mechanism 1,643 words KG: ent-gene-96ed1757 2026-04-01
evidence:strongmechanismmechanismspublishedcausal-chainsendosomal-traffickinglysosomal-dysfunctionparkinsons
Contents

DNAJC13→Endosomal Dysfunction→PD Causal Chain

🔬 Protein Info
Gene Symbolent-gene-96ed1757
Chromosome3q28
Subcellular Localization, reducing its endosomal enrichment
J domainPositions 1-70 — recruits Hsc70 (HSPA8) via HPD motif
N-terminal domainPositions 71-450 — protein-protein interactions
SDF domainPositions 1400-1550 — sorting nexin interaction
C-terminal regionPositions 1551-2328 — retromer and WASH complex interactions
Reduced Hsc70 recruitmentThe N855S substitution in the J domain impairs the interaction with Hsc70, reducing the availability of chaperone activity on endosomal membranes
Disrupted membrane associationSome mutations alter the protein's subcellular localization, reducing its endosomal enrichment
Impaired protein-protein interactionsMutations in the NPH and C-terminal domains disrupt interactions with retromer, WASH, and sorting nexins
KG Connections2 knowledge graph edges
DatabasesGeneCardsUniProtNCBI GeneHPASTRING

Knowledge Graph

Related Hypotheses (9)

Targeted Butyrate Supplementation for Microglial Phenotype M
Score: 0.56
Extracellular Vesicle Biogenesis Modulation
Score: 0.34
Cell-Type Specific TFEB Modulation
Score: 0.48
Lysosomal Enzyme Trafficking Correction
Score: 0.49
TFAM overexpression creates mitochondrial donor-recipient gr
Score: 0.47

Related Analyses (30)

Autophagy-lysosome pathway convergence across neurodegenerat
neurodegeneration · archived
Lipid raft composition changes in synaptic neurodegeneration
neurodegeneration · completed
Mitochondrial transfer between astrocytes and neurons
neurodegeneration · archived
Selective vulnerability of entorhinal cortex layer II neuron
neurodegeneration · archived
4R-tau strain-specific spreading patterns in PSP vs CBD
neurodegeneration · archived

Related Experiments (5)

Cytochrome Therapeutics
clinical · proposed · Score: 0.40
Macroautophagy Dysfunction in PD - Experiment Design
clinical · proposed · Score: 0.40
Trehalose-induced lysosomal changes and TFEB activation
exploratory · proposed · Score: 0.90
Trehalose-induced lysosomal membrane permeabilization and TF
exploratory · proposed · Score: 0.90
Functional validation of trehalose effects on misfolded prot
exploratory · proposed · Score: 0.85

Knowledge Graph (2 edges)

ent-gene-96ed1757 data_in benchmark_ot_ad_answer_key:DNAJC13
benchmark_ot_ad_answer_key:DNAJC13 data_in ent-gene-96ed1757