ATP7B

Chr 13AR

ATPase copper transporting beta

Also known as: PWD, WC1, WD, WND

NCBI Gene: 540 ENSG00000123191 UniProt: P35670

This gene is a member of the P-type cation transport ATPase family and encodes a protein with several membrane-spanning domains, an ATPase consensus sequence, a hinge domain, a phosphorylation site, and at least 2 putative copper-binding sites. This protein is a monomer, and functions as a copper-transporting ATPase which exports copper out of the cells, such as the efflux of hepatic copper into the bile. Alternate transcriptional splice variants, encoding different isoforms with distinct cellular localizations, have been characterized. Mutations in this gene have been associated with Wilson disease which is characterized by copper accumulation. [provided by RefSeq, Dec 2019]

Primary Disease Associations & Inheritance

Wilson diseaseMIM #277900

282

ClinVar variants

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— ATP7B

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Gene-Disease Validity (ClinGen)

Wilson disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

49 Pathogenic / Likely Pathogenic· 154 VUS of 282 total submissions

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Clinical Trials

10 active or recruiting trials — potential therapeutic options may be available

Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

1.19LOEUF

pLI 0.000

Z-score 0.45

OE 0.93 (0.74–1.19)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

-0.88Z-score

OE missense 1.09 (1.03–1.15)

885 obs / 814.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.93 (0.74–1.19)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.09 (1.03–1.15)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07

0≤1.21.6

LoF obs/exp: 47 / 50.4Missense obs/exp: 885 / 814.3Syn Z: -1.02

ClinVar Variant Classifications

282 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25

Likely Pathogenic24

VUS154

Likely Benign77

Benign2

Pathogenic

Likely Pathogenic

154

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	18	0	7	0	25
Likely Pathogenic	14	6	4	0	24
VUS	3	125	22	4	154
Likely Benign	0	4	30	43	77
Benign	1	0	1	0	2
Total	36	135	64	47	282

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

ATPase, Cu(2+)-TRANSPORTING, BETA POLYPEPTIDE; ATP7B

MIM #606882 · *

Wilson disease

MIM #277900

Molecular basis of disorder known

Autosomal recessive

External Resources

Links to major genomics databases and tools

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GeneReview available — ATP7B

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Literature

Landmark / reviewRecent case evidence

Key Publications

Landmark & review papers · by relevance

PubMed

Wilson disease.

Członkowska A et al.·Nat Rev Dis Primers

2018Review

Wilson's disease: overview.

Lucena-Valera A et al.·Med Clin (Barc)

2023Review

Clinical and genetic characterization of a large cohort of patients with Wilson's disease in China.

Zhang S et al.·Transl Neurodegener

2022Cohort

A genetic study of Wilson's disease in the United Kingdom.

Coffey AJ et al.·Brain

2013

Wilson's disease: update on pathogenesis, biomarkers and treatments.

Shribman S et al.·J Neurol Neurosurg Psychiatry

2021Review

Wilson's disease and other neurological copper disorders.

Bandmann O et al.·Lancet Neurol

2015Review

Wilson Disease: An Overview and Approach to Management.

Mulligan C et al.·Neurol Clin

2020Review

Spectrum and Classification of ATP7B Variants in a Large Cohort of Chinese Patients with Wilson's Disease Guides Genetic Diagnosis.

Dong Y et al.·Theranostics

2016Cohort

Wilson disease in children and young adults - State of the art.

Chanpong A et al.·Saudi J Gastroenterol

2022Review

Diverse functional properties of Wilson disease ATP7B variants.

Huster D et al.·Gastroenterology

2012Functional

Top 10 resultsSearch PubMed ↗

Recent Gene-Specific Literature

Gene in title · MEDLINE · newest first

Europe PMC

Relative Exchangeable Copper Confirms Wilson Disease and Supports Reclassification of the ATP7B p.Met665Ile Variant With Conflicting Pathogenicity Evidence.

Nicastro E et al.·Am J Med Genet A

2026

Analyses of ATP7B mRNA in Nasopharyngeal Swab Samples Increase Yields of Wilson Disease Molecular Genetic Diagnostics.

Steiner Mrázová L et al.·Hum Mutat

2026🔓 Open Access

ATP7B-maintained copper stores in myeloid progenitors are required for functional maturation of neutrophils.

Dev S et al.·Cell Rep

2026Functional

The mechanism of CISD3 regulating NRF2-ATP7B to ameliorate alcohol-induced liver mitochondrial dysfunction and cuproptosis.

Huang J et al.·Int Immunopharmacol

2026Functional

Novel and less invasive biomarker assays to measure liver ATP7B in Wilson disease patients.

Jiang RJ et al.·Sci Rep

2025🔓 Open AccessCohort

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Wilson DiseaseD-PenicillamineEffect of D-penicilline on Cutaneous Elastity of Wilson's Patient

Wilson's Disease Treated With D-Penicillamine: Characterization of Skin Damage Secondary to Treatment by Measuring Skin Elasticity

RECRUITING

NCT06945081Phase NACentre Hospitalier Universitaire de Saint EtienneStarted 2025-11-28

Preparation of forearm molds with SILFLO® silicone

Wilson Disease

Prescreening Study to Identify Potential Wilson Disease Participants for Gene-Editing Clinical Trial

RECRUITING

NCT07226622Prime Medicine, Inc.Started 2025-12-29

Wilson's Disease

Multifaceted 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 RECRUITING

NCT07241832Assiut UniversityStarted 2025-12-01

KAB-pB Scores

Wilson Disease

Gene Therapy for Wilson Disease Evaluated by 64Cu PET/CT

ENROLLING BY INVITATION

NCT07159581Thomas Damgaard SandahlStarted 2025-07-08

Wilson Disease

Phase I/II Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of GC310 Injection in Patients With Wilson's Disease (WD)

NOT YET RECRUITING

NCT07173933Phase PHASE1, PHASE2GeneCradle IncStarted 2025-10

GC310