K287N
Category 3/4 — Most DruggableUnknownCytoplasmic · predictedSource cardInteractive 3D Structure
Bond changes · DynaMut2 interaction analysis
| Interaction type | Wild-type partner | Mutant partner | Status |
|---|---|---|---|
| Ionic bond | E298 | — | Lost |
| Hydrogen bond | P279 | — | Lost |
| Hydrogen bond | L282 | — | Lost |
| Hydrogen bond | P283 | P283 | Preserved |
| Hydrogen bond | L284 | L284 | Preserved |
| Hydrogen bond | Y291 | Y291 | Preserved |
| Hydrogen bond | E298 | — | Lost |
| Polar contact | P279 | — | Lost |
| Polar contact | P283 | P283 | Preserved |
| Polar contact | L284 | L284 | Preserved |
| Polar contact | V289 | — | Lost |
| Polar contact | Y291 | Y291 | Preserved |
| Polar contact | E298 | — | Lost |
| Carbonyl | Y291 | Y291 | 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
- pLDDT 53.44 below 70
The underlying AlphaFold model has pLDDT below 70 at this position, so the structure the stability calculation was run on is itself uncertain.
Do not rank this value against a variant from a different region on ΔΔG alone.
Clinical Evidence
Not observed in ~730k individuals — consistent with a rare allele (ACMG PM2_supporting).
No ClinVar classification is recorded for this variant. The computed predictions on this card (AlphaMissense, DynaMut2, pLDDT) are the only evidence present, and they are structural predictions, not clinical classifications.
- Phenotype scope is interpretation of submitted records. The computed values on this card (AlphaMissense, DynaMut2 ΔΔG, pLDDT) are measurements of the model, not of a patient.
- Presentation cannot be generalised from neighbouring variants: one nucleotide over can present very differently. Structural similarity supports a mechanistic hypothesis, never a phenotype claim.
Review status: no ClinVar review status recorded. ClinVar "conditions" is the union of all submissions; 0–1★ entries are submitted conditions, not documented phenotypes.
No population breakdown — the variant is absent from gnomAD v4, so no ancestry group has an observed frequency.
No homozygotes — the variant is absent from gnomAD v4 altogether.
Source: gnomAD r4, retrieved 2026-08-21. Values are allele frequencies. The carrier estimate is derived from the allele frequency (Hardy-Weinberg, ~2·AF) and is an approximation, not a published figure — where a published carrier frequency exists it outranks this column and is cited on the card.
Full Variant Card
WFS1 Wolframin — K287N Variant Card
Molecular Atlas Pilot · RareResearch.AI · Generated by wolfram-variant-card skill
Lysine (K) → Asparagine (N) at position 287
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) |
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)
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 | Job 178092103937 · retrieved 2026-06-08 — result self-hosted by RareResearch.AI (Biosig no longer serves this page) |
Clinical Evidence
Inheritance and scope
No ClinVar classification
No ClinVar classification is recorded for this variant. The computed predictions on this card (AlphaMissense, DynaMut2, pLDDT) are the only evidence present, and they are structural predictions, not clinical classifications.
Phenotype scope is interpretation of submitted records. The computed values on this card (AlphaMissense, DynaMut2 ΔΔG, pLDDT) are measurements of the model, not of a patient. Presentation cannot be generalised from neighbouring variants: one nucleotide over can present very differently. Structural similarity supports a mechanistic hypothesis, never a phenotype claim.
| 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)
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.
Files in this folder
AF-O76024-F1-model_v6.pdb— AlphaFold structureK287N_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 cardK287N_dynamut2_summary.html— clean offline DynaMut2 result carddynamut2_result.json— structured result datadynamut2_result_page.html— local snapshot of the Biosig result page (asset URLs absolutized)K287N_wildtype_interactions.pse/K287N_mutant_interactions.pse— PyMOL sessions
Generated by wolfram-variant-card skill · RareResearch.AI Molecular Atlas Every assumption documented. Every score sourced.
Feed this card to Wolfram Intelligence
Download the K287N 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.