ATOX1

Chr 5

antioxidant 1 copper chaperone

Also known as: ATX1, HAH1

NCBI Gene: 475ENSG00000177556UniProt: O00244

This gene encodes a copper chaperone that plays a role in copper homeostasis by binding and transporting cytosolic copper to ATPase proteins in the trans-Golgi network for later incorporation to the ceruloplasmin. This protein also functions as an antioxidant against superoxide and hydrogen peroxide, and therefore, may play a significant role in cancer carcinogenesis. Because of its cytogenetic location, this gene represents a candidate gene for 5q-syndrome. [provided by RefSeq, Jul 2008]

22
ClinVar variants
11
Pathogenic / LP
0.59
pLI score
0
Active trials
Clinical Summary— ATOX1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.59) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 10 VUS of 22 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
1.06LOEUF
pLI 0.586
Z-score 1.53
OE 0.00 (0.00–1.06)
Moderately constrained

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.
-0.06Z-score
OE missense 1.03 (0.79–1.35)
37 obs / 36.0 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.0.00 (0.00–1.06)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.79–1.35)
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.0.90
0≤1.21.6
LoF obs/exp: 0 / 2.7Missense obs/exp: 37 / 36.0Syn Z: 0.29

ClinVar Variant Classifications

22 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
VUS10
Likely Benign1
11
Pathogenic
10
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
0
0
0
VUS
0
8
2
0
10
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total0814022

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ATOX1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Copper metabolism in cell death and autophagy.
Xue Q et al.·Autophagy
2023Review
Balancing between cuproplasia and copper-dependent cell death: molecular basis and clinical implications of ATOX1 in cancer.
Suwara J et al.·J Exp Clin Cancer Res
2025Review
Exploring and clinical validation of prognostic significance and therapeutic implications of copper homeostasis-related gene dysregulation in acute myeloid leukemia.
Abulimiti M et al.·Ann Hematol
2024
Wilson's disease: an update.
Das SK et al.·Nat Clin Pract Neurol
2006Review
Transcriptional regulation of ATOX1 by PRRX2 impacts the progression and cuproptosis of hepatocellular carcinoma.
Tang L et al.·Cell Signal
2025
Genetic and environmental modifiers of Wilson disease.
Medici V et al.·Handb Clin Neurol
2017Review
Missing heritability of Wilson disease: a search for the uncharacterized mutations.
Roy S et al.·Mamm Genome
2023Review
Roles of Copper-Binding Proteins in Breast Cancer.
Blockhuys S et al.·Int J Mol Sci
2017Review
Copper enhances genotoxic drug resistance via ATOX1 activated DNA damage repair.
Jin J et al.·Cancer Lett
2022
Interaction between Copper Chaperone Atox1 and Parkinson's Disease Protein α-Synuclein Includes Metal-Binding Sites and Occurs in Living Cells.
Horvath I et al.·ACS Chem Neurosci
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
CRISPR-Cas9 screening identifies ATOX1-driven cisplatin resistance mechanisms in liver cancer and evaluates targeted inhibitor efficacy.
Hu C et al.·Commun Biol
2026Functional
The Copper Chaperone ATOX1 Exhibits Differential Protein-Protein Interactions and Contributes to Skeletal Myoblast Differentiation.
Ferguson N et al.·Mol Cell Biol
2026
m6A modification of ATOX1 inhibits acute myeloid leukemia progression by promoting cuproptosis.
Peng J et al.·Cancer Res Commun
2026
The effect of cuproptosis-related gene Atox1 on cardiac hypertrophy in heart failure was investigated based on bioinformatics analysis.
Zhou H et al.·Sci Rep
2025🔓 Open Access
ATOX1-driven ECM degradation and vascular smooth muscle cell apoptosis accelerate aortic dissection progression.
Xie Y et al.·Biochim Biophys Acta Mol Basis Dis
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools