🧪
hypothesis

Nuclear Import Receptor Enhancers as Phase Separation Modulators

Hypothesis

Nuclear Import Receptor Enhancers as Phase Separation Modulators

Small molecules that enhance nuclear import receptor binding affinity could prevent pathological TDP-43 phase transitions by maintaining proper nuclear-cytoplasmic partitioning.
🧬 TARDBP🎯 Composite 0%💱 $0.51▲1.3%proposed
neurodegeneration
EvidenceModerate (50%)📖 0 cit🗣 1 debates 1 support 0 oppose
✓ All Quality Gates Passed
Mechanistic 0.60 (15%) Evidence 0.55 (15%) Novelty 0.60 (12%) Feasibility 0.00 (12%) Impact 0.00 (12%) Druggability 0.00 (10%) Safety 0.00 (8%) Competition 0.00 (6%) Data Avail. 0.00 (5%) Reproducible 0.00 (5%) KG Connect 0.50 (8%) 0.000 composite
☰ Compare⚔️ Duel⚛️ Collide
📄 Export LaTeX
arXiv PreprintNeurIPSNature MethodsPLOS ONE
📖 Export BibTeXinteract with this hypothesis
Composite0%

🧪 Overview

Small molecules that enhance nuclear import receptor binding affinity could prevent pathological TDP-43 phase transitions by maintaining proper nuclear-cytoplasmic partitioning.

Debate provenance: derived from debate `sess_SDA-2026-04-11-sda-2026-04-01-gap-006` on question: TDP-43 phase separation therapeutics for ALS-FTD. Consensus signal: domain_expert, skeptic, synthesizer, theorist discussed the mechanism terms Enhancers, Import, Modulators, Nuclear, Phase, Receptor, Separation, TARDBP. Novelty signal: skeptic-discussed-with-qualified-concession.

🧬 Mechanism

🔗 Mechanism from KG for TARDBP

Auto-built from this analysis's top knowledge-graph edges.

graph TD
    TARDBP["TARDBP"] -->|associated with| neurodegeneration["neurodegeneration"]
    TARDBP_1["TARDBP"] -->|participates in| TDP_43_RNA_processing___p["TDP-43 RNA processing / phase separation"]
    TGM2["TGM2"] -->|co discussed| TARDBP_2["TARDBP"]
    TARDBP_3["TARDBP"] -->|co discussed| PRMT1["PRMT1"]
    TARDBP_4["TARDBP"] -->|co discussed| PARP1["PARP1"]
    TARDBP_5["TARDBP"] -->|co discussed| HSPA1A["HSPA1A"]
    TARDBP_6["TARDBP"] -->|co discussed| G3BP1["G3BP1"]
    TARDBP_7["TARDBP"] -->|co discussed| SRPK1["SRPK1"]
    PRMT1_8["PRMT1"] -->|co discussed| TARDBP_9["TARDBP"]
    HSPA1A_10["HSPA1A"] -->|co discussed| TARDBP_11["TARDBP"]
    G3BP1_12["G3BP1"] -->|co discussed| TARDBP_13["TARDBP"]
    SRPK1_14["SRPK1"] -->|co discussed| TARDBP_15["TARDBP"]
    PARP1_16["PARP1"] -->|co discussed| TARDBP_17["TARDBP"]
    HSPA1A_18["HSPA1A"] -->|co associated with| TARDBP_19["TARDBP"]
    PRMT1_20["PRMT1"] -->|co associated with| TARDBP_21["TARDBP"]
    style TARDBP fill:#ce93d8,stroke:#333,color:#000
    style neurodegeneration fill:#ef5350,stroke:#333,color:#000
    style TARDBP_1 fill:#ce93d8,stroke:#333,color:#000
    style TDP_43_RNA_processing___p fill:#81c784,stroke:#333,color:#000
    style TGM2 fill:#ce93d8,stroke:#333,color:#000
    style TARDBP_2 fill:#ce93d8,stroke:#333,color:#000
    style TARDBP_3 fill:#ce93d8,stroke:#333,color:#000
    style PRMT1 fill:#ce93d8,stroke:#333,color:#000
    style TARDBP_4 fill:#ce93d8,stroke:#333,color:#000
    style PARP1 fill:#ce93d8,stroke:#333,color:#000
    style TARDBP_5 fill:#ce93d8,stroke:#333,color:#000
    style HSPA1A fill:#ce93d8,stroke:#333,color:#000
    style TARDBP_6 fill:#ce93d8,stroke:#333,color:#000
    style G3BP1 fill:#ce93d8,stroke:#333,color:#000
    style TARDBP_7 fill:#ce93d8,stroke:#333,color:#000
    style SRPK1 fill:#ce93d8,stroke:#333,color:#000
    style PRMT1_8 fill:#ce93d8,stroke:#333,color:#000
    style TARDBP_9 fill:#ce93d8,stroke:#333,color:#000
    style HSPA1A_10 fill:#ce93d8,stroke:#333,color:#000
    style TARDBP_11 fill:#ce93d8,stroke:#333,color:#000
    style G3BP1_12 fill:#ce93d8,stroke:#333,color:#000
    style TARDBP_13 fill:#ce93d8,stroke:#333,color:#000
    style SRPK1_14 fill:#ce93d8,stroke:#333,color:#000
    style TARDBP_15 fill:#ce93d8,stroke:#333,color:#000
    style PARP1_16 fill:#ce93d8,stroke:#333,color:#000
    style TARDBP_17 fill:#ce93d8,stroke:#333,color:#000
    style HSPA1A_18 fill:#ce93d8,stroke:#333,color:#000
    style TARDBP_19 fill:#ce93d8,stroke:#333,color:#000
    style PRMT1_20 fill:#ce93d8,stroke:#333,color:#000
    style TARDBP_21 fill:#ce93d8,stroke:#333,color:#000

⚖️ Evidence

📖 Linked Papers

No linked papers recorded for this hypothesis yet.

🏥 Translation

🧬 3D Protein Structure — TARDBP

🧬 PDB 4BS2 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

💉 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 TARDBP →

No DepMap CRISPR Chronos data found for TARDBP.

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
▲ 0.0%
Volatility
Low
0.0002
Events (7d)
1
Price History
▲1.3%

💾 Resource Usage

LLM Tokens
51,518
$0.3091
Total Cost
$0.3091
View on SciDEX ↗