Similar Publications
ABCC2 p.R393W variant contributes to Dubin-Johnson syndrome by targeting MRP2 to proteasome degradation.
eGastroenterology
January 2024
Department of Pediatrics, The First Affiliated Hospital Medical University, Wenzhou, Zhejiang, China.
Background: Dubin-Johnson syndrome (DJS), a rare autosomal recessive liver condition, is caused by biallelic loss-of-function mutations of the gene. This study aimed to investigate genetic variations in the drug efflux transporter (MRP2) gene in patients with DJS and to characterise the expression and mechanism of the gene variant.
Methods: Trio whole exome sequencing was performed in the family to identify the genetic causes.
Patterns and unique features of infantile cholestasis among Arabs.
Front Pediatr
July 2024
College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Background: Most of the literature on infantile cholestasis (IC) originated from Caucasian and Asian populations. The differential diagnosis of IC is very broad, and identification of etiology is challenging to clinicians because the list includes many entities with overlapping clinical, biochemical, and histological features. Thus, a structured, stepwise diagnostic approach is required to help early recognition and prompt evaluation and management of treatable causes of cholestasis.
View Article and Find Full Text PDFCase Report: A case of Dubin-Johnson syndrome in a newborn.
Front Pediatr
July 2024
Department of General Surgery, Hainan Women and Children's Medical Center, Hainan Women and Children's Medical Center, Haikou, Hainan, China.
Background: Dubin-Johnson Syndrome (DJS) is a rare autosomal recessive genetic disorder, with most cases presenting in adolescence, but rare in newborns.
Objective: To investigate the clinical characteristics and treatment outcomes of DJS in a newborn.
Methods: We present the clinical features of a newborn diagnosed with DJS through molecular genetic testing.
Article Synopsis
- MRP2 is an important protein that helps export substances out of liver cells and can affect how cancer treatments work; its dysfunction is linked to Dubin-Johnson Syndrome and increased liver damage risk from certain drugs.
- Researchers used cryogenic electron microscopy to visualize MRP2 in three different forms: autoinhibited, substrate-bound, and ATP-bound, demonstrating that it operates through ATP-driven changes in shape.
- The structure analysis shows that MRP2 has a regulatory domain that selectively allows certain substrates to initiate transport, helping to explain its role in multidrug resistance by recognizing a variety of compounds.
Structural basis for the modulation of MRP2 activity by phosphorylation and drugs.
Nat Commun
March 2024
Department of Life Sciences, Imperial College London, SW7 2AZ, London, UK.
Multidrug resistance-associated protein 2 (MRP2/ABCC2) is a polyspecific efflux transporter of organic anions expressed in hepatocyte canalicular membranes. MRP2 dysfunction, in Dubin-Johnson syndrome or by off-target inhibition, for example by the uricosuric drug probenecid, elevates circulating bilirubin glucuronide and is a cause of jaundice. Here, we determine the cryo-EM structure of rat Mrp2 (rMrp2) in an autoinhibited state and in complex with probenecid