ABCB4 Gene: Function, Mutations, and Associated Diseases | NCBI, UniProt, ClinVar

The ABCB4 gene encodes the multidrug resistance protein 3 (MDR3), a member of the ATP-binding cassette (ABC) transporter superfamily. MDR3 is primarily expressed in the canalicular membrane of hepatocytes and functions as a floppase that translocates phosphatidylcholine from the inner to the outer leaflet of the canalicular membrane, facilitating its secretion into bile. This phospholipid secretion is essential for micelle formation and protection of the biliary epithelium from detergent bile salts. Mutations in ABCB4 cause progressive familial intrahepatic cholestasis type 3 (PFIC3), low phospholipid-associated cholelithiasis (LPAC), and intrahepatic cholestasis of pregnancy (ICP).

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Bile secretion (KEGG hsa04976)

• ABC transporters (KEGG hsa02010)

• Phospholipid homeostasis (Reactome R-HSA-1483206)

MDR3 (ABCB4) is a 1279-amino acid transmembrane glycoprotein with two nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). It functions as a homodimer or heterodimer with other ABC transporters. The protein is localized to the canalicular membrane of hepatocytes and uses ATP hydrolysis to translocate phosphatidylcholine into bile. This activity is critical for biliary lipid secretion and protection against bile salt toxicity. Structural mutations in the NBDs or TMDs disrupt ATPase activity or substrate recognition, leading to cholestatic liver diseases.