TDP-43 Phase Separation Destabilization Drives Cytoplasmic Aggregation
🧪 Overview
Aberrant arginine methylation prevents TDP-43 liquid-liquid phase separation, promoting pathogenic aggregation. PRMT5-mediated asymmetric dimethylation of RGG motifs in TDP-43 normally maintains phase separation competence. Under stress, hypomethylation or excessive methylation both disrupt LLPS, causing TDP-43 to transition from liquid droplets directly to solid aggregates.
🧬 Mechanism
⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — TDP-43
No curated PDB or AlphaFold mapping for TDP-43 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.
No DepMap CRISPR Chronos data found for TDP-43 (TARDBP), PRMT5.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
📊 Market Indicators
💾 Resource Usage
No resource usage or linked notebooks recorded for this hypothesis yet.
▸Metadataorigin_type: debate_synthesizer
| origin_type | debate_synthesizer |
| target_gene | TDP-43 (TARDBP), PRMT5 |
| _schema_version | 1 |
| composite_score | 0.5 |