Nuclear Pore Complex Integrity as Proteostasis Checkpoint Failure
🧪 Overview
Age-dependent Nup358 degradation enables pathogenic protein import into the nucleus. Decreased Nup358 expression with aging leads to defective nuclear pore complex gating. This allows abnormal accumulation of disease proteins within the nucleoplasm where they can interact with splicing machinery and transcriptional regulators.
🧬 Mechanism
⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — RANBP2
No curated PDB or AlphaFold mapping for RANBP2 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 RANBP2.
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 | RANBP2/Nup358, importin-β |
| _schema_version | 1 |
| composite_score | 0.46 |