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ATP7A

ATPase copper transporting alpha

The ATP7A gene encodes a protein vital for regulating copper levels in the body, playing a key role in its absorption and distribution to various enzymes. The ATP7A gene provides instructions for producing an ATPase copper-transporting alpha polypeptide.

Chromosome Xq21.1 X-linked HGNC:869 Tier C
ATP7A Xq21.1 p arm q arm X

ATP7A is located on the long (q) arm of chromosome X, at band Xq21.1. Arm ratio per GRCh38 - banding schematic.

Explore chromosome X in the library →

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Clinical tests that include this

Carrier Screening panel
ATP7A is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions
Newborn Genetic Screening panel
ATP7A is 1 of 258 genes on this panel
Genomic newborn screening for actionable paediatric conditions

Overview

The ATP7A gene, also known as ATPase copper transporting alpha, is critical for regulating copper homeostasis within the human body. Copper is an essential trace element required for various cellular processes, but it can be toxic in excessive amounts. The protein produced from the ATP7A gene is primarily responsible for transporting copper, ensuring its correct distribution and removal when necessary. Abnormalities in ATP7A function are linked to several inherited conditions.

What the gene does

The ATP7A protein functions as a copper-transporting ATPase, meaning it uses energy from ATP to move copper ions across cellular membranes. While largely absent from liver cells, this protein is found throughout the body, where it plays a dual role in copper management. In the small intestine, it facilitates the absorption of copper from dietary sources. Within other cells, the ATP7A protein typically resides in the Golgi apparatus, where it supplies copper to specific enzymes crucial for the development and function of bone, skin, hair, blood vessels, and the nervous system. When intracellular copper levels become elevated, the ATP7A protein relocates to the cell membrane to facilitate the efflux of excess copper from the cell, thus preventing toxicity.

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Chromosome location

The ATP7A gene is situated on the long arm of the X chromosome at band Xq21.1. This genomic location is significant because it leads to an X-linked inheritance pattern for conditions associated with this gene.

Protein structure

The ATP7A protein consists of 1500 amino acids. Its structure includes seven HMA domains: HMA 1 (amino acids 8-74), HMA 2 (amino acids 85-151), HMA 3 (amino acids 171-237), HMA 4 (amino acids 277-343), HMA 5 (amino acids 377-443), HMA 6 (amino acids 488-554), and HMA 7 (amino acids 564-630). Additionally, it features two Endocytosis signals (amino acids 1467-1468 and 1487-1488) and a PDZD11-binding region (amino acids 1486-1500), which are important for its trafficking and interaction within the cell.

Domain map · 1,500 amino acids
HMA 1 (8-74)HMA 2 (85-151)HMA 3 (171-237)HMA 4 (277-343)HMA 5 (377-443)HMA 6 (488-554)HMA 7 (564-630)Endocytosis signal (1467-1468)HMA 18-74HMA 285-151HMA 3171-2371~7501,500
Domain - independent functional unit
Motif - short conserved sequence
🧬 Explore 3D structure on AlphaFold
UniProt:Q04656Length:1,500 aaStructure:AlphaFold

Key variants

Variants within the ATP7A gene can lead to a range of inherited conditions by affecting the protein's ability to transport and regulate copper. These genetic changes can include deletions of gene segments, insertions of extra DNA building blocks, or single nucleotide alterations. Such variants can result in a non-functional or shortened ATP7A protein, leading to impaired copper metabolism.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for ATP7A.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1273del
Deletion
 p.Leu424_Leu425insTer Pathogenic ★★☆☆ Menkes kinky-hair syndrome
c.169C>T
single nucleotide variant
 p.Gln57Ter Pathogenic ★★☆☆ Cutis laxa, X-linked
c.2557G>T
single nucleotide variant
 p.Gly853Ter Pathogenic/Likely pathogenic ★★☆☆ Cutis laxa, X-linked
c.2922C>A
single nucleotide variant
 p.Tyr974Ter Pathogenic/Likely pathogenic ★★☆☆ Menkes kinky-hair syndrome
c.3111G>T
single nucleotide variant
 p.Lys1037Asn Pathogenic ★★☆☆ Menkes kinky-hair syndrome
c.31dup
Duplication
 p.Thr11fs Pathogenic/Likely pathogenic ★★☆☆ Inborn genetic diseases
c.3529C>T
single nucleotide variant
 p.Gln1177Ter Pathogenic ★★☆☆ Menkes kinky-hair syndrome
c.3799C>T
single nucleotide variant
 p.Gln1267Ter Pathogenic ★★☆☆ Inborn genetic diseases
c.3943G>A
single nucleotide variant
 p.Gly1315Arg Pathogenic/Likely pathogenic ★★☆☆ Menkes kinky-hair syndrome
c.4005+1G>T
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Menkes kinky-hair syndrome

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the ATP7A gene are associated with several inherited conditions, primarily impacting copper transport and resulting in diverse clinical presentations. These include Menkes disease, a severe neurodegenerative disorder, and its milder forms such as occipital horn syndrome, sometimes referred to as Menkes disease (occipital horn variant) or X-linked cutis laxa. Research has also examined potential links to other neurological conditions, such as Charcot-Marie-Tooth disease, where MedlinePlus Genetics provides further information.

