Bivalent Domain Resolution Failure at Neurodevelopment Genes
Curated pathway from expert analysis
flowchart TD
A["Bivalent Domain Resolution<br/>Hypothesis Target"]
B["Pathway Dysregulation<br/>Cited Mechanism"]
C["Cellular Response<br/>Stress or Clearance Change"]
D["Neural Circuit Effect<br/>Synapse/Glia Vulnerability"]
E["Neurodegeneration<br/>Disease-Relevant Outcome"]
A --> B
B --> C
C --> D
D --> E
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style B fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style E fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for BIVALENT yet. Search RCSB →
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 Bivalent Domain Resolution.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF bivalent domain resolution failure contributes to neurodegeneration, THEN siRNA-mediated knockdown of the H3K27me3 demethylase KDM6B in iPSC-derived cortical neurons will dysregulate neurodevelopme | ≥50% of neurodevelopment genes (n≥200 with bivalent domains in undifferentiated NPCs) will show ≥2-fold expression change after KDM6B knockdown at day 30 of dif | — no observation — | pending | 0.35 |
| IF bivalent domain resolution fails at neurodevelopment genes in neurodegeneration, THEN ChIP-seq will show significantly higher co-occupancy of H3K4me3 and H3K27me3 at these loci in prefrontal cortex | ≥30% increase in bivalent domain peaks at neurodevelopment genes (GO:0007422, GO:0048666) in AD prefrontal cortex (Brodmann area 9) relative to controls, detect | — no observation — | pending | 0.45 |