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Genetics Home Reference: your guide to understanding genetic conditions
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ABCB4

Reviewed July 2012

What is the official name of the ABCB4 gene?

The official name of this gene is “ATP-binding cassette, sub-family B (MDR/TAP), member 4.”

ABCB4 is the gene's official symbol. The ABCB4 gene is also known by other names, listed below.

What is the normal function of the ABCB4 gene?

The ABCB4 gene (also known as MDR3) provides instructions for making a protein that helps move certain fats called phospholipids across the membranes of liver cells and release the phospholipids into a digestive fluid called bile. Outside the liver cells, phospholipids attach (bind) to bile acids, which are a component of bile that digest fats. Large amounts of bile acids are potentially harmful to cells; when they are bound to phospholipids, bile acids are less toxic.

Does the ABCB4 gene share characteristics with other genes?

The ABCB4 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 ABCB4 gene related to health conditions?

progressive familial intrahepatic cholestasis - caused by mutations in the ABCB4 gene

More than 45 mutations in the ABCB4 gene have been found to cause a severe form of liver disease called progressive familial intrahepatic cholestasis type 3 (PFIC3) that usually leads to liver failure. Affected individuals have a mutation in both copies of the ABCB4 gene. Mutations that lead to the production of a short, nonfunctional protein or cause no protein to be produced tend to be associated with more severe liver disease that appears earlier in life. ABCB4 gene mutations that cause PFIC3 impair the movement of phospholipids across cell membranes, leading to a lack of phospholipids available to bind to bile acids. A buildup of free bile acids damages liver cells, which causes the signs and symptoms of liver disease.

intrahepatic cholestasis of pregnancy - associated with the ABCB4 gene

Women with an ABCB4 gene mutation are at risk of developing a condition called intrahepatic cholestasis of pregnancy. Affected women typically develop impaired bile secretion and severe itching during the third trimester of pregnancy, and these features disappear after the baby is born. A single mutation in the ABCB4 gene leads to a mild reduction of the ABCB4 protein. Under most circumstances, though, enough protein is available to move an adequate amount of phospholipids out of liver cells to bind to bile acids. Although the mechanism is unclear, the function of the remaining ABCB4 protein appears to be impaired during pregnancy, which may further reduce the movement of phospholipids into bile. The lack of phospholipids available to bind to bile acids leads to a buildup of toxic bile acids that can impair liver function, including the regulation of bile flow. Problems with bile flow lead to the signs and symptoms of intrahepatic cholestasis of pregnancy. Many factors, however, likely contribute to the risk of developing this complex disorder.

other disorders - associated with the ABCB4 gene

Mutations in the ABCB4 gene are also associated with a rare condition called low phospholipid-associated cholelithiasis (LPAC). This condition is characterized by the formation of small pebble-like deposits of cholesterol in the gallbladder or bile ducts (gallstones). In LPAC, gallstones usually occur in people before age 40, which is young for the appearance of gallstones. In addition, affected individuals may have an accumulation of small crystals of cholesterol (microlithiasis) or a material called biliary sludge in the bile ducts of the liver. Biliary sludge is made up of solid particles that are usually dissolved in bile, including cholesterol crystals and calcium salts. The gallstones, cholesterol crystals, or biliary sludge can cause symptoms, such as pain, fever, nausea, or inflammation of the pancreas (pancreatitis), that can recur even after removal of the gall bladder.

It is thought that mutations in the ABCB4 gene that are involved in LPAC impair the protein's ability to transfer phospholipids into bile. Because phospholipids help keep cholesterol dissolved in bile, the lack of phospholipids can result in the formation of gallstones or crystals from undissolved cholesterol.

Where is the ABCB4 gene located?

Cytogenetic Location: 7q21.1

Molecular Location on chromosome 7: base pairs 87,402,044 to 87,475,702

The ABCB4 gene is located on the long (q) arm of chromosome 7 at position 21.1.