Inheritance pattern

Conditions caused by pathogenic ATP7A variants typically follow X-linked inheritance.

Carrier frequency by population How common is heterozygous ATP7A carrier status across ancestry groups?

UK clinical status

The ATP7A gene is recognised within the UK's NHS Genomic Medicine Service, being listed on several PanelApp panels. These include green status on panels for DDG2P, Early onset or syndromic epilepsy, Ehlers Danlos syndrome with a likely monogenic cause (R101), Foetal anomalies (R21), Hereditary neuropathy, Hereditary neuropathy or pain disorder (R78), Intellectual disability, Likely inborn error of metabolism (R98), Skeletal dysplasia (R104), and Undiagnosed metabolic disorders, indicating its clinical relevance for diagnostics in these areas.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Ehlers Danlos syndrome with a likely monogenic cause · R101 NHS GMS → Fetal anomalies · R21 NHS GMS → Hereditary neuropathy or pain disorder · R78 NHS GMS → Likely inborn error of metabolism · R98 NHS GMS → Skeletal dysplasia · R104 NHS GMS → DDG2P NHS GMS → Early onset or syndromic epilepsy NHS GMS → Intellectual disability NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the primary function of the ATP7A gene?

The ATP7A gene provides instructions for a protein that is crucial for regulating copper levels in the body, ensuring its proper distribution to copper-dependent enzymes and facilitating the removal of excess copper from cells.

What conditions are associated with variants in the ATP7A gene?

Variants in the ATP7A gene are primarily associated with Menkes disease and its milder form, occipital horn syndrome. These conditions result from impaired copper transport and metabolism.

How does ATP7A relate to copper absorption?

In the small intestine, the ATP7A protein plays a key role in controlling the absorption of copper from food. Within other cells, it also helps supply copper to important enzymes and moves excess copper out of the cell.

References

  1. Bertini I, Rosato A. Menkes disease. Cellular and molecular life sciences : CMLS. 2008. PMID: 17989919
  2. Prohaska JR. Role of copper transporters in copper homeostasis. The American journal of clinical nutrition. 2008. PMID: 18779302
  3. Donsante A, Tang J, Godwin SC. Differences in ATP7A gene expression underlie intrafamilial variability in Menkes disease/occipital horn syndrome. Journal of medical genetics. 2007. PMID: 17496194
  4. de Bie P, Muller P, Wijmenga C. Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes. Journal of medical genetics. 2007. PMID: 17717039
  5. Tang J, Robertson S, Lem KE. Functional copper transport explains neurologic sparing in occipital horn syndrome. Genetics in medicine : official journal of the American College of Medical Genetics. 2006. PMID: 17108763
  6. Barnes N, Tsivkovskii R, Tsivkovskaia N. The copper-transporting ATPases, menkes and wilson disease proteins, have distinct roles in adult and developing cerebellum. The Journal of biological chemistry. 2005. PMID: 15634671
  7. Greenough M, Pase L, Voskoboinik I. Signals regulating trafficking of Menkes (MNK; ATP7A) copper-translocating P-type ATPase in polarized MDCK cells. American journal of physiology. Cell physiology. 2004. PMID: 15269005
  8. Harris ED. Basic and clinical aspects of copper. Critical reviews in clinical laboratory sciences. 2003. PMID: 14653357
  9. Voskoboinik I, Camakaris J. Menkes copper-translocating P-type ATPase (ATP7A): biochemical and cell biology properties, and role in Menkes disease. Journal of bioenergetics and biomembranes. 2002. PMID: 12539963
  10. Møller LB, Tümer Z, Lund C. Similar splice-site mutations of the ATP7A gene lead to different phenotypes: classical Menkes disease or occipital horn syndrome. American journal of human genetics. 2000. PMID: 10739752
  11. Kaler SG. Metabolic and molecular bases of Menkes disease and occipital horn syndrome. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 1998. PMID: 10463276
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 18 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .