ABCC2 p.R393W variant contributes to Dubin-Johnson syndrome by targeting MRP2 to proteasome degradation.

ABSTRACT:

Background

Dubin-Johnson syndrome (DJS), a rare autosomal recessive liver condition, is caused by biallelic loss-of-function mutations of the ABCC2 gene. This study aimed to investigate genetic variations in the drug efflux transporter ABCC2 (MRP2) gene in patients with DJS and to characterise the expression and mechanism of the ABCC2 gene variant.

Methods

Trio whole exome sequencing was performed in the family to identify the genetic causes. Bioinformatics analysis was performed to assess pathogenicity. In in vitro experiments, site-directed mutagenesis was used to introduce ABCC2 variants in constructs then expressed in HEK293T, HuH-7 and HepG2 cell lines. The expression of total and cell membrane MRP2 was quantified in cells expressing t

SUBMITTER: Sun RY 

PROVIDER: S-EPMC11770467 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature