
Associated Diseases	Als, Alzheimer, Alzheimer's disease, Amyotrophic Lateral Sclerosis
Interactions	ABCA1, ABCA7, AD, AMYLOID, AND, APP
SciDEX Hypotheses	VPS35 retromer activation prevents endosomal tau t VPS35 Retromer Dysfunction Creates a GCase Traffic
KG Connections	427 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🔮 Predicted Structure: VPS35 — AlphaFold SEARCH Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (12)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    VPS35["VPS35"]
    VPS35 -->|"causes"| PD["PD"]
    VPS35 -->|"contributes to"| Parkinson["Parkinson"]
    VPS35 -->|"contributes to"| Als["Als"]
    VPS35 -->|"contributes to"| Inflammation["Inflammation"]
    VPS35 -->|"contributes to"| Neuroinflammation["Neuroinflammation"]
    VPS35 -->|"contributes to"| Ms["Ms"]
    VPS35 -->|"target for"| Aging["Aging"]
    PARK7["PARK7"] -->|"contributes to"| VPS35
    PINK1["PINK1"] -->|"contributes to"| VPS35
    GBA1["GBA1"] -->|"contributes to"| VPS35
    SNCA["SNCA"] -->|"contributes to"| VPS35
    LRRK2["LRRK2"] -->|"contributes to"| VPS35
    PRKN["PRKN"] -->|"contributes to"| VPS35
    AGING["AGING"] -->|"target for"| VPS35
    FLAVONOIDS["FLAVONOIDS"] -->|"target for"| VPS35
    MITOCHONDRIAL_DYSFUNCTION["MITOCHONDRIAL DYSFUNCTION"] -->|"target for"| VPS35
    DRP1["DRP1"] -->|"interacts"| VPS35

Outgoing (190)

Target	Relation	Type	Str
Parkinson's Disease	causes	disease	0.95
p.D620N mutation	causes	mechanism	0.95
Parkinson's disease	associated_with	disease	0.95
Retinal Degeneration	contributes_to	phenotype	0.95
Late Endosomal Trafficking	regulates	process	0.95
Retromer-Dependent Endosomal Trafficking	involved_in	process	0.95
TAU	regulates	protein	0.95
Retromer Complex	component_of	pathway	0.95
Parkinson's Disease	associated_with	disease	0.95
APLP1	regulates	protein	0.90
Presynaptic Trafficking	regulates	process	0.90
CHL1	regulates	protein	0.90
Endo-Lysosome System	regulates	organelle	0.90
TRPL	regulates	protein	0.90
PINK1/parkin-mediated mitophagy	inhibits	pathway	0.90
Alzheimer's Disease	associated_with	disease	0.90
Amyotrophic Lateral Sclerosis	associated_with	disease	0.90
HSC70	interacts_with	protein	0.90
Α-SYNUCLEIN	associated_with	protein	0.90
Inflammatory Cell Death	regulates	process	0.85
TAU PROTEIN	regulates	protein	0.85
DAT	interacts_with	protein	0.85
Protein Transport	mediates	process	0.85
SYNAPTIC GLUTAMATE RECEPTORS	regulates	receptor	0.85
Amyloid Precursor Protein Cleavage	regulates	process	0.85
GLUA1	regulates	receptor	0.85
Phosphorylated Tau	downregulates	entity	0.85
LRRK2	associated_with	protein	0.85
MAPL-Induced Pyroptosis	regulates	process	0.85
LRRK2 kinase activity	upregulates	mechanism	0.85
Ubiquitin-Proteasome System	regulates	process	0.80
autophagy pathway	participates_in	pathway	0.80
Microglial Phenotype	regulates	phenotype	0.80
Mapl-Induced Pyroptosis	regulates	process	0.80
Parkinson	associated_with	disease	0.75
Parkinson'S Disease	associated_with	disease	0.75
PD	causes	disease	0.72
BST-2	regulates	protein	0.70
Aging	therapeutic_target	disease	0.65
GLUTAMATE	transports	phenotype	0.65
NEURONS	regulates	cell_type	0.65
Als	therapeutic_target	disease	0.65
AUTOPHAGY	treats	phenotype	0.65
Parkinson	activates	disease	0.65
Als	activates	disease	0.65
Cancer	activates	disease	0.65
Ms	therapeutic_target	disease	0.65
Parkinson	causes	disease	0.65
Inflammation	causes	disease	0.65
Neuroinflammation	causes	disease	0.65

Incoming (238)

Source	Relation	Type	Str
entities-snx5	associated_with	wiki	0.00
SYNJ1	interacts_with	gene	0.95
FAF2	interacts_with	entity	0.85
LDLR	activates	gene	0.70
TFEB	interacts_with	gene	0.70
LAMP1	activates	gene	0.70
TAU	activates	gene	0.70
SQSTM1	activates	gene	0.70
PSEN1	activates	gene	0.70
NRF2	activates	gene	0.70
FBXO7	targets	gene	0.70
MACROPHAGE	inhibits	cell_type	0.70
STING	associated_with	gene	0.70
DOPAMINERGIC	associated_with	cell_type	0.70
PICALM	associated_with	gene	0.70
NEURONS	activates	cell_type	0.70
APP	mediates	gene	0.70
PARKINSON'S DISEASE	associated_with	gene	0.70
PARKINSON	associated_with	gene	0.70
LRRK2	regulates	gene	0.65
NEURON	degrades	cell_type	0.65
PYROPTOSIS	activates	gene	0.60
MTDNA	regulates	gene	0.60
CANCER	regulates	gene	0.60
MITOCHONDRIAL DNA	regulates	gene	0.60
PARKINSON'S DISEASE	activates	gene	0.60
MAPL	inhibits	gene	0.60
NEURON	activates	cell_type	0.60
PD	co_discussed	gene	0.60
PD	causes	gene	0.60
AUTOPHAGY	activates	pathway	0.60
PD	associated_with	gene	0.60
PD	mediates	gene	0.60
TREM2	degrades	gene	0.60
TREM2	activates	gene	0.60
AD	interacts_with	gene	0.60
TREM2	interacts_with	gene	0.60
AD	regulates	gene	0.60
MICROGLIA	regulates	cell_type	0.60
TREM2	regulates	gene	0.60
ALZHEIMER'S DISEASE	regulates	disease	0.60
PARKINSON'S DISEASE	regulates	disease	0.60
AND	activates	gene	0.60
GENES	associated_with	gene	0.60
PARKIN	associated_with	gene	0.60
DJ1	associated_with	gene	0.60
ATG5	regulates	gene	0.60
CGAS	regulates	gene	0.60
LYSOSOME	therapeutic_target	gene	0.60
DNA	regulates	gene	0.60