The ABCB4 gene is located on the long (q) arm of chromosome 7 at position 21.1.

More precisely, the ABCB4 gene is located from base pair 87,402,044 to base pair 87,475,702 on chromosome 7.

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 ABCB4?

You and your healthcare professional may find the following resources about ABCB4 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 ABCB4 gene or gene products?

  • ATP-binding cassette, subfamily B, member 4
  • MDR3
  • MDR3_HUMAN
  • multidrug resistance protein 3
  • multiple drug resistance 3
  • PFIC-3
  • P glycoprotein 3/multiple drug resistance 3
  • P-glycoprotein-3/multiple drug resistance-3
  • PGY3

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 ABCB4?

acids ; ATP ; bile ; calcium ; cell ; cholesterol ; digestive ; familial ; fever ; gallbladder ; gene ; inflammation ; liver failure ; mutation ; pancreas ; pancreatitis ; phospholipid ; phospholipids ; protein ; secretion ; toxic

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 4 (http://omim.org/entry/171060)
  • Bacq Y, Gendrot C, Perrotin F, Lefrou L, Chrétien S, Vie-Buret V, Brechot MC, Andres CR. ABCB4 gene mutations and single-nucleotide polymorphisms in women with intrahepatic cholestasis of pregnancy. J Med Genet. 2009 Oct;46(10):711-5. doi: 10.1136/jmg.2009.067397. Epub 2009 Jul 6. (http://www.ncbi.nlm.nih.gov/pubmed/19584064?dopt=Abstract)
  • 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)
  • Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. The spectrum of liver diseases related to ABCB4 gene mutations: pathophysiology and clinical aspects. Semin Liver Dis. 2010 May;30(2):134-46. doi: 10.1055/s-0030-1253223. Epub 2010 Apr 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20422496?dopt=Abstract)
  • Degiorgio D, Colombo C, Seia M, Porcaro L, Costantino L, Zazzeron L, Bordo D, Coviello DA. Molecular characterization and structural implications of 25 new ABCB4 mutations in progressive familial intrahepatic cholestasis type 3 (PFIC3). Eur J Hum Genet. 2007 Dec;15(12):1230-8. Epub 2007 Aug 29. (http://www.ncbi.nlm.nih.gov/pubmed/17726488?dopt=Abstract)
  • Dixon PH, Weerasekera N, Linton KJ, Donaldson O, Chambers J, Egginton E, Weaver J, Nelson-Piercy C, de Swiet M, Warnes G, Elias E, Higgins CF, Johnston DG, McCarthy MI, Williamson C. Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy: evidence for a defect in protein trafficking. Hum Mol Genet. 2000 May 1;9(8):1209-17. (http://www.ncbi.nlm.nih.gov/pubmed/10767346?dopt=Abstract)
  • Floreani A, Carderi I, Paternoster D, Soardo G, Azzaroli F, Esposito W, Montagnani M, Marchesoni D, Variola A, Rosa Rizzotto E, Braghin C, Mazzella G. Hepatobiliary phospholipid transporter ABCB4, MDR3 gene variants in a large cohort of Italian women with intrahepatic cholestasis of pregnancy. Dig Liver Dis. 2008 May;40(5):366-70. Epub 2007 Dec 20. (http://www.ncbi.nlm.nih.gov/pubmed/18083082?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)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5244)
  • 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)
  • Rosmorduc O, Hermelin B, Boelle PY, Parc R, Taboury J, Poupon R. ABCB4 gene mutation-associated cholelithiasis in adults. Gastroenterology. 2003 Aug;125(2):452-9. (http://www.ncbi.nlm.nih.gov/pubmed/12891548?dopt=Abstract)
  • Rosmorduc O, Poupon R. Low phospholipid associated cholelithiasis: association with mutation in the MDR3/ABCB4 gene. Orphanet J Rare Dis. 2007 Jun 11;2:29. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17562004?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: July 2012
Published: December 16, 2014