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ABCB4 gene
URL of this page: https://medlineplus.gov/genetics/gene/abcb4/

ABCB4 gene

ATP binding cassette subfamily B member 4

Normal Function

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. The protein essentially flips the phospholipids from the inside to the outside of the cells. The protein then releases the phospholipids into a digestive fluid called bile. Outside the liver cells, in the bile duct, phospholipids attach (bind) to bile acids, which are the component of bile that digests fats. Large amounts of bile acids are potentially harmful to cells. When bile acids are bound to phospholipids, they are less toxic.

Health Conditions Related to Genetic Changes

Progressive familial intrahepatic cholestasis

Several variants (also called mutations) in the ABCB4 gene have been found to cause a severe form of liver disease called progressive familial intrahepatic cholestasis type 3 (PFIC3).  The signs and symptoms of PFIC3 often appear in early childhood.  PFIC3 causes progressive liver disease, which often leads to liver failure. Affected individuals have a variant in both copies of the ABCB4 gene. Variants that cause the cell to produce short, nonfunctional proteins or no proteins at all tend to be associated with more severe liver disease that appears earlier in life. ABCB4 gene variants that cause PFIC3 impair the movement of phospholipids across cell membranes, leading to a lack of phospholipids to bind to bile acids. A buildup of free bile acids damages liver cells, which causes the signs and symptoms of liver disease.

More About This Health Condition

Intrahepatic cholestasis of pregnancy

Pregnant people with variants in the ABCB4 gene are at risk of developing a condition called intrahepatic cholestasis of pregnancy. Affected people typically develop impaired bile secretion and severe itching during the second half of pregnancy. These features usually disappear after the baby is born.

Many of the variants in the ABCB4 gene that have been found in people with intrahepatic cholestasis of pregnancy cause the substitution of one protein building block (amino acid) for another. A few variants cause the cell to produce an abnormally short protein. Normally, enough protein is still available to move an adequate amount of phospholipids out of liver cells to bind to bile acids. The added stress on the liver during pregnancy, however, contributes to the buildup of bile acids.

When there are not enough phospholipids to bind to bile acids, the bile acids can build up to toxic levels and impair liver function, including the regulation of bile flow. Problems with bile flow lead to the signs and symptoms of intrahepatic cholestasis of pregnancy. Additional factors, such as increased hormone levels during pregnancy, are thought to contribute to the risk of developing this complex disorder.

More About This Health Condition

Other disorders

Variants 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 (known as gallstones) in the gallbladder or bile ducts. In people with LPAC, gallstones usually occur 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 the gallbladder is removed.

It is thought that the variants 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.

Other Names for This Gene

  • ABC21
  • ATP-binding cassette, sub-family B (MDR/TAP), member 4
  • ATP-binding cassette, subfamily B, member 4
  • GBD1
  • ICP3
  • MDR3
  • multidrug resistance 3
  • P-glycoprotein 3
  • PFIC-3
  • PGY3

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Bacq Y, Gendrot C, Perrotin F, Lefrou L, Chretien 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. Citation on PubMed
  • 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. Citation on PubMed or Free article on PubMed Central
  • 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. Citation on PubMed
  • 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. doi: 10.1038/sj.ejhg.5201908. Epub 2007 Aug 29. Citation on PubMed
  • Dixon PH, Sambrotta M, Chambers J, Taylor-Harris P, Syngelaki A, Nicolaides K, Knisely AS, Thompson RJ, Williamson C. An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy. Sci Rep. 2017 Sep 18;7(1):11823. doi: 10.1038/s41598-017-11626-x. Citation on PubMed
  • 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. doi: 10.1093/hmg/9.8.1209. Citation on PubMed
  • 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. doi: 10.1016/j.dld.2007.10.016. Epub 2007 Dec 20. Citation on PubMed
  • Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol. 2009 May 7;15(17):2049-66. doi: 10.3748/wjg.15.2049. Citation on PubMed or Free article on PubMed Central
  • Groen A, Romero MR, Kunne C, Hoosdally SJ, Dixon PH, Wooding C, Williamson C, Seppen J, Van den Oever K, Mok KS, Paulusma CC, Linton KJ, Oude Elferink RP. Complementary functions of the flippase ATP8B1 and the floppase ABCB4 in maintaining canalicular membrane integrity. Gastroenterology. 2011 Nov;141(5):1927-37.e1-4. doi: 10.1053/j.gastro.2011.07.042. Epub 2011 Aug 4. Citation on PubMed
  • Jansen PL, Sturm E. Genetic cholestasis, causes and consequences for hepatobiliary transport. Liver Int. 2003 Oct;23(5):315-22. doi: 10.1034/j.1478-3231.2003.00856.x. Citation on PubMed
  • 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. doi: 10.1016/j.jhep.2005.03.017. No abstract available. Citation on PubMed
  • 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. doi: 10.1016/s0016-5085(03)00898-9. Citation on PubMed
  • 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. doi: 10.1186/1750-1172-2-29. Citation on PubMed or Free article on PubMed Central
  • Zhu B, Yin P, Ma Z, Ma Y, Zhang H, Kong H, Zhu Y. Characteristics of bile acids metabolism profile in the second and third trimesters of normal pregnancy. Metabolism. 2019 Jun;95:77-83. doi: 10.1016/j.metabol.2019.04.004. Epub 2019 Apr 5. Citation on PubMed

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