Skip navigation

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

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 transport certain fat molecules (phospholipids) across the membranes of liver cells. The protein moves phospholipids from the inside to the outside of the cell membrane. The ABCB4 protein belongs to a class of proteins called floppases.

The ABCB4 proteins release the phospholipids into a digestive fluid called bile, which is made and released by the liver. Phospholipids help keep cholesterol dissolved in bile so that it can be safely transported. Phospholipids also attach to a component of bile called bile acids. Large amounts of bile acids are potentially harmful to cells. However, when bile acids are bound to phospholipids, they are less toxic. 

Health Conditions Related to Genetic Changes

Intrahepatic cholestasis of pregnancy

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the ABCB4 gene have been found to cause a condition called intrahepatic cholestasis of pregnancy (ICP). Signs and symptoms of ICP typically include impaired bile secretion and severe itching during the second half of pregnancy. These features usually disappear after the baby is born. 

Many of the pathogenic variants in the ABCB4 gene that have been associated with ICP cause the substitution of one protein building block (amino acid) for another. A few variants cause the cell to produce an abnormally short version of the ABCB4 protein. Normally, enough ABCB4 proteins are 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 ICP. 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

Progressive familial intrahepatic cholestasis

Pathogenic variants in the ABCB4 gene have been found to cause a severe form of progressive familial intrahepatic cholestasis called MDR3 deficiency (formerly known as PFIC3). The signs and symptoms of MDR3 deficiency often appear in early childhood. MDR3 deficiency causes progressive liver disease, which often leads to liver failure. The pathogenic variants in the ABCB4 gene that cause the cell to produce short, nonfunctional versions of the ABCB4 protein or no proteins at all tend to be associated with more severe liver disease that appears earlier in life. The pathogenic variants that cause MDR3 deficiency impair the movement of phospholipids across cell membranes, which means that there are fewer phospholipids to bind to bile acids. A buildup of bile acids damages liver cells, leading to cholestasis and liver disease. 

More About This Health Condition

Other disorders

Pathogenic 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 in the bile ducts or gallbladder (gallstones). In people with LPAC, gallstones usually occur before age 40. In addition to gallstones, 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, including cholesterol crystals and calcium salts. The gallstones, cholesterol crystals, or biliary sludge can cause pain, fever, nausea, inflammation of the pancreas (pancreatitis), and other symptoms. It is thought that the pathogenic variants in the ABCB4 gene that cause LPAC impair the protein's ability to transfer phospholipids into bile. Without phospholipids, cholesterol cannot be properly dissolved, leading to the formation of gallstones or crystals.

Pathogenic variants in the ABCB4 gene can also cause drug-induced cholestasis, a condition in which certain medications, such as antibiotics, can cause bile to build up in the liver. Drug-induced cholestasis is more likely to occur in people over the age of 60.

Other Names for This Gene

  • GBD1
  • PFIC-3

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

  • Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ. Systematic review of progressive familial intrahepatic cholestasis. Clin Res Hepatol Gastroenterol. 2019 Feb;43(1):20-36. doi: 10.1016/j.clinre.2018.07.010. Epub 2018 Sep 17. Citation on PubMed
  • Bull LN, Thompson RJ. Progressive Familial Intrahepatic Cholestasis. Clin Liver Dis. 2018 Nov;22(4):657-669. doi: 10.1016/j.cld.2018.06.003. Epub 2018 Aug 3. 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
  • 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
  • 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
  • Hassan S, Hertel P. Overview of Progressive Familial Intrahepatic Cholestasis. Clin Liver Dis. 2022 Aug;26(3):371-390. doi: 10.1016/j.cld.2022.03.003. 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, 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
  • Vitale G, Sciveres M, Mandato C, d'Adamo AP, Di Giorgio A. Genotypes and different clinical variants between children and adults in progressive familial intrahepatic cholestasis: a state-of-the-art review. Orphanet J Rare Dis. 2025 Feb 21;20(1):80. doi: 10.1186/s13023-025-03599-2. Citation on PubMed
  • Xie S, Wei S, Ma X, Wang R, He T, Zhang Z, Yang J, Wang J, Chang L, Jing M, Li H, Zhou X, Zhao Y. Genetic alterations and molecular mechanisms underlying hereditary intrahepatic cholestasis. Front Pharmacol. 2023 May 31;14:1173542. doi: 10.3389/fphar.2023.1173542. eCollection 2023. Citation on PubMed
  • 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
  • Zollner J, Williamson C, Dixon PH. Genetic issues in ICP. Obstet Med. 2024 Sep;17(3):157-161. doi: 10.1177/1753495X241263441. Epub 2024 Jul 26. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.