DPP6-linked neuronal regulatory networks controlling synaptic excitability and cognitive resilience in PD should produce a measurable proximal phenotype before late disease pathology. The decisive test is cell-type eQTL colocalization, enhancer perturbation, and prodromal PD single-nucleus validation in hippocampal and prefrontal neurons.
Curated pathway from expert analysis
flowchart TD
A["DPP6 GWAS Hit<br/>Potassium Channel Modulator"]
B["K+ Channel Surfacing at<br/>Active Zone Dendritic Shaft"]
C["AP Action Potential Repolarization<br/>Shorter Duration, Faster K+ Clearance"]
D["Dendritic Excitability Dampened<br/>Reduced Ca2+ Influx Through VGCC"]
E["Synaptic Plasticity Shift<br/>LTP vs LTD Balance Favoring Stability"]
F["Cognitive Resilience in PD<br/>Executive Function Preservation"]
G["DPP6 Risk Allele carriers<br/>Faster Cognitive Decline Trajectory"]
A --> B
B --> C
C --> D
D --> E
E --> F
A --> G
G --> F
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for DPP6 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 DPP6.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.