K811R

Category 4 — Stable Fold, Function DisruptedConflictingLumenal · predictedσ-1 candidateEditorial

Lysine → Arginine at position 811 · C-terminal lumenal domain (653-869) · WFS1 (Wolframin)

Lys→Arg p811 lumenal AM=0.07 ddg=-0.28 pLDDT=86. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.

Interactive 3D Structure

Wild-type reference

Wild-type K811 — hydrogen bond to S808

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DynaMut2 mutant · K811R

Mutant R811 — polar contact to L814 lost (3 contacts lost)

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Bond changes · DynaMut2 interaction analysis

3 lost0 gained11 preserved

Interaction type	Wild-type partner	Mutant partner	Status
Hydrogen bond	S808	S808	Preserved
Hydrogen bond	L815	L815	Preserved
Polar contact	S808	S808	Preserved
Polar contact	E809	E809	Preserved
Polar contact	V813	V813	Preserved
Polar contact	L814	—	Lost
Polar contact	L815	L815	Preserved
Van der Waals	S808	S808	Preserved
Van der Waals	E809	E809	Preserved
Van der Waals	V813	—	Lost
Van der Waals	L815	L815	Preserved
Hydrophobic	Y773	—	Lost
Hydrophobic	F775	F775	Preserved
Hydrophobic	L815	L815	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

DynaMut2 ΔΔG

-0.28kcal/mol

Destabilising — mild

AlphaMissense

0.073

LBen

AlphaFold pLDDT

model confidence

Schema

Cat 4

Category 4 — Stable Fold, Function Disrupted

Clinical Evidence

ClinVar classificationConflicting classifications of pathogenicity

Review statuscriteria provided, conflicting classifications

Associated conditions(no specific conditions catalogued)

InheritanceConflicting ClinVar classifications.

Population frequency (gnomAD v4)Ultra-rare · AF 0.0029%

cDNA changec.2432A>G

ClinVar accessionVCV001160733

Last evaluated2025/05/21 00:00

Observed at very low frequency in gnomAD.

Structural Context

Position analysis: SER812 (2.5 Å), PHE810 (2.5 Å — F810L partner!), SER808 (3.8 Å — E809K region). Same E809-F810-K811 cluster as E809K/F810L. The Atlas's neighbor extraction surfaces this variant's contacts and connects them to the broader multi-variant target landscape.

Amino-acid chemistry

conservative basic-to-basic

Position in the protein

C-terminal lumenal domain

Druggability Assessment

Cat 4 — see structural prose. AlphaMissense below threshold (AM under-call class) but mechanism is structurally identified. Therapeutic strategy: site-directed at contacts identified above, or wet-lab validation if pLDDT borderline/below 50.

Why this matters

E809K + F810L + K811R cluster.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the K811R 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.

Download K811R PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin

Topological domain653–869 · Lumenal