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Genetics Home Reference: your guide to understanding genetic conditions
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ABCB11

Reviewed June 2012

What is the official name of the ABCB11 gene?

The official name of this gene is “ATP-binding cassette, sub-family B (MDR/TAP), member 11.”

ABCB11 is the gene's official symbol. The ABCB11 gene is also known by other names, listed below.

What is the normal function of the ABCB11 gene?

The ABCB11 gene provides instructions for making a protein called the bile salt export pump (BSEP), which is found in the liver. Bile salts are a component of bile, which is used to digest fats. Bile salts are produced by liver cells and then transported out of the cell by BSEP to make bile. The release of bile salts from liver cells is critical for the normal secretion of bile.

Does the ABCB11 gene share characteristics with other genes?

The ABCB11 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 ABCB11 gene related to health conditions?

benign recurrent intrahepatic cholestasis - caused by mutations in the ABCB11 gene

Mutations in the ABCB11 gene can cause benign recurrent intrahepatic cholestasis type 2 (BRIC2). People with BRIC2 have occasional episodes of impaired bile secretion that lead to severe itching (pruritus) and yellowing of the skin and whites of the eyes (jaundice). On occasion, people with BRIC2 have later been diagnosed with a more severe condition called progressive familial intrahepatic cholestasis type 2 (described below) when their symptoms worsened.

Affected individuals have a mutation in both copies of the ABCB11 gene. Mutations in the ABCB11 gene that cause BRIC2 lead to a 40 to 50 percent reduction of bile salt transport. The resulting buildup of bile salts in the liver leads to the signs and symptoms of BRIC2. It is unclear what causes the episodes to begin or end.

progressive familial intrahepatic cholestasis - caused by mutations in the ABCB11 gene

More than 100 mutations in the ABCB11 gene have been found to cause a severe form of liver disease called progressive familial intrahepatic cholestasis type 2 (PFIC2) that usually leads to liver failure. Development of this condition requires a mutation in both copies of the ABCB11 gene. Mutations in the ABCB11 gene that cause PFIC2 result in a 70 percent reduction to complete absence of bile salt transport out of the liver. The lack of transport causes bile salts to build up in liver cells, leading to liver disease and its associated signs and symptoms.

Mutations that lead to the production of a short, nonfunctional protein or cause no protein to be produced tend to be associated with severe liver disease that appears earlier in life. People with no functional BSEP protein also seem to be at a greater risk of developing a type of liver cancer called hepatocellular carcinoma.

intrahepatic cholestasis of pregnancy - associated with the ABCB11 gene

Women with a change in the ABCB11 gene are at risk of developing a condition called intrahepatic cholestasis of pregnancy. Affected women typically develop impaired bile secretion (cholestasis) and pruritus during the third trimester of pregnancy, and these features disappear after the baby is born. A common variation (polymorphism) in the ABCB11 gene is found more often in women who develop this condition than women who do not. This variation leads to a change in a single protein building block (amino acid) in the BSEP protein. Specifically, the amino acid valine is replaced by the amino acid alanine at position 444 of the protein (written as V444A). This change leads to a reduction in the amount of BSEP protein in liver cells. In rare cases, an uncommon change (a mutation) in one copy of the ABCB11 gene is found in women with intrahepatic cholestasis of pregnancy. A single mutation in this gene increases the risk of developing intrahepatic cholestasis of pregnancy. These mutations likely reduce the amount or function of the BSEP protein.

In women with either type of genetic change, enough BSEP function remains for sufficient bile secretion under most circumstances. Studies show that the hormones estrogen and progesterone (and products formed during their breakdown), which are elevated during pregnancy, further reduce the function of BSEP, resulting in impaired bile secretion and the signs and symptoms of intrahepatic cholestasis of pregnancy. Many factors, however, likely contribute to the risk of developing this complex disorder.

Where is the ABCB11 gene located?

Cytogenetic Location: 2q24

Molecular Location on chromosome 2: base pairs 168,922,825 to 169,031,322

The ABCB11 gene is located on the long (q) arm of chromosome 2 at position 24.

The ABCB11 gene is located on the long (q) arm of chromosome 2 at position 24.

More precisely, the ABCB11 gene is located from base pair 168,922,825 to base pair 169,031,322 on chromosome 2.

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 ABCB11?

You and your healthcare professional may find the following resources about ABCB11 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 ABCB11 gene or gene products?

  • ABC16
  • ABCBB_HUMAN
  • bile salt export pump
  • BRIC2
  • BSEP
  • PFIC2
  • PFIC-2
  • progressive familial intrahepatic cholestasis 2
  • sister p-glycoprotein
  • SPGP

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 ABCB11?

alanine ; amino acid ; ATP ; benign ; bile ; breakdown ; cancer ; carcinoma ; cell ; familial ; gene ; hepatocellular carcinoma ; jaundice ; liver cancer ; liver failure ; mutation ; polymorphism ; progesterone ; protein ; secretion ; valine

