🧪
hypothesis

Sphingosine-1-Phosphate Gradient Disruption

Hypothesis

Sphingosine-1-Phosphate Gradient Disruption

Convergent myelopathy phenotype results from disruption of S1P gradient that maintains immune cell trafficking and barrier function in spinal cord, with different etiologies converging by altering S1P metabolism.
🧬 S1PR1🩺 neuroinflammation🎯 Composite 46%💱 $0.52▲5.2%active
EvidencePending (0%)📖 5 cit🗣 1 debates 5 support 2 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 0.35 (8%) 0.455 composite
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arXiv PreprintNeurIPSNature MethodsPLOS ONE
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Composite46%

🧪 Overview

Convergent myelopathy phenotype results from disruption of S1P gradient that maintains immune cell trafficking and barrier function in spinal cord, with different etiologies converging by altering S1P metabolism.

🧬 Mechanism

🔗 Mechanism from KG for S1PR1

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

graph TD
    Fingolimod["Fingolimod"] -->|associated with| S1PR1["S1PR1"]
    siponimod["siponimod"] -->|associated with| S1PR1_1["S1PR1"]
    S1PR1_2["S1PR1"] -->|controls| immune_cell_trafficking["immune cell trafficking"]
    S1PR1_3["S1PR1"] -->|maintains| blood_spinal_cord_barrier["blood-spinal cord barrier"]
    S1PR1_4["S1PR1"] -->|associated with| immune_cell_trafficking_5["immune cell trafficking"]
    S1PR1_6["S1PR1"] -->|associated with| blood_brain_barrier["blood_brain_barrier"]
    style Fingolimod fill:#4fc3f7,stroke:#333,color:#000
    style S1PR1 fill:#4fc3f7,stroke:#333,color:#000
    style siponimod fill:#4fc3f7,stroke:#333,color:#000
    style S1PR1_1 fill:#4fc3f7,stroke:#333,color:#000
    style S1PR1_2 fill:#ce93d8,stroke:#333,color:#000
    style immune_cell_trafficking fill:#4fc3f7,stroke:#333,color:#000
    style S1PR1_3 fill:#ce93d8,stroke:#333,color:#000
    style blood_spinal_cord_barrier fill:#4fc3f7,stroke:#333,color:#000
    style S1PR1_4 fill:#4fc3f7,stroke:#333,color:#000
    style immune_cell_trafficking_5 fill:#4fc3f7,stroke:#333,color:#000
    style S1PR1_6 fill:#4fc3f7,stroke:#333,color:#000
    style blood_brain_barrier fill:#4fc3f7,stroke:#333,color:#000

⚖️ Evidence

⚖️ Evidence Matrix5 supports0 contradicts
Supports
Significance of sphingosine-1-phosphate in cardiovascular physiology and pathology.
Pharmacol Res2020PMID:32278039medium
Supports
Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis.
Drugs2021PMID:33983615medium
Supports
ApoM-bound S1P acts via endothelial S1PR1 to suppress choroidal neovascularization and vascular leakage.
Angiogenesis2025PMID:40266369medium
Supports
Targeting the Sphingosine-1-Phosphate Pathway: New Opportunities in Inflammatory Bowel Disease Management.
Drugs2024PMID:39322927medium
Supports
Dysfunctional S1P/S1PR1 signaling in the dentate gyrus drives vulnerability of chronic pain-related memory impairment.
Elife2024PMID:39699949medium
📖 Linked Papers

No linked papers recorded for this hypothesis yet.

🏥 Translation

🧬 3D Protein Structure — S1PR1

No curated PDB or AlphaFold mapping for S1PR1 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 S1PR1 →

No DepMap CRISPR Chronos data found for S1PR1.

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
0.0511
Events (7d)
0
Price History
▲5.2%

💾 Resource Usage

LLM Tokens
12,040
$0.0722
Total Cost
$0.0722
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