ABCB4 disease-causing variants S242R, S346I, T437I and T1077M significantly impair its function and display differential sensitivity to potentiators.

ABSTRACT: The hepato-canalicular adenosine triphosphate (ATP)-binding cassette transporter ABCB4/MDR3 is responsible of the secretion of phosphatidylcholine (PC) into bile. Variations in ABCB4 gene induce a spectrum of cholestatic liver diseases, the most severe form is progressive familial intrahepatic cholestasis type 3 (PFIC3). The purpose of our study was to investigate the impact and potential rescue of four ABCB4 missense variants identified in patients, two of which (T437I and T1077M) affect homologous amino acids in the Walker A motifs in the two nucleotide-binding sites NBS2 and NBS1, respectively and the other two (S242R and S346I) affect residues of the transmembrane helices 4 and 6, respectively. The functional role of the four amino acids was assessed by analysis of three-dimensional (3

SUBMITTER: Madry C 

PROVIDER: S-EPMC12739136 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature