D267N

Category 5 — IDR ExclusionConflictingCytoplasmic · predictedEditorial

Aspartate → Asparagine at position 267 · N-terminal cytoplasmic domain (87-313) · WFS1 (Wolframin)

Asp→Asn p267 N-term AM=0.11 ddg=+0.77 pLDDT=31. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.

Interactive 3D Structure

Wild-type reference

Wild-type D267 — hydrogen bond to L265

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DynaMut2 mutant · D267N

Mutant N267 — van der waals contact to L265 lost

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Bond changes · DynaMut2 interaction analysis

1 lost0 gained2 preserved

Interaction type	Wild-type partner	Mutant partner	Status
Hydrogen bond	L265	L265	Preserved
Polar contact	L265	L265	Preserved
Van der Waals	L265	—	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

DynaMut2 ΔΔG

0.77kcal/mol

Stabilising — mild

AlphaMissense

0.109

LBen

AlphaFold pLDDT

model confidence

Schema

Cat 5

Category 5 — IDR Exclusion

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)Low frequency · AF 0.041%

cDNA changec.799G>A

ClinVar accessionVCV000166577

Last evaluated2026/01/21 00:00

Observed in the general population.

Structural Context

Position analysis: ASP268 (2.5 Å — adjacent existing D), GLN266 (2.5 Å), LEU265 (4.2 Å). pLDDT 31 deep IDR. DynaMut2 untrustworthy. The Atlas's neighbor extraction surfaces this variant's contacts.

Amino-acid chemistry

charge loss, H-bond preserved

Position in the protein

N-terminal cytoplasmic IDR-boundary

Druggability Assessment

Category 5 — see structural prose. AlphaMissense below threshold (AM under-call class) but mechanism is structurally clear from neighbor analysis. Therapeutic strategy: site-directed at the contacts identified above.

Why this matters

deep IDR — wet-lab required.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the D267N 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 D267N PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin

Region1–321 · Interaction with ATP6V1A