Correction of a Traffic-Defective Missense ABCB11 Variant Responsible for Progressive Familial Intrahepatic Cholestasis Type 2.

ABSTRACT: Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a severe hepatocellular cholestasis due to biallelic variations in the ABCB11 (ATP-binding cassette B11) gene encoding the canalicular bile salt export pump (BSEP). Some missense variants identified in patients with PFIC2 do not traffic properly to the canalicular membrane. However, 4-phenybutyrate (4-PB) has been shown in vitro to partially correct the mis-trafficking of selected variants, resulting in an improvement of the medical conditions of corresponding PFIC2 patients. Herein, we report the ability of 4-PB analogous or homologous drugs and of non-4-PB related chemical correctors to rescue the canalicular expression and the activity of the folding-defective Abcb11^R1128C variant. New compounds, either id

SUBMITTER: Lapalus M 

PROVIDER: S-EPMC12154090 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature