disease 2,218 words KG: ent-dise-f557a6b1
Contents

vcp-multisystem-proteinopathy

Disease Info
Typical OnsetProgressive limb-girdle weakness, initially affecting the hip girdle and quadriceps
N-terminal domain (N-domain)Mediates interactions with cofactors and adaptors (e.g., p47, Ufd1-Npl4, UBXD1)
D1 ATPase domainFirst AAA+ domain; primarily involved in hexamer assembly
D1-D2 linkerConnects the two ATPase domains
D2 ATPase domainPrimary source of ATP hydrolysis and mechanical force generation
C-terminal tailContains regulatory phosphorylation sites
R155HThe most common mutation, accounting for ~50% of reported families
R155C, R155P, R155SOther substitutions at the R155 hotspot
R191QSecond most common mutation
A232ELocated in the D1-D2 linker
Rare mutationsIn the D1 and D2 domains (e.g., N387H, A439S, D592N)
Myopathy~90% penetrance by age 50
DatabasesOMIMOrphanetClinicalTrialsPubMed

Knowledge Graph

Related Hypotheses (10)

Bacterial Enzyme-Mediated Dopamine Precursor Synthesis
Score: 0.36
VCP-Mediated Autophagy Enhancement
Score: 0.41
APOE-Dependent Autophagy Restoration
Score: 0.61
Phase-Separated Organelle Targeting
Score: 0.52
Heat Shock Protein 70 Disaggregase Amplification
Score: 0.51

Related Analyses (5)

What are the mechanisms by which gut microbiome dysbiosis in
neurodegeneration · archived
Tau propagation mechanisms and therapeutic interception poin
neurodegeneration · archived
Autophagy-lysosome pathway convergence across neurodegenerat
neurodegeneration · archived
Protein aggregation cross-seeding across neurodegenerative d
neurodegeneration · archived
Metabolic reprogramming in neurodegenerative disease
neurodegeneration · completed

Related Experiments (6)

Autophagy Enhancement Drug Screening for Neurodegeneration
clinical · proposed · Score: 0.40
Macroautophagy Dysfunction in PD - Experiment Design
clinical · proposed · Score: 0.40
Mutant Huntingtin (mHTT) Clearance Mechanisms — Therapeutic
validation · proposed · Score: 0.40
Pre-Symptomatic Tau Detection in MAPT Mutation Carriers
clinical · proposed · Score: 0.40
Proteasome-Ubiquitin System Dysfunction Validation in Parkin
clinical · proposed · Score: 0.40