The ATP-binding cassette 4 (''ABCB4'')
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
encodes multidrug resistance protein 3.
''ABCB4'' is associated with
progressive familial intrahepatic cholestasis
Progressive familial intrahepatic cholestasis (PFIC) is a group of Genetic disorder, familial cholestasis, cholestatic conditions caused by defects in bile, biliary Epithelium, epithelial transporters. The clinical presentation usually occurs firs ...
type 3 and
intrahepatic cholestasis of pregnancy
Intrahepatic cholestasis of pregnancy (ICP), also known as obstetric cholestasis, cholestasis of pregnancy, jaundice of pregnancy, and prurigo gravidarum, is a medical condition in which cholestasis occurs during pregnancy. It typically presents wi ...
.
The membrane-associated
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
encoded by this gene is a member of the superfamily of
ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This gene encodes a full transporter and member of the p-glycoprotein family of membrane proteins with phosphatidylcholine as its substrate (
flippase
Flippases are transmembrane lipid transporter proteins located in the cell membrane. They are responsible for aiding the movement of phospholipid molecules between the two layers, or leaflets, that comprise the membrane. This is called transverse ...
activity). The function of this protein has not yet been determined; however, it may involve transport of phospholipids from liver hepatocytes into bile. Alternative splicing of this gene results in several products of undetermined function.
Cancer
''ABCB4'' gene has been observed progressively downregulated in
human papillomavirus
Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and r ...
-positive
neoplastic keratinocytes derived from uterine cervical
preneoplastic lesions at different levels of malignancy.
For this reason, ABCB4 is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical
preneoplastic lesions progression.
Other conditions that have been associated with mutations in this gene include
low phospholipid associated cholelithiasis syndrome, high gamma glutamyl transferase intrahepatic cholestasis of pregnancy, chronic cholangiopathy and adult biliary fibrosis.
[Sticova E, Jirsa M (2019) ABCB4 disease: Many faces of one gene deficiency. Ann Hepatol ]
References
Further reading
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External links
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