D866N
Category 4 — Stable Fold, Function DisruptedConflictingLumenal · predictedσ-1 candidateEditorialAspartate → Asparagine at position 866. ClinVar Conflicting including monogenic diabetes + Wolfram. AlphaMissense 0.18 (below threshold) — AM under-call. DynaMut2 ΔΔG -0.59.
Interactive 3D Structure
Bond changes · DynaMut2 interaction analysis
| Interaction type | Wild-type partner | Mutant partner | Status |
|---|---|---|---|
| Ionic bond | K862 | — | Lost |
| Hydrogen bond | K862 | — | Lost |
| Hydrogen bond | E864 | — | Lost |
| Hydrogen bond | S869 | S869 | Preserved |
| Hydrogen bond | T870 | T870 | Preserved |
| Polar contact | K862 | K862 | Preserved |
| Polar contact | E864 | E864 | Preserved |
| Polar contact | R868 | — | Lost |
| Polar contact | S869 | S869 | Preserved |
| Polar contact | T870 | T870 | Preserved |
| Van der Waals | R868 | R868 | Preserved |
| Van der Waals | — | T870 | Gained |
Lost / gained / preserved interatomic contacts at the variant residue, from the DynaMut2 (Arpeggio) interaction analysis of the wild-type and energy-minimized mutant structures.
Computational Predictions
Clinical Evidence
Observed in the general population.
Structural Context
Position 866 in C-terminal cluster. Neighbors: TRP867 (2.5 Å), HIS865 (2.5 Å — partner of E864K via H865), ARG868 (4.3 Å — R868H!). The 864-868 cluster has E864K, H865 (E864K's neighbor), D866N (this card), R868H — four variants/positions in five residues.
D866N charge loss in dense multi-variant cluster. AM 0.18 under-call; multi-phenotype confirms.
Druggability Assessment
Mechanism: charge loss in dense 864-868 cluster. Therapeutic: same C-terminal cluster.
Why this matters
Feed this card to Wolfram Intelligence
Download the D866N PDF below and upload it to Wolfram Intelligence to generate therapeutic-strategy proposals — guanidinium mimetics, sigma-1 agonist docking, NAC thiol-capping. NAC is already on the bench-testing list.