D171N
Category 4 — Stable Fold, Function DisruptedConflictingCytoplasmic · predictedEditorialAspartate → Asparagine at position 171 in N-terminal cytoplasmic domain. ClinVar Conflicting. AlphaMissense 0.20 (below threshold) — AM under-call. DynaMut2 ΔΔG -0.08 (neutral).
Interactive 3D Structure
Bond changes · DynaMut2 interaction analysis
| Interaction type | Wild-type partner | Mutant partner | Status |
|---|---|---|---|
| Ionic bond | R174 | — | Lost |
| Hydrogen bond | R174 | R174 | Preserved |
| Hydrogen bond | A175 | A175 | Preserved |
| Polar contact | R174 | R174 | Preserved |
| Polar contact | A175 | A175 | Preserved |
| Van der Waals | — | A175 | 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 at very low frequency in gnomAD.
Structural Context
Position 171 in cytoplasmic domain. Neighbors: THR170 (2.5 Å), LEU172 (2.5 Å), ARG174 (3.8 Å — R174 partner of R177C cluster region). The R174-D171 likely salt bridge.
D171N eliminates negative charge while preserving amide H-bond. R174 loses salt-bridge partner. ΔΔG ≈ 0; AM 0.20 under-call. ClinVar Conflicting with low evidence.
Druggability Assessment
Mechanism: loss of D171-R174 salt bridge. Therapeutic: same R174/R177 cluster microregion.
Why this matters
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Download the D171N 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.