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Genetics Home Reference: your guide to understanding genetic conditions
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ATP7A

Reviewed June 2009

What is the official name of the ATP7A gene?

The official name of this gene is “ATPase, Cu++ transporting, alpha polypeptide.”

ATP7A is the gene's official symbol. The ATP7A gene is also known by other names, listed below.

What is the normal function of the ATP7A gene?

The ATP7A gene provides instructions for making a protein that is important for regulating copper levels in the body. Copper is necessary for many cellular functions, but it is toxic when present in excessive amounts. The ATP7A protein is found throughout the body, except in liver cells. In the small intestine, this protein helps control the absorption of copper from food. In other cells, the ATP7A protein has a dual role and shuttles between two cellular locations. The protein normally resides in a cell structure called the Golgi apparatus, which modifies newly produced proteins, including enzymes. In the Golgi apparatus, the ATP7A protein supplies copper to certain enzymes that are critical for the structure and function of bone, skin, hair, blood vessels, and the nervous system. If copper levels in the cell environment are elevated, however, the ATP7A protein moves to the cell membrane and eliminates excess copper from the cell.

Does the ATP7A gene share characteristics with other genes?

The ATP7A gene belongs to a family of genes called ATP (ATPases).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the ATP7A gene related to health conditions?

cutis laxa - caused by mutations in the ATP7A gene

Several mutations in the ATP7A gene are responsible for a condition called occipital horn syndrome or X-linked cutis laxa, which is considered a mild form of Menkes syndrome. Occipital horn syndrome is characterized by loose and sagging skin, wedge-shaped calcium deposits in a bone at the base of the skull (the occipital bone), coarse hair, and loose joints.

Most of the mutations that cause occipital horn syndrome reduce but do not eliminate the production of the ATP7A protein. A shortage of this protein impairs the absorption of copper from food and prevents its normal distribution to cells throughout the body. The decreased supply of copper can reduce the activity of numerous copper-containing enzymes, affecting the structure and function of bone, skin, hair, blood vessels, and the nervous system. The reduced activity of these enzymes underlies the characteristic features of occipital horn syndrome.

Menkes syndrome - caused by mutations in the ATP7A gene

Researchers have identified more than 150 mutations in the ATP7A gene that cause Menkes syndrome. Many of these mutations delete part of the gene and likely result in a shortened ATP7A protein. Other mutations insert additional DNA building blocks (nucleotides) into the gene or change single nucleotides. All of these mutations prevent the production of functional ATP7A protein. As a result, the absorption of copper from food is impaired, and copper is not supplied to certain enzymes. The abnormal protein may get stuck in the cell membrane and become unable to shuttle back and forth from the Golgi apparatus.

The disrupted activity of the ATP7A protein causes copper to be poorly distributed to cells in the body. Copper accumulates in some tissues, such as the small intestine and kidneys, while the brain and other tissues have unusually low levels. The decreased supply of copper can reduce the activity of numerous copper-containing enzymes, affecting the structure and function of bone, skin, hair, blood vessels, and the nervous system. The signs and symptoms of Menkes syndrome are caused by the reduced activity of these copper-containing enzymes.

Where is the ATP7A gene located?

Cytogenetic Location: Xq21.1

Molecular Location on the X chromosome: base pairs 77,910,655 to 78,050,394

The ATP7A gene is located on the long (q) arm of the X chromosome at position 21.1.

The ATP7A gene is located on the long (q) arm of the X chromosome at position 21.1.

More precisely, the ATP7A gene is located from base pair 77,910,655 to base pair 78,050,394 on the X chromosome.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about ATP7A?

You and your healthcare professional may find the following resources about ATP7A helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the ATP7A gene or gene products?

  • ATP7A_HUMAN
  • ATPase, Cu++ transporting, alpha polypeptide (Menkes syndrome)
  • ATPP1
  • copper pump 1
  • MC1
  • MK
  • MNK
  • OHS

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding ATP7A?

calcium ; cell ; cell membrane ; DNA ; gene ; Golgi apparatus ; intestine ; nervous system ; protein ; syndrome ; toxic

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • OMIM: ATPase, Cu(2+)-TRANSPORTING, ALPHA POLYPEPTIDE (http://omim.org/entry/300011)
  • Barnes N, Tsivkovskii R, Tsivkovskaia N, Lutsenko S. The copper-transporting ATPases, menkes and wilson disease proteins, have distinct roles in adult and developing cerebellum. J Biol Chem. 2005 Mar 11;280(10):9640-5. Epub 2005 Jan 5. (http://www.ncbi.nlm.nih.gov/pubmed/15634671?dopt=Abstract)
  • Bertini I, Rosato A. Menkes disease. Cell Mol Life Sci. 2008 Jan;65(1):89-91. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17989919?dopt=Abstract)
  • de Bie P, Muller P, Wijmenga C, Klomp LW. Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes. J Med Genet. 2007 Nov;44(11):673-88. Epub 2007 Aug 23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17717039?dopt=Abstract)
  • Donsante A, Tang J, Godwin SC, Holmes CS, Goldstein DS, Bassuk A, Kaler SG. Differences in ATP7A gene expression underlie intrafamilial variability in Menkes disease/occipital horn syndrome. J Med Genet. 2007 Aug;44(8):492-7. Epub 2007 May 11. Erratum in: J Med Genet. 2008 Jan;45(1):64. (http://www.ncbi.nlm.nih.gov/pubmed/17496194?dopt=Abstract)
  • Greenough M, Pase L, Voskoboinik I, Petris MJ, O'Brien AW, Camakaris J. Signals regulating trafficking of Menkes (MNK; ATP7A) copper-translocating P-type ATPase in polarized MDCK cells. Am J Physiol Cell Physiol. 2004 Nov;287(5):C1463-71. Epub 2004 Jul 21. (http://www.ncbi.nlm.nih.gov/pubmed/15269005?dopt=Abstract)
  • Harris ED. Basic and clinical aspects of copper. Crit Rev Clin Lab Sci. 2003 Oct;40(5):547-86. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14653357?dopt=Abstract)
  • Kaler SG. Metabolic and molecular bases of Menkes disease and occipital horn syndrome. Pediatr Dev Pathol. 1998 Jan-Feb;1(1):85-98. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10463276?dopt=Abstract)
  • Møller LB, Tümer Z, Lund C, Petersen C, Cole T, Hanusch R, Seidel J, Jensen LR, Horn N. Similar splice-site mutations of the ATP7A gene lead to different phenotypes: classical Menkes disease or occipital horn syndrome. Am J Hum Genet. 2000 Apr;66(4):1211-20. Epub 2000 Mar 17. (http://www.ncbi.nlm.nih.gov/pubmed/10739752?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/538)
  • Prohaska JR. Role of copper transporters in copper homeostasis. Am J Clin Nutr. 2008 Sep;88(3):826S-9S. (http://www.ncbi.nlm.nih.gov/pubmed/18779302?dopt=Abstract)
  • Tang J, Robertson S, Lem KE, Godwin SC, Kaler SG. Functional copper transport explains neurologic sparing in occipital horn syndrome. Genet Med. 2006 Nov;8(11):711-8. (http://www.ncbi.nlm.nih.gov/pubmed/17108763?dopt=Abstract)
  • Voskoboinik I, Camakaris J. Menkes copper-translocating P-type ATPase (ATP7A): biochemical and cell biology properties, and role in Menkes disease. J Bioenerg Biomembr. 2002 Oct;34(5):363-71. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12539963?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: June 2009
Published: September 15, 2014