Disease dossier · ORPHAN-015

Wilson Disease

ATP7B · Metabolic / Metal Overload

TJ Compassion + L.O.V.E. verified registry ORPHA 905 OMIM 277900

01At a glance

Gene
ATP7B
Protein
Copper-transporting ATPase 2UniProt P35670 · 1465 aa
Inheritance
Autosomal recessive — ATP7B mutations
Age of onset
Variable — hepatic (childhood/adolescence) or neuropsychiatric (adolescence/adulthood)
Prevalence
~1 in 30,000 — commonly cited; UNVERIFIED exact figure this sessionMarked unverified in the registry
Category
Metabolic / Metal Overload
Mechanism class
chelatable_metal
Clinical trials
84 studiesClinicalTrials.gov, 2 Nov 2026

02What it is

Wilson disease is an autosomal recessive disorder of copper transport caused by ATP7B deficiency, leading to toxic copper accumulation in the liver, brain, and cornea. It presents with liver disease, neuropsychiatric symptoms, and Kayser-Fleischer rings. Treatment is copper chelation and zinc — removing the toxic metal, a strategy distinct from degradation or replacement.

03What goes wrong

Loss-of-function copper transporter leading to copper overload. ATP7B normally exports copper into bile; its deficiency causes copper to accumulate in the liver, brain, and cornea. The pathology is driven by the toxic copper overload (a downstream metal accumulation), not by a toxic protein aggregate and not by a simple enzyme-replaceable deficiency.

04How NIGHTINGALE routes it

mechanism: chelatable_metal not a degradation target

Recommended modality: chelator (remove excess copper — penicillamine, trientine) + zinc (block absorption)

NOT eligible (protein-level). The disease is copper overload due to a loss-of-function transporter; the correct intervention is copper CHELATION (remove the toxic metal) or zinc therapy (block absorption), not protein degradation or enzyme replacement.

05Treatment today

D-Penicillamine and Trientine (chelators); Zinc acetate (absorption blocker)

Penicillamine/trientine/zinc long-established for Wilson disease
Copper chelator + zinc · penicillamine 149.2 Da · trientine 146.2 Da · zinc acetate 183.5 Da

Chelators bind and promote urinary excretion of excess copper; zinc induces metallothionein to block intestinal copper absorption. Both lower body copper burden.

06In the pipeline

Key reference: PMID 10441329 · PubMed

07Verification

Every line below is the registry's own verification record — what was checked, against which source, and what is still open.

08Sources

FactSourceAccessionRetrieved
Gene/protein identityUniProtP35670 (ATP7B, 1465 aa)2026-10-04
Disease classification & definitionOrphanetORPHAcode 905 (Wilson disease)2026-10-04
Inheritance & geneticsOMIM277900 (Wilson Disease)2026-10-04
Source record: ORPHAN-015.json — orphan registry v2.0-fresh-2026-10-04. Protocol: TJ Compassion + L.O.V.E. — every fact live-verified against UniProt / PubChem / ClinVar / OMIM / FDA / Orphanet
Fresh orphan registry entry built 2026-10-04 under the orphan-disease-verification skill. Mechanism: chelatable metal overload (copper).
Corrections carried into registry v2 (2)
  • VERIFIED (2026-10-04): built fresh. ORPHAcode 905 confirmed live via Orphanet API.
  • CLARIFIED: Wilson is a CHELATABLE METAL overload disease — the correct modality is copper CHELATION (remove the toxic metal), not protein degradation, not enzyme replacement, not a channel drug.

09Scope and limits

This page is a research summary for teaching and scientific communication. It is not medical advice, a diagnosis, or a treatment recommendation. NEXUS NIGHTINGALE is a computational research pipeline; it is not clinically validated and none of its output has regulatory approval. Prevalence and approval figures marked unverified must be confirmed against the cited source before external use.
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