ATP7A

Chr X

ATPase copper transporting alpha

Also known as: DSMAX, HMNX, MK, MNK, SMAX3

NCBI Gene: 538ENSG00000165240UniProt: Q04656

This gene encodes a transmembrane protein that functions in copper transport across membranes. This protein is localized to the trans Golgi network, where it is predicted to supply copper to copper-dependent enzymes in the secretory pathway. It relocalizes to the plasma membrane under conditions of elevated extracellular copper, and functions in the efflux of copper from cells. Mutations in this gene are associated with Menkes disease, X-linked distal spinal muscular atrophy, and occipital horn syndrome. Alternatively-spliced transcript variants have been observed. [provided by RefSeq, Aug 2013]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMenkes disease
UniProtOccipital horn syndrome
UniProtNeuronopathy, distal hereditary motor, X-linked

Clinical highlights

Gene-disease validity (ClinGen)
Menkes disease · XLDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
146
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.22
LOEUF· LoF intol.
LOF
Mechanism· G2P
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GeneReview available — ATP7A
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.22LOEUF
pLI 1.000
Z-score 5.47
OE 0.09 (0.04–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.53Z-score
OE missense 0.82 (0.76–0.88)
448 obs / 548.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.09 (0.04–0.22)
0≤0.351.4
Missense OE?0.82 (0.76–0.88)
0≤0.61.4
Synonymous OE?0.82
0≤1.21.6
LoF obs/exp: 4 / 42.4Missense obs/exp: 448 / 548.9Syn Z: 2.00

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ATP7A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients