D797V
Category 3/4 — Most DruggableConflictingLumenal · predictedσ-1 candidateEditorialAspartate → Valine at position 797 in lumenal domain. ClinVar Conflicting. AlphaMissense 0.876, ΔΔG +0.04 (neutral). pLDDT 65 borderline.
Interactive 3D Structure
Bond changes · DynaMut2 interaction analysis
| Interaction type | Wild-type partner | Mutant partner | Status |
|---|---|---|---|
| Hydrogen bond | E794 | E794 | Preserved |
| Hydrogen bond | T799 | — | Lost |
| Hydrogen bond | K800 | K800 | Preserved |
| Polar contact | E794 | E794 | Preserved |
| Polar contact | T799 | T799 | Preserved |
| Polar contact | K800 | K800 | Preserved |
| Van der Waals | — | T799 | Gained |
| Hydrophobic | — | T799 | Gained |
| Hydrophobic | K800 | — | 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
Not observed in ~730k individuals — consistent with a rare allele (ACMG PM2_supporting).
Structural Context
Position 797 sits in the lumenal C-terminal region. Neighbors: VAL798 (2.4 Å), ASP796 (2.4 Å — adjacent aspartate), GLU794 (4.2 Å), THR799 (4.3 Å).
Replacing D797 with valine eliminates the negative charge in a local charged cluster (D796, E794 nearby). Fold accommodates (ΔΔG essentially zero). AlphaMissense 0.876 confirms severe consequence. Same position as D797N — both pathogenic.
Druggability Assessment
Mechanism: charge loss from local D796-D797-E794 cluster. Therapeutic: site-directed at this charge cluster.
Why this matters
Feed this card to Wolfram Intelligence
Download the D797V 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.