V871M
Category 4 — Stable Fold, Function DisruptedConflictingLumenal · predictedσ-1 candidateEditorialValine → Methionine at position 871 inside TM11. ClinVar Conflicting including WFS1 spectrum + monogenic diabetes. AlphaMissense 0.14 (below threshold) — AM under-call. DynaMut2 ΔΔG -0.15. Same position as V871G.
Interactive 3D Structure
Bond changes · DynaMut2 interaction analysis
| Interaction type | Wild-type partner | Mutant partner | Status |
|---|---|---|---|
| Hydrogen bond | W867 | W867 | Preserved |
| Hydrogen bond | — | R868 | Gained |
| Hydrogen bond | A874 | A874 | Preserved |
| Hydrogen bond | V875 | V875 | Preserved |
| Polar contact | W867 | W867 | Preserved |
| Polar contact | — | R868 | Gained |
| Polar contact | G873 | — | Lost |
| Polar contact | A874 | A874 | Preserved |
| Polar contact | V875 | V875 | Preserved |
| Van der Waals | — | I421 | Gained |
| Van der Waals | W867 | — | Lost |
| Van der Waals | G873 | — | Lost |
| Van der Waals | A874 | — | Lost |
| Hydrophobic | — | I421 | Gained |
| Hydrophobic | V875 | — | Lost |
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 871 same neighbors as V871G: HIS872 (2.5 Å), THR870 (2.5 Å), TRP867 (3.7 Å).
V871M conservative chemistry at the V871 position. AM 0.14 under-call; multi-phenotype confirms.
Druggability Assessment
Mechanism: methionine chemistry shift at TM11 start. Therapeutic: same TM11 cluster.
Why this matters
Feed this card to Wolfram Intelligence
Download the V871M 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.