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ID: h-b3ff662404
Hypothesis

USP13 Stabilization of PINK1/Parkin Mitophagy in Parkinson's Disease

USP13 deubiquitinates and stabilizes PINK1 and Parkin, enhancing mitophagy.
🧬 USP13🩺 neurodegeneration🎯 Composite 39%💱 $0.46▲16.3%proposed
EvidencePending (0%)📖 0 cit🗣 1 debates✓ 2 support✗ 5 oppose
✓ All Quality Gates Passed
Mechanistic 0.48 (15%) Evidence 0.32 (15%) Novelty 0.85 (12%) Feasibility 0.15 (12%) Impact 0.35 (12%) Druggability 0.10 (10%) Safety 0.25 (8%) Competition 0.85 (6%) Data Avail. 0.28 (5%) Reproducible 0.30 (5%) KG Connect 0.50 (8%) 0.393 composite
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Composite39%

🧪 Overview

USP13 deubiquitinates and stabilizes PINK1 and Parkin, enhancing mitophagy. USP13 downregulation in sporadic PD brains leads to damaged mitochondrial accumulation. USP13 restoration may enhance mitophagy and protect dopaminergic neurons, though no tool compounds exist and mechanism validation is incomplete.

🧬 Mechanism

No curated mechanism pathway recorded for this hypothesis.

⚖️ Evidence

⚖️ Evidence Matrix2 supports5 contradicts
Supports
USP13 knockdown impairs Parkin-mediated mitophagy
Supports
USP13 protein decreased in PD substantia nigra
Contradicts
USP13 knockout mice develop mitochondrial dysfunction with age (unpublished/preprint only - inadmissible)
Contradicts
PINK1/Parkin mutations cause <5% of PD (early-onset, atypical) - limited relevance to sporadic disease
Contradicts
Parkin overexpression trials (AAV-Parkin) failed in PD models
Contradicts
No precedent for deubiquitinase activators (DUB inhibitors exist for cancer, not activators)
Contradicts
PINK1/Parkin knockout mice develop mitochondrial defects but no dopaminergic neurodegeneration
📖 Linked Papers

No linked papers recorded for this hypothesis yet.

🏥 Translation

🧬 3D Protein Structure — USP13

No curated PDB or AlphaFold mapping for USP13 yet. Search RCSB →

💉 Clinical Trials

No clinical trials data linked to this hypothesis yet.

No curated ClinVar variants loaded for this hypothesis.

Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.

🔍 Search ClinVar for USP13 →

No DepMap CRISPR Chronos data found for USP13.

Run python3 scripts/backfill_hypothesis_depmap.py to populate.

🏆 Tournament

🏆 Arenas / Elo

No arena matches recorded yet. Browse Arenas →

📊 Market Indicators

7d Trend
↔
Stable
7d Momentum
▲ 0.8%
Volatility
Low
0.0050
Events (7d)
3
Price History
▲16.3%

💾 Resource Usage

No resource usage or linked notebooks recorded for this hypothesis yet.

▸Metadataorigin_type: debate_synthesizer
origin_typedebate_synthesizer
target_geneUSP13
_schema_version1
composite_score0.393
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting 0 contradicting 0 neutral
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