A342T
Category 4 — Stable Fold, Function DisruptedConflictingTransmembrane · predictedEditorialAlanine → Threonine at position 342 inside TM2. ClinVar Conflicting including WFS1 spectrum + Wolfram. AlphaMissense 0.13 (below threshold) — AM under-call. DynaMut2 ΔΔG -0.72.
Interactive 3D Structure
Bond changes · DynaMut2 interaction analysis
| Interaction type | Wild-type partner | Mutant partner | Status |
|---|---|---|---|
| Hydrogen bond | I338 | I338 | Preserved |
| Hydrogen bond | D339 | D339 | Preserved |
| Hydrogen bond | — | W867 | Gained |
| Polar contact | I338 | I338 | Preserved |
| Polar contact | D339 | D339 | Preserved |
| Polar contact | — | F340 | Gained |
| Polar contact | P346 | P346 | Preserved |
| Polar contact | — | W867 | Gained |
| Van der Waals | — | D339 | Gained |
| Van der Waals | — | F340 | Gained |
| Van der Waals | P346 | — | Lost |
| Van der Waals | — | W867 | Gained |
| Hydrophobic | W867 | W867 | Preserved |
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 342 at TM2 start. Neighbors: PHE343 (2.4 Å), PHE341 (2.5 Å — aromatic cluster start), TRP867 (3.6 Å — long-range to TM11 W867!). The W867 contact is structurally significant — TM2-TM11 cross-helix contact.
A342T introduces polarity into TM2 + perturbs TM2-TM11 cross-helix W867 contact. AM 0.13 under-call; multi-phenotype confirms.
Druggability Assessment
Mechanism: polarity in TM2 + TM2-TM11 W867 cross-helix disruption. Therapeutic: TM2-TM11 interface.
Why this matters
Feed this card to Wolfram Intelligence
Download the A342T 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.