R42Q

Category 5 — IDR ExclusionConflictingCytoplasmic · predictedEditorial

Arginine → Glutamine at position 42 · N-terminal intrinsically disordered region (1-86) · WFS1 (Wolframin)

Arg→Gln p42 IDR AM=0.07 ddg=-0.05 pLDDT=29. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.

Interactive 3D Structure

Wild-type reference

Wild-type R42 — native residue, no strong sidechain contacts

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DynaMut2 mutant · R42Q

Mutant Q42 — energy-minimized; local contact network preserved

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Computational Predictions

DynaMut2 ΔΔG

-0.05kcal/mol

Destabilising — mild

AlphaMissense

0.069

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)Ultra-rare · AF 0.0011%

cDNA changec.125G>A

ClinVar accessionVCV000517412

Last evaluated2025/06/12 00:00

Observed at very low frequency in gnomAD.

Structural Context

Position analysis: ALA43 (2.4 Å — A43V!), PRO41 (2.5 Å), ARG40 (4.8 Å). pLDDT 29 deep IDR. Adjacent to A43V. 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

N-terminal IDR

Druggability Assessment

Cat 5 IDR — 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

IDR adjacent to A43V.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the R42Q 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 R42Q PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin

Region1–321 · Interaction with ATP6V1A

Region1–86 · Disordered