FCER1G activation to create TREM2-bypass immune signaling through alternative receptor pathways
Curated pathway from expert analysis
flowchart TD
A["TREM2 Loss-of-Function<br/>R47H Variant or Shedding"]
B["Microglial Phagocytic Deficit<br/>Amyloid Debris Accumulation"]
C["FCER1G FcRgamma Expression<br/>Alternative Innate Immune Receptor"]
D["FCER1G Activation<br/>IgG-Opsonized Substrate Binding"]
E["ITAM Signaling via FcRgamma<br/>SYK LYN Kinase Activation"]
F["Bypass of TREM2-TYROBP<br/>Alternative DAP10/DAP12 Axis"]
G["Phagocytosis Restored<br/>TREM2-Independent Clearance"]
H["Amyloid Plaque Burden Reduced<br/>Microglial Function Preserved"]
A --> B
B -.->|"impaired clearance"| H
C --> D
D --> E
E --> F
F --> G
G --> H
style F fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style H fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for ['FCER1G'] yet. Search RCSB →
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 ['FCER1G'].
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF TREM2 is pharmacologically inhibited (anti-TREM2 blocking antibody) AND FCER1G is simultaneously overexpressed via plasmid transfection in microglia-like cells, THEN phagocytic activity and inflamm | TREM2 blockade alone will reduce phagocytosis by ~40-60% and alter cytokine profiles, but co-overexpression of FCER1G will rescue these functional deficits, res | — no observation — | pending | 0.68 |
| IF FCER1G is genetically silenced (siRNA) in human macrophage cell lines, THEN phospho-SYK and phospho-SLP-65 signaling pathway activation will decrease by >50% compared to control cells within 48 hou | FCER1G knockdown will significantly reduce downstream ITAM pathway activation markers (phospho-SYK, phospho-BLAT, phospho-ERK1/2) while baseline NF-κB activity | — no observation — | pending | 0.72 |