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.
Health Conditions Related to Genetic Changes
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 (described below). 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.More About This Health Condition
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.More About This Health Condition
MedlinePlus Genetics provides information about Charcot-Marie-Tooth diseaseMore About This Health Condition
Other Names for This Gene
- ATPase, Cu++ transporting, alpha polypeptide
- ATPase, Cu++ transporting, alpha polypeptide (Menkes syndrome)
- copper pump 1
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
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- Bertini I, Rosato A. Menkes disease. Cell Mol Life Sci. 2008 Jan;65(1):89-91. doi: 10.1007/s00018-007-7439-6. Citation on PubMed
- 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. doi: 10.1136/jmg.2007.052746. Epub 2007 Aug 23. Citation on PubMed or Free article on PubMed Central
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- Harris ED. Basic and clinical aspects of copper. Crit Rev Clin Lab Sci. 2003 Oct;40(5):547-86. Citation on PubMed
- Kaler SG. Metabolic and molecular bases of Menkes disease and occipital horn syndrome. Pediatr Dev Pathol. 1998 Jan-Feb;1(1):85-98. doi: 10.1007/s100249900011. Citation on PubMed
- Moller LB, Tumer 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. doi: 10.1086/302857. Epub 2000 Mar 17. Citation on PubMed or Free article on PubMed Central
- Prohaska JR. Role of copper transporters in copper homeostasis. Am J Clin Nutr. 2008 Sep;88(3):826S-9S. doi: 10.1093/ajcn/88.3.826S. Citation on PubMed or Free article on PubMed Central
- 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. doi: 10.1097/01.gim.0000245578.94312.1e. Citation on PubMed
- 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. doi: 10.1023/a:1021250003104. Citation on PubMed
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