Normal Function
The ATP8B1 gene (also known as FIC1) provides instructions for making a protein that is found throughout the body. The ATP8B1 protein transports certain fat molecules (phospholipids) from the outer surface of cell membranes to the inner surface of the membrane. The ATP8B1 protein belongs to a class of proteins called flippases.
Maintaining the proper distribution of phospholipids within liver cell membranes ensures that the cell can properly transport the components of a digestive fluid called bile, which is made and released by the liver. The ATP8B1 protein also helps protect liver cells from the damaging effects of bile acids, a major component of bile.
Health Conditions Related to Genetic Changes
Benign recurrent intrahepatic cholestasis
Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the ATP8B1 gene can cause benign recurrent intrahepatic cholestasis type 1 (BRIC1). Cholestasis is a condition that impairs the release of bile. People with BRIC1 typically have episodes of cholestasis. This can lead to severe itching (pruritus) and yellowing of the skin and the whites of the eyes (jaundice). The pathogenic variants in the ATP8B1 gene that cause BRIC1 likely alter the structure or function of the ATP8B1 protein. Although it is not entirely clear how these changes cause cholestasis, researchers suspect that these variants impair the membrane's ability to transport bile components across the cell membrane. As a result, bile acids can build up inside liver cells, damaging the cells and causing the signs and symptoms of BRIC1.
Many researchers now consider BRIC1 to be a mild version of a form of progressive familial intrahepatic cholestasis (PFIC) known as FIC1 deficiency rather than a separate disorder. PFIC is a group of disorders that cause chronic, progressive liver disease. BRIC1 is often called recurrent intrahepatic cholestasis since some people with BRIC1 develop liver disease that worsens over time.
More About This Health ConditionProgressive familial intrahepatic cholestasis
Pathogenic variants in the ATP8B1 gene have been found to cause a form of PFIC called FIC1 deficiency (formerly known as PIFC1). Many people with PFIC will eventually develop liver failure. People with FIC1 deficiency may also have signs and symptoms that affect other parts of the body, such as hearing loss, diarrhea, and short stature. The pathogenic variants in the ATP8B1 gene that cause FIC1 deficiency alter the structure or function of the ATP8B1 protein. Although it is not entirely clear how these changes cause cholestasis, researchers suspect that these variants impair the membrane's ability to transport bile components across the cell membrane. As a result, bile acids can build up inside liver cells, damaging the cells and causing the signs and symptoms of FIC1 deficiency. The ATP8B1 protein is found throughout the body, which could explain why people with FIC1 deficiency may also have hearing loss, diarrhea, and short stature.
More About This Health ConditionIntrahepatic cholestasis of pregnancy
MedlinePlus Genetics provides information about Intrahepatic cholestasis of pregnancy
More About This Health ConditionOther Names for This Gene
- PFIC
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Bull LN, Morotti R, Squires JE. ATP8B1 Deficiency. 2001 Oct 15 [updated 2021 Sep 9]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1297/ 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
- Cai SY, Gautam S, Nguyen T, Soroka CJ, Rahner C, Boyer JL. ATP8B1 deficiency disrupts the bile canalicular membrane bilayer structure in hepatocytes, but FXR expression and activity are maintained. Gastroenterology. 2009 Mar;136(3):1060-9. doi: 10.1053/j.gastro.2008.10.025. Epub 2008 Nov 1. Citation on PubMed or Free article on PubMed Central
- 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
- 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
- Paulusma CC, de Waart DR, Kunne C, Mok KS, Elferink RP. Activity of the bile salt export pump (ABCB11) is critically dependent on canalicular membrane cholesterol content. J Biol Chem. 2009 Apr 10;284(15):9947-54. doi: 10.1074/jbc.M808667200. Epub 2009 Feb 19. 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
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