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

References

  • OMIM: ATP-BINDING CASSETTE, SUBFAMILY B, MEMBER 11 (http://omim.org/entry/603201)
  • Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis. 2009 Jan 8;4:1. doi: 10.1186/1750-1172-4-1. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19133130?dopt=Abstract)
  • Dixon PH, van Mil SW, Chambers J, Strautnieks S, Thompson RJ, Lammert F, Kubitz R, Keitel V, Glantz A, Mattsson LA, Marschall HU, Molokhia M, Moore GE, Linton KJ, Williamson C. Contribution of variant alleles of ABCB11 to susceptibility to intrahepatic cholestasis of pregnancy. Gut. 2009 Apr;58(4):537-44. doi: 10.1136/gut.2008.159541. Epub 2008 Nov 5. (http://www.ncbi.nlm.nih.gov/pubmed/18987030?dopt=Abstract)
  • Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol. 2009 May 7;15(17):2049-66. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19418576?dopt=Abstract)
  • Jansen PL, Sturm E. Genetic cholestasis, causes and consequences for hepatobiliary transport. Liver Int. 2003 Oct;23(5):315-22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14708891?dopt=Abstract)
  • Kagawa T, Watanabe N, Mochizuki K, Numari A, Ikeno Y, Itoh J, Tanaka H, Arias IM, Mine T. Phenotypic differences in PFIC2 and BRIC2 correlate with protein stability of mutant Bsep and impaired taurocholate secretion in MDCK II cells. Am J Physiol Gastrointest Liver Physiol. 2008 Jan;294(1):G58-67. Epub 2007 Oct 18. (http://www.ncbi.nlm.nih.gov/pubmed/17947449?dopt=Abstract)
  • Lam P, Pearson CL, Soroka CJ, Xu S, Mennone A, Boyer JL. Levels of plasma membrane expression in progressive and benign mutations of the bile salt export pump (Bsep/Abcb11) correlate with severity of cholestatic diseases. Am J Physiol Cell Physiol. 2007 Nov;293(5):C1709-16. Epub 2007 Sep 13. (http://www.ncbi.nlm.nih.gov/pubmed/17855769?dopt=Abstract)
  • Lam P, Soroka CJ, Boyer JL. The bile salt export pump: clinical and experimental aspects of genetic and acquired cholestatic liver disease. Semin Liver Dis. 2010 May;30(2):125-33. doi: 10.1055/s-0030-1253222. Epub 2010 Apr 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20422495?dopt=Abstract)
  • Meier Y, Pauli-Magnus C, Zanger UM, Klein K, Schaeffeler E, Nussler AK, Nussler N, Eichelbaum M, Meier PJ, Stieger B. Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver. Hepatology. 2006 Jul;44(1):62-74. (http://www.ncbi.nlm.nih.gov/pubmed/16799996?dopt=Abstract)
  • Meier Y, Zodan T, Lang C, Zimmermann R, Kullak-Ublick GA, Meier PJ, Stieger B, Pauli-Magnus C. Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump. World J Gastroenterol. 2008 Jan 7;14(1):38-45. (http://www.ncbi.nlm.nih.gov/pubmed/18176959?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/8647)
  • Pauli-Magnus C, Stieger B, Meier Y, Kullak-Ublick GA, Meier PJ. Enterohepatic transport of bile salts and genetics of cholestasis. J Hepatol. 2005 Aug;43(2):342-57. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15975683?dopt=Abstract)
  • Strautnieks SS, Bull LN, Knisely AS, Kocoshis SA, Dahl N, Arnell H, Sokal E, Dahan K, Childs S, Ling V, Tanner MS, Kagalwalla AF, Németh A, Pawlowska J, Baker A, Mieli-Vergani G, Freimer NB, Gardiner RM, Thompson RJ. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet. 1998 Nov;20(3):233-8. (http://www.ncbi.nlm.nih.gov/pubmed/9806540?dopt=Abstract)
  • Strautnieks SS, Byrne JA, Pawlikowska L, Cebecauerová D, Rayner A, Dutton L, Meier Y, Antoniou A, Stieger B, Arnell H, Ozçay F, Al-Hussaini HF, Bassas AF, Verkade HJ, Fischler B, Németh A, Kotalová R, Shneider BL, Cielecka-Kuszyk J, McClean P, Whitington PF, Sokal E, Jirsa M, Wali SH, Jankowska I, Pawłowska J, Mieli-Vergani G, Knisely AS, Bull LN, Thompson RJ. Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families. Gastroenterology. 2008 Apr;134(4):1203-14. doi: 10.1053/j.gastro.2008.01.038. Epub 2008 Jan 18. (http://www.ncbi.nlm.nih.gov/pubmed/18395098?dopt=Abstract)
  • Thompson R, Strautnieks S. BSEP: function and role in progressive familial intrahepatic cholestasis. Semin Liver Dis. 2001 Nov;21(4):545-50. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11745042?dopt=Abstract)
  • Vallejo M, Briz O, Serrano MA, Monte MJ, Marin JJ. Potential role of trans-inhibition of the bile salt export pump by progesterone metabolites in the etiopathogenesis of intrahepatic cholestasis of pregnancy. J Hepatol. 2006 Jun;44(6):1150-7. Epub 2005 Nov 7. (http://www.ncbi.nlm.nih.gov/pubmed/16458994?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 2012
Published: October 20, 2014