E385K
Category 3/4 — Most DruggableConflictingTransmembrane · predictedEditorialGlutamate → Lysine at position 385 in a connecting loop. ClinVar Conflicting including WFS1-Related Spectrum Disorders, monogenic diabetes. AlphaMissense 0.851, ΔΔG -0.16.
Interactive 3D Structure
Bond changes · DynaMut2 interaction analysis
| Interaction type | Wild-type partner | Mutant partner | Status |
|---|---|---|---|
| Ionic bond | K178 | — | Lost |
| Hydrogen bond | K178 | — | Lost |
| Hydrogen bond | L381 | L381 | Preserved |
| Hydrogen bond | L382 | L382 | Preserved |
| Hydrogen bond | L388 | L388 | Preserved |
| Polar contact | K178 | — | Lost |
| Polar contact | L381 | L381 | Preserved |
| Polar contact | — | L382 | Gained |
| Polar contact | N387 | N387 | Preserved |
| Polar contact | L388 | L388 | Preserved |
| Carbonyl | L382 | L382 | Preserved |
| Van der Waals | K178 | — | Lost |
| Hydrophobic | A175 | A175 | Preserved |
| Hydrophobic | — | K178 | Gained |
| Hydrophobic | A179 | A179 | Preserved |
| Hydrophobic | — | N387 | 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 in the general population.
Structural Context
Position 385 sits in a connecting loop. Neighbors: PHE384 (2.5 Å), PRO386 (2.5 Å), LEU381 (3.8 Å), LEU382 (4.2 Å — partner of L382P!). Adjacent to L382P region.
E385K charge-flips at this position. The variant lysine likely engages different partners than the wild-type glutamate. Combined with L382P, multiple Atlas variants converge on the 381-386 loop. ΔΔG mild; AM 0.851 + multi-phenotype confirm severe consequence.
Druggability Assessment
Mechanism: charge-flip in the L382-E385 loop. Therapeutic: same loop region as L382P.
Why this matters
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