🧪
hypothesis

Phase Separation Modulation Therapy

Hypothesis

Phase Separation Modulation Therapy

Disruption of biomolecular condensates that facilitate seed propagation while preserving normal phase separation functions.
🧬 FUS🩺 neurodegeneration🎯 Composite 46%💱 $0.52▲6.0%active
EvidencePending (0%)📖 5 cit🗣 1 debates 5 support 1 oppose
✓ All Quality Gates Passed
Mechanistic 0.50 (15%) Evidence 0.50 (15%) Novelty 0.50 (12%) Feasibility 0.50 (12%) Impact 0.00 (12%) Druggability 0.50 (10%) Safety 0.50 (8%) Competition 0.50 (6%) Data Avail. 0.50 (5%) Reproducible 0.50 (5%) KG Connect 0.37 (8%) 0.455 composite
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arXiv PreprintNeurIPSNature MethodsPLOS ONE
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Composite46%

🧪 Overview

Disruption of biomolecular condensates that facilitate seed propagation while preserving normal phase separation functions

🧬 Mechanism

🔗 Mechanism from KG for FUS

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

graph TD
    ATP6V1A["ATP6V1A"] -->|encodes subunit of| v_ATPase["v-ATPase"]
    ATP6V1A_1["ATP6V1A"] -->|encodes subunit of| lysosomal_acidification["lysosomal acidification"]
    lysosomal_acidification_2["lysosomal acidification"] -->|associated with| PROTEIN_DEGRADATION["PROTEIN_DEGRADATION"]
    HSPA1A["HSPA1A"] -->|regulates| PROTEIN_FOLDING["PROTEIN_FOLDING"]
    PROTEIN_FOLDING_3["PROTEIN_FOLDING"] -.->|inhibits| PROTEIN_AGGREGATION["PROTEIN_AGGREGATION"]
    v_ATPase_4["v-ATPase"] -->|modulates| lysosomal_pH["lysosomal pH"]
    lysosomal_acidification_5["lysosomal acidification"] -->|enables| protein_degradation["protein degradation"]
    protein_degradation_6["protein degradation"] -->|protects against| neurodegeneration["neurodegeneration"]
    ATF5["ATF5"] -->|transcriptional ac| UPRmt["UPRmt"]
    UPRmt_7["UPRmt"] -->|regulates| mitochondrial_proteostasi["mitochondrial proteostasis"]
    mitochondrial_proteostasi_8["mitochondrial proteostasis"] -->|resists| seed_induced_protein_misf["seed-induced protein misfolding"]
    HSPA1A_9["HSPA1A"] -->|facilitates| protein_folding["protein folding"]
    style ATP6V1A fill:#ce93d8,stroke:#333,color:#000
    style v_ATPase fill:#4fc3f7,stroke:#333,color:#000
    style ATP6V1A_1 fill:#ce93d8,stroke:#333,color:#000
    style lysosomal_acidification fill:#81c784,stroke:#333,color:#000
    style lysosomal_acidification_2 fill:#81c784,stroke:#333,color:#000
    style PROTEIN_DEGRADATION fill:#81c784,stroke:#333,color:#000
    style HSPA1A fill:#ce93d8,stroke:#333,color:#000
    style PROTEIN_FOLDING fill:#4fc3f7,stroke:#333,color:#000
    style PROTEIN_FOLDING_3 fill:#4fc3f7,stroke:#333,color:#000
    style PROTEIN_AGGREGATION fill:#4fc3f7,stroke:#333,color:#000
    style v_ATPase_4 fill:#4fc3f7,stroke:#333,color:#000
    style lysosomal_pH fill:#4fc3f7,stroke:#333,color:#000
    style lysosomal_acidification_5 fill:#81c784,stroke:#333,color:#000
    style protein_degradation fill:#4fc3f7,stroke:#333,color:#000
    style protein_degradation_6 fill:#4fc3f7,stroke:#333,color:#000
    style neurodegeneration fill:#ef5350,stroke:#333,color:#000
    style ATF5 fill:#ce93d8,stroke:#333,color:#000
    style UPRmt fill:#81c784,stroke:#333,color:#000
    style UPRmt_7 fill:#81c784,stroke:#333,color:#000
    style mitochondrial_proteostasi fill:#4fc3f7,stroke:#333,color:#000
    style mitochondrial_proteostasi_8 fill:#4fc3f7,stroke:#333,color:#000
    style seed_induced_protein_misf fill:#4fc3f7,stroke:#333,color:#000
    style HSPA1A_9 fill:#ce93d8,stroke:#333,color:#000
    style protein_folding fill:#4fc3f7,stroke:#333,color:#000

⚖️ Evidence

⚖️ Evidence Matrix5 supports0 contradicts
Supports
FUS-dependent liquid-liquid phase separation is important for DNA repair initiation.
J Cell Biol2021PMID:33704371medium
Supports
Phase Separation of FUS Is Suppressed by Its Nuclear Import Receptor and Arginine Methylation.
Cell2018PMID:29677514medium
Supports
Antisense oligonucleotide silencing of FUS expression as a therapeutic approach in amyotrophic lateral sclerosis.
Nat Med2022PMID:35075293medium
Supports
FUS gene mutation in amyotrophic lateral sclerosis: a new case report and systematic review.
Amyotroph Lateral Scler Frontotemporal Degener2024PMID:37926865medium
Supports
Functional Ultrasound Neuroimaging.
Annu Rev Neurosci2022PMID:35803584medium
📖 Linked Papers

No linked papers recorded for this hypothesis yet.

🏥 Translation

🧬 3D Protein Structure — FUS

🧬 PDB 4FDD 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 FUS →

No DepMap CRISPR Chronos data found for FUS.

Run python3 scripts/backfill_hypothesis_depmap.py to populate.

🏆 Tournament

🏆 Arenas / Elo

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📊 Market Indicators

7d Trend
Stable
7d Momentum
▲ 0.0%
Volatility
High
0.0535
Events (7d)
0
Price History
▲6.0%

💾 Resource Usage

LLM Tokens
15,500
$0.0930
Total Cost
$0.0930
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