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ATP7A

ATPase copper transporting alpha

The ATP7A gene provides instructions for producing a protein vital for regulating copper levels within the body, ensuring proper cellular function and preventing toxicity. The ATP7A gene encodes a copper-transporting ATPase, a protein essential for maintaining appropriate copper balance in cells.

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, plays a critical role in managing copper metabolism throughout the human body. Copper is an essential trace element required for numerous biological processes, including enzyme function and connective tissue development, but it must be tightly regulated to avoid cellular damage.

The protein produced from the ATP7A gene helps absorb copper from food in the small intestine and distributes it to copper-dependent enzymes within cells. It also facilitates the removal of excess copper when levels become too high, acting as a cellular gatekeeper for this vital metal.

What the gene does

The ATP7A gene provides instructions for a copper-transporting P-type ATPase, a protein primarily responsible for copper homeostasis. This protein is widely distributed across the body's tissues, excluding liver cells. Within the small intestine, the ATP7A protein is involved in the absorption of dietary copper.

Inside other cells, the ATP7A protein has a dynamic function. It typically resides in the Golgi apparatus, where it supplies copper to enzymes that require it for their structure and activity. These copper-dependent enzymes are essential for the healthy development and function of tissues such as bone, skin, hair, blood vessels, and the nervous system. If intracellular copper levels rise, the ATP7A protein can relocate to the cell membrane to actively transport and eliminate the surplus copper from the cell, thus preventing copper toxicity.

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Chromosome location

The ATP7A gene is situated on the long arm of the X chromosome at position 21.1, a location denoted as Xq21.1. As an X-linked gene, its inheritance pattern differs between males and females.

Protein structure

The ATP7A protein consists of 1500 amino acids. It features several key functional regions. There are seven heavy metal-associated (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, the protein contains two distinct Endocytosis signal motifs located at amino acids 1467-1468 and 1487-1488, which are important for its internalisation. A PDZD11-binding region is also present at amino acids 1486-1500.

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 clinical presentations, primarily affecting copper metabolism. Over 150 different types of genetic changes have been identified, including deletions, insertions, and single nucleotide substitutions. These variants can disrupt the production of a functional ATP7A protein, impairing its ability to regulate copper levels effectively.

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.3111G>T
single nucleotide variant
 p.Lys1037Asn Pathogenic ★★☆☆ Menkes kinky-hair syndrome
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
c.4085C>T
single nucleotide variant
 p.Ala1362Val Pathogenic/Likely pathogenic ★★☆☆ Menkes kinky-hair syndrome
c.412C>T
single nucleotide variant
 p.Gln138Ter Pathogenic/Likely pathogenic ★★☆☆ ATP7A-related disorder
c.422_423del
Microsatellite
 p.Glu141fs Pathogenic/Likely pathogenic ★★☆☆ Menkes kinky-hair syndrome
c.466_467insC
Insertion
 p.Lys156fs Pathogenic ★★☆☆ Menkes kinky-hair syndrome
c.1707del
Deletion
 p.Val569_Val570insTer Pathogenic ★☆☆☆ not provided
c.2872_2882del
Deletion
 p.Val958fs Pathogenic ★☆☆☆ not provided

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, predominantly affecting copper transport and metabolism. The most severe of these is Menkes disease (XLR), a neurodegenerative disorder characterised by severe copper deficiency in many tissues. A milder presentation, often considered a variant of Menkes disease, is Occipital horn syndrome (XLR), sometimes referred to as Menkes disease (occipital horn variant) (XLR), which involves connective tissue abnormalities and distinctive bone features.

Inheritance pattern

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

♀ Carrier mother 1 altered X ♂ Unaffected father Typical Y Carrier daughter Unaffected daughter Affected son Unaffected son Affected Carrier Unaffected Circles = females · Squares = males

X-linked recessive: sons of a carrier mother have a 50% chance of being affected. Daughters have a 50% chance of being carriers.

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

UK clinical status

The ATP7A gene is recognised in several UK NHS national genomic testing panels, indicating its clinical significance within the NHS Genomic Medicine Service. It is included in panels such as DDG2P, Early onset or syndromic epilepsy, and Hereditary neuropathy. Furthermore, ATP7A is part of the panels for Ehlers Danlos syndrome with a likely monogenic cause (R101), Foetal anomalies (R21), Hereditary neuropathy or pain disorder (R78), Intellectual disability, Likely inborn error of metabolism (R98), Skeletal dysplasia (R104), and Undiagnosed metabolic disorders, all showing a 'green' status for evidence.

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 role of the ATP7A gene?

The ATP7A gene is crucial for regulating copper levels in the body. It produces a protein that helps absorb dietary copper, distributes it to necessary enzymes, and removes excess copper from cells to prevent toxicity.

Which conditions are associated with variants in the ATP7A gene?

Variants in the ATP7A gene are primarily associated with conditions affecting copper metabolism, such as Menkes disease and Occipital horn syndrome. These conditions lead to various health issues due to impaired copper transport.

How does ATP7A manage copper within cells?

The ATP7A protein typically resides in the Golgi apparatus, where it supplies copper to enzymes. If copper levels become too high, it moves to the cell membrane to export the excess copper, maintaining cellular balance.

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 20 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .