ATP7B
Chr 13ARATPase copper transporting beta
Also known as: PWD, WC1, WD, WND
The protein functions as a copper-transporting ATPase that exports copper out of cells, particularly ensuring efflux of copper from hepatocytes into bile to maintain copper homeostasis in the liver. Mutations cause Wilson disease, an autosomal recessive disorder characterized by pathological copper accumulation in tissues. The disease mechanism involves loss of normal copper export function leading to toxic copper buildup primarily in the liver and brain.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
600 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 42 | 2 | 2 | 0 | 46 |
Likely Pathogenic | 44 | 22 | 0 | 0 | 66 |
VUS | 6 | 280 | 35 | 15 | 336 |
Likely Benign | 0 | 5 | 46 | 77 | 128 |
Benign | 1 | 0 | 1 | 0 | 2 |
Conflicting | — | 4 | |||
| Total | 93 | 309 | 84 | 92 | 582 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ATP7B · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Phase 1/2/3 Study of UX701 Gene Therapy in Adults With Wilson Disease
ACTIVE NOT RECRUITINGPrescreening Study to Identify Potential Wilson Disease Participants for Gene-Editing Clinical Trial
ACTIVE NOT RECRUITINGDescription of the Copper Concentration in Breast Milk in Women Treated for Wilson's Disease
RECRUITINGPhase I/II Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of GC310 Injection in Patients With Wilson's Disease (WD)
NOT YET RECRUITINGMultifaceted Assessment of Patients With Wilson's Disease in a Low-Resource Setting in Upper Egypt: Service Integration, Psychosocial Burden, Dietary Practices, and the Geo-Spatial Disease Map
NOT YET RECRUITINGA Phase I/II Study of VTX-801 in Adult Patients With Wilson's Disease
ACTIVE NOT RECRUITINGGene Therapy for Wilson Disease Evaluated by 64Cu PET/CT
ENROLLING BY INVITATIONWilson's Disease Treated With D-Penicillamine: Characterization of Skin Damage Secondary to Treatment by Measuring Skin Elasticity
RECRUITINGA Clinical Study to Evaluate the Safety and Efficacy of LY-M003 Injection in Patients With Wilson Disease
RECRUITINGAn Exploratory Study to Evaluate the Tolerability and Safety of MWAV201 in Subjects With Wilson Disease
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools