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Genetics Home Reference: your guide to understanding genetic conditions
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ABCC6

Reviewed January 2015

What is the official name of the ABCC6 gene?

The official name of this gene is “ATP-binding cassette, sub-family C (CFTR/MRP), member 6.”

ABCC6 is the gene's official symbol. The ABCC6 gene is also known by other names, listed below.

What is the normal function of the ABCC6 gene?

The ABCC6 gene provides instructions for making a protein called multidrug resistance-associated protein 6 (MRP6, also known as the ABCC6 protein). This protein is found primarily in the liver and kidneys, with small amounts in other tissues such as the skin, stomach, blood vessels, and eyes. The MRP6 protein belongs to a group of proteins that transport molecules across cell membranes; however, little is known about the substances transported by MRP6.

Some studies suggest that MRP6 stimulates the release of a molecule called adenosine triphosphate (ATP) from cells through an unknown mechanism. This ATP is quickly broken down into other molecules called adenosine monophosphate (AMP) and pyrophosphate. Pyrophosphate helps control deposition of calcium (calcification) and other minerals (mineralization) in the body.

Other studies suggest that MRP6 transports a substance that is involved in the breakdown of ATP. This unidentified substance is thought to help prevent mineralization of tissues.

Does the ABCC6 gene share characteristics with other genes?

The ABCC6 gene belongs to a family of genes called ABC (ATP-binding cassette transporters). It also 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 ABCC6 gene related to health conditions?

generalized arterial calcification of infancy - caused by mutations in the ABCC6 gene

At least 13 mutations in the ABCC6 gene have been identified in individuals with generalized arterial calcification of infancy (GACI), a life-threatening disorder characterized by abnormal calcification in the blood vessels that carry blood from the heart to the rest of the body (the arteries). Most of these mutations have also been identified in people with pseudoxanthoma elasticum (PXE), described below. These mutations lead to an absent or nonfunctional MRP6 protein. It is unclear how a lack of properly functioning MRP6 protein leads to GACI. This shortage may impair the release of ATP from cells. As a result, little pyrophosphate is produced and calcium accumulates in the blood vessels and other tissues affected by GACI. Alternatively, a lack of functioning MRP6 may impair the transport of a substance that would normally prevent mineralization, leading to the abnormal accumulation of calcium characteristic of GACI. It is not known why the same mutations can cause GACI in some individuals and PXE in others.

pseudoxanthoma elasticum - caused by mutations in the ABCC6 gene

More than 200 ABCC6 gene mutations that cause pseudoxanthoma elasticum (PXE) have been identified. PXE is a condition characterized by abnormal accumulation of calcium and other minerals in elastic fibers, a component of connective tissues that provide strength and flexibility to structures throughout the body. The ABCC6 gene mutations involved in this condition lead to an absence of MRP6 protein or an altered protein that does not function properly. The most common mutation in the United States, found in about 28 percent of people with PXE, deletes part of the ABCC6 gene. (This mutation is written as Ex23_29del.)

It is unclear how loss of MRP6 function leads to PXE. As in GACI (described above), this loss may impair the release of ATP or the transport of a substance that normally prevents mineralization. Without MRP6 function, calcium and other minerals accumulate in elastic fibers of the skin, eyes, blood vessels and other tissues affected by PXE.

Where is the ABCC6 gene located?

Cytogenetic Location: 16p13.1

Molecular Location on chromosome 16: base pairs 16,149,564 to 16,223,470

The ABCC6 gene is located on the short (p) arm of chromosome 16 at position 13.1.

The ABCC6 gene is located on the short (p) arm of chromosome 16 at position 13.1.

More precisely, the ABCC6 gene is located from base pair 16,149,564 to base pair 16,223,470 on chromosome 16.

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 ABCC6?

You and your healthcare professional may find the following resources about ABCC6 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 ABCC6 gene or gene products?

  • ABC34
  • anthracycline resistance-associated protein
  • ARA
  • EST349056
  • MLP1
  • MOAT-E
  • MRP6
  • MRP6_HUMAN
  • multidrug resistance-associated protein 6
  • multispecific organic anion transporter-E

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 ABCC6?

adenosine triphosphate ; anion ; arteries ; ATP ; breakdown ; calcification ; calcium ; cell ; elastic ; gene ; molecule ; mutation ; protein ; stomach

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

References

  • OMIM: ATP-BINDING CASSETTE, SUBFAMILY C, MEMBER 6 (http://omim.org/entry/603234)
  • Bercovitch L, Terry P. Pseudoxanthoma elasticum 2004. J Am Acad Dermatol. 2004 Jul;51(1 Suppl):S13-4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15243491?dopt=Abstract)
  • Bergen AA, Plomp AS, Schuurman EJ, Terry S, Breuning M, Dauwerse H, Swart J, Kool M, van Soest S, Baas F, ten Brink JB, de Jong PT. Mutations in ABCC6 cause pseudoxanthoma elasticum. Nat Genet. 2000 Jun;25(2):228-31. (http://www.ncbi.nlm.nih.gov/pubmed/10835643?dopt=Abstract)
  • Chassaing N, Martin L, Calvas P, Le Bert M, Hovnanian A. Pseudoxanthoma elasticum: a clinical, pathophysiological and genetic update including 11 novel ABCC6 mutations. J Med Genet. 2005 Dec;42(12):881-92. Epub 2005 May 13. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15894595?dopt=Abstract)
  • Dabisch-Ruthe M, Kuzaj P, Götting C, Knabbe C, Hendig D. Pyrophosphates as a major inhibitor of matrix calcification in Pseudoxanthoma elasticum. J Dermatol Sci. 2014 Aug;75(2):109-20. doi: 10.1016/j.jdermsci.2014.04.015. Epub 2014 May 17. (http://www.ncbi.nlm.nih.gov/pubmed/24907773?dopt=Abstract)
  • Gene Review: Generalized Arterial Calcification of Infancy (http://www.ncbi.nlm.nih.gov/books/NBK253403)
  • Gene Review: Pseudoxanthoma Elasticum (http://www.ncbi.nlm.nih.gov/books/NBK1113)
  • Hendig D, Schulz V, Arndt M, Szliska C, Kleesiek K, Götting C. Role of serum fetuin-A, a major inhibitor of systemic calcification, in pseudoxanthoma elasticum. Clin Chem. 2006 Feb;52(2):227-34. Epub 2005 Dec 29. (http://www.ncbi.nlm.nih.gov/pubmed/16384891?dopt=Abstract)
  • Hu X, Plomp A, Wijnholds J, Ten Brink J, van Soest S, van den Born LI, Leys A, Peek R, de Jong PT, Bergen AA. ABCC6/MRP6 mutations: further insight into the molecular pathology of pseudoxanthoma elasticum. Eur J Hum Genet. 2003 Mar;11(3):215-24. (http://www.ncbi.nlm.nih.gov/pubmed/12673275?dopt=Abstract)
  • Hu X, Plomp AS, van Soest S, Wijnholds J, de Jong PT, Bergen AA. Pseudoxanthoma elasticum: a clinical, histopathological, and molecular update. Surv Ophthalmol. 2003 Jul-Aug;48(4):424-38. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12850230?dopt=Abstract)
  • Iliás A, Urbán Z, Seidl TL, Le Saux O, Sinkó E, Boyd CD, Sarkadi B, Váradi A. Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6). J Biol Chem. 2002 May 10;277(19):16860-7. Epub 2002 Mar 5. (http://www.ncbi.nlm.nih.gov/pubmed/11880368?dopt=Abstract)
  • Jansen RS, Duijst S, Mahakena S, Sommer D, Szeri F, Váradi A, Plomp A, Bergen AA, Oude Elferink RP, Borst P, van de Wetering K. ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report. Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1985-9. doi: 10.1161/ATVBAHA.114.304017. Epub 2014 Jun 26. (http://www.ncbi.nlm.nih.gov/pubmed/24969777?dopt=Abstract)
  • Jansen RS, Küçükosmanoglu A, de Haas M, Sapthu S, Otero JA, Hegman IE, Bergen AA, Gorgels TG, Borst P, van de Wetering K. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20206-11. doi: 10.1073/pnas.1319582110. Epub 2013 Nov 25. (http://www.ncbi.nlm.nih.gov/pubmed/24277820?dopt=Abstract)
  • Le Saux O, Beck K, Sachsinger C, Silvestri C, Treiber C, Göring HH, Johnson EW, De Paepe A, Pope FM, Pasquali-Ronchetti I, Bercovitch L, Marais AS, Viljoen DL, Terry SF, Boyd CD. A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum. Am J Hum Genet. 2001 Oct;69(4):749-64. Epub 2001 Aug 31. Erratum in: Am J Hum Genet 2002 Aug;71(2):448. Am J Hum Genet 2001 Dec;69(6):1413. (http://www.ncbi.nlm.nih.gov/pubmed/11536079?dopt=Abstract)
  • Li Q, Brodsky JL, Conlin LK, Pawel B, Glatz AC, Gafni RI, Schurgers L, Uitto J, Hakonarson H, Deardorff MA, Levine MA. Mutations in the ABCC6 gene as a cause of generalized arterial calcification of infancy: genotypic overlap with pseudoxanthoma elasticum. J Invest Dermatol. 2014 Mar;134(3):658-65. doi: 10.1038/jid.2013.370. Epub 2013 Sep 5. (http://www.ncbi.nlm.nih.gov/pubmed/24008425?dopt=Abstract)
  • Markello TC, Pak LK, St Hilaire C, Dorward H, Ziegler SG, Chen MY, Chaganti K, Nussbaum RL, Boehm M, Gahl WA. Vascular pathology of medial arterial calcifications in NT5E deficiency: implications for the role of adenosine in pseudoxanthoma elasticum. Mol Genet Metab. 2011 May;103(1):44-50. doi: 10.1016/j.ymgme.2011.01.018. Epub 2011 Feb 3. (http://www.ncbi.nlm.nih.gov/pubmed/21371928?dopt=Abstract)
  • Matsuzaki Y, Nakano A, Jiang QJ, Pulkkinen L, Uitto J. Tissue-specific expression of the ABCC6 gene. J Invest Dermatol. 2005 Nov;125(5):900-5. (http://www.ncbi.nlm.nih.gov/pubmed/16297187?dopt=Abstract)
  • Miksch S, Lumsden A, Guenther UP, Foernzler D, Christen-Zäch S, Daugherty C, Ramesar RK, Lebwohl M, Hohl D, Neldner KH, Lindpaintner K, Richards RI, Struk B. Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6. Hum Mutat. 2005 Sep;26(3):235-48. (http://www.ncbi.nlm.nih.gov/pubmed/16086317?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/368)
  • Nitschke Y, Baujat G, Botschen U, Wittkampf T, du Moulin M, Stella J, Le Merrer M, Guest G, Lambot K, Tazarourte-Pinturier MF, Chassaing N, Roche O, Feenstra I, Loechner K, Deshpande C, Garber SJ, Chikarmane R, Steinmann B, Shahinyan T, Martorell L, Davies J, Smith WE, Kahler SG, McCulloch M, Wraige E, Loidi L, Höhne W, Martin L, Hadj-Rabia S, Terkeltaub R, Rutsch F. Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. Am J Hum Genet. 2012 Jan 13;90(1):25-39. doi: 10.1016/j.ajhg.2011.11.020. Epub 2011 Dec 29. (http://www.ncbi.nlm.nih.gov/pubmed/22209248?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: January 2015
Published: February 23, 2015