# WFS1 Wolframin — K287N Variant Card

**Molecular Atlas Pilot · RareResearch.AI · Generated by wolfram-variant-card skill**

*Lysine (K) → Asparagine (N) at position 287*

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## Identity

| Field | Value |
|---|---|
| **Variant** | K287N (p.Lysine287Asparagine) |
| **DNA change** | c.861G>T |
| **Gene · Protein** | WFS1 · Wolframin (890 aa) |
| **UniProt** | O76024 · WFS1_HUMAN |
| **ClinVar accession** | VCV004306964 |
| **Amino acid change** | Lysine (K) → Asparagine (N) |

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## Structural Context

| Field | Value |
|---|---|
| **AlphaFold model** | AF-O76024-F1, v6 |
| **pLDDT at residue 287** | **53.44** — confident |
| **Domain** | N-terminal cytoplasmic (intrinsically disordered) |
| **Position context** | N-terminal cytoplasmic (intrinsically disordered) |
| **IDR flag** | No — pLDDT above 50 threshold |

**UniProt features at this position:**

  (none catalogued)



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## Computational Predictions

### AlphaMissense
| Field | Value |
|---|---|
| am_pathogenicity | **0.9311** |
| am_class | **likely pathogenic** |
| Interpretation | Likely pathogenic (threshold 0.564) |

### DynaMut2
| Field | Value |
|---|---|
| ΔΔG (kcal/mol) | **-0.78 (Destabilising)** |
| Job ID | 178092103937 |
| Result URL | https://biosig.lab.uq.edu.au/dynamut2/results_prediction/178092103937 |

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## Clinical Evidence

| Field | Value |
|---|---|
| Classification | **None** |
| Review status | None |
| Last evaluated | 1/01/01 00:00 |
| Inheritance | — |
| WFS1 variant landscape | K287N is 1 of ~326 pathogenic-spectrum variants in WFS1 (out of 2,243 catalogued in ClinVar) |

(no conditions catalogued)

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## Research Path Decision Tree

```
ΔΔG < 2  + binding site affected   →  CATEGORY 3 — docking experiments
ΔΔG 2–4                            →  CATEGORY 2 — pharmacological chaperones
ΔΔG > 4                            →  CATEGORY 1 — gene therapy
pLDDT < 50                         →  CATEGORY 5 — IDR, experimental only
Stable fold + functional site hit  →  CATEGORY 4 — site-specific docking
```

## Final Schema Categorization

**Category 3/4 — Most Druggable**

Mildly destabilizing fold; AlphaMissense confirms functional impact. Fold intact, specific local contacts/sites disrupted. Priority for docking and pharmacological chaperone screening.



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## Files in this folder

- `AF-O76024-F1-model_v6.pdb` — AlphaFold structure
- `K287N_molstar_viewer.html` — interactive 3D viewer (auto-highlights position 287 with ball-and-stick + neighbors within 5Å)
- `K287N_variant_card.md` — this card (source of truth)
- `K287N_variant_card.html` — styled printable card
- `K287N_dynamut2_summary.html` — clean offline DynaMut2 result card
- `dynamut2_result.json` — structured result data
- `dynamut2_result_page.html` — local snapshot of the Biosig result page (asset URLs absolutized)
- `K287N_wildtype_interactions.pse` / `K287N_mutant_interactions.pse` — PyMOL sessions

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*Generated by wolfram-variant-card skill · RareResearch.AI Molecular Atlas*
*Every assumption documented. Every score sourced.*