R587Q

Category 4 — Stable Fold, Function DisruptedConflictingTransmembrane · predictedEditorial

Arginine → Glutamine at position 587 · Connecting loop · WFS1 (Wolframin)

Arg→Gln p587 loop AM=0.08 ddg=-0.05 pLDDT=77. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.

Interactive 3D Structure

Wild-type reference

Wild-type R587 — hydrogen bond to L583

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DynaMut2 mutant · R587Q

Mutant Q587 — hydrogen bond contact to T590 lost

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Bond changes · DynaMut2 interaction analysis

0 lost0 gained8 preserved

Interaction type	Wild-type partner	Mutant partner	Status
Hydrogen bond	L583	L583	Preserved
Hydrogen bond	T590	T590	Preserved
Hydrogen bond	S591	S591	Preserved
Polar contact	L583	L583	Preserved
Polar contact	Q584	Q584	Preserved
Polar contact	T590	T590	Preserved
Polar contact	S591	S591	Preserved
Van der Waals	S591	S591	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

-0.05kcal/mol

Destabilising — mild

AlphaMissense

0.081

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)Low frequency · AF 0.028%

cDNA changec.1760G>A

ClinVar accessionVCV000215361

Last evaluated2025/12/30 00:00

Observed in the general population.

Structural Context

Position analysis: TRP588 (2.4 Å), ALA586 (2.5 Å — same loop as R587W), THR590 (3.5 Å). Same position as R587W. The Atlas's neighbor extraction surfaces this variant's contacts and connects them to the broader multi-variant target landscape.

Amino-acid chemistry

charge loss, amide preserved

Position in the protein

Connecting loop

Druggability Assessment

Cat 3/4 — 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

R587W + R587Q sister variants.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the R587Q 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 R587Q PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin