A326T
Category 4 — Stable Fold, Function DisruptedConflictingTransmembrane · predictedEditorialAlanine → Threonine at position 326 inside TM1. ClinVar Conflicting including Wolfram + inborn diseases. AlphaMissense 0.13 (below threshold) — AM under-call. DynaMut2 ΔΔG -0.79. Third substitution at position 326 (with A326E, A326V).
Interactive 3D Structure
Bond changes · DynaMut2 interaction analysis
| Interaction type | Wild-type partner | Mutant partner | Status |
|---|---|---|---|
| Hydrogen bond | H322 | H322 | Preserved |
| Hydrogen bond | H323 | H323 | Preserved |
| Hydrogen bond | F329 | F329 | Preserved |
| Hydrogen bond | F330 | F330 | Preserved |
| Polar contact | H322 | H322 | Preserved |
| Polar contact | H323 | H323 | Preserved |
| Polar contact | I324 | I324 | Preserved |
| Polar contact | F329 | F329 | Preserved |
| Polar contact | F330 | F330 | Preserved |
| Van der Waals | — | H322 | Gained |
| Van der Waals | I324 | I324 | Preserved |
| Hydrophobic | F330 | F330 | 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 at very low frequency in gnomAD.
Structural Context
Position 326 same neighbors as A326E/A326V: ASN325 (2.5 Å), LEU327 (2.5 Å), HIS322 (3.6 Å).
A326T is the THIRD substitution at position 326 (with A326E charge, A326V volume). Position 326 is structurally inflexible regardless of substitution chemistry — three variants confirm this. AM 0.13 under-call; multi-phenotype confirms.
Druggability Assessment
Mechanism: polarity introduction at structurally critical TM1 position. Therapeutic: same TM1 microregion as A326E, A326V.
Why this matters
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Download the A326T 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.