Targeting Hypotheses (3)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
VPS35 retromer activation prevents endosomal tau templating	0.740	neurodegeneration	Which tau propagation mechanism predomin
VPS35 Retromer Dysfunction Creates a GCase Trafficking Bottl	0.700	neurodegeneration	-
VPS35 Retromer Restoration to Rescue Endosomal Protein Traff	0.525	proteomics	Quantitative proteomics of the aging syn

Mentioning Analyses (2)

Scientific analyses that reference this entity

Quantitative proteomics of the aging synapse: protein turnover and aggregation i

proteomics | 2026-04-16 | 16 hypotheses Top: 0.591

What molecular mechanisms enable microglia to neutralize OxPC-mediated neurodege

neuroinflammation | 2026-04-13 | 2 hypotheses Top: 0.453

Experiments (1)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Evidence regarding pain in VPS35 pathogenic variants is limited and in	genetic_association	Parkinson's disease	0.500	0.00	human	extracted	N/A

Related Papers (8)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
Extracellular vesicles from IPFP-MSCs trigger osteoarthritis by transferring mtD [PMID:41480405]	Li S, Yan Z, Zhi X, Zheng W, Zhang Z et	Bioact Mater	2026
Comprehensive multi-omics analysis and experimental validation indicate that VPS [PMID:41531939]	Wan D, Qi Y, Kang Y, Liang F, Wang Q et	RSC Med Chem	2026
Integrated Bioinformatics Analysis of Screen Mitochondrial Autophagy-Related Cor [PMID:41731906]	Gao Z, Wang Y, Ren Y, Lyu J	J Neurochem	2026
VPS35 Deficiency Markedly Reduces the Proliferation of HEK293 Cells. [PMID:41751560]	Lee S, Park S, Bang H, Kim SU, Park YH e	Genes (Basel)	2026
N-acetyl-l-leucine lowers α-synuclein levels and improves synaptic function in P [PMID:41766663]	Song P, Chen C, Franchini R, Duong B, Wa	J Clin Invest	2026
The VPS35 protein and the role of its impairments in mitochondrial dysfunction i [PMID:41841708]	Buneeva OA, Medvedev AE	Biomed Khim	2026
Vps35 p. D620N causes Lrrk2 kinase hyperactivity, chronic microglial activation [PMID:41846978]	Deng IB, Bu M, Follett J, Sharp R, Mamai	bioRxiv	2026
Lack of Cerebrospinal Fluid α-Synuclein Seeding in VPS35 D620N- and LRRK2 Y1699C [PMID:41912440]	Santinelli L, Pratuseviciute N, Lange LM	Mov Disord	2026

Debates (4)

Multi-agent debates referencing this entity

How does synaptic protein turnover change with age and neurodegeneration, and wh

closed · Rounds: 4 · Score: 0.50 · 2026-04-18

The abstract shows microglia ameliorate OxPC toxicity to neurons and oligodendro

closed · Rounds: 4 · Score: 0.68 · 2026-04-14

The abstract shows microglia ameliorate OxPC toxicity to neurons and oligodendro

closed · Rounds: 4 · Score: 0.62 · 2026-04-14

The abstract shows microglia ameliorate OxPC toxicity to neurons and oligodendro

closed · Rounds: 4 · Score: 0.92 · 2026-04-14

Related Research

Hypotheses and analyses mentioning VPS35 in their description or question text

No additional research found

VPS35

Understanding Entity Pages

Summary

Wiki Pages (12)

VPS35 — Vacuolar Protein Sorting 35 Homolog

VPS35 Retromer Dysfunction Parkinson's Disease Causal Chain

VPS35 Retromer Stabilizer for Lysosomal Rescue

VPS35/Retromer Pathway in Parkinson's Disease

VPS35 Protein

VPS35 Pathway in Parkinson's Disease

VPS35/Retromer Stabilizers for Parkinson's Disease

VPS35 Retromer Pharmacological Chaperone

VPS35/Retromer Stabilizers for Parkinson's Disease

VPS35 Retromer Targeting Therapies

VPS35 Mutant Neurons

VPS35 Protein

Pathway Diagram

Outgoing (190)

Incoming (238)

Targeting Hypotheses (3)

Mentioning Analyses (2)

Quantitative proteomics of the aging synapse: protein turnover and aggregation i

What molecular mechanisms enable microglia to neutralize OxPC-mediated neurodege

Experiments (1)

Related Papers (8)

Debates (4)

How does synaptic protein turnover change with age and neurodegeneration, and wh

The abstract shows microglia ameliorate OxPC toxicity to neurons and oligodendro

The abstract shows microglia ameliorate OxPC toxicity to neurons and oligodendro

The abstract shows microglia ameliorate OxPC toxicity to neurons and oligodendro

Related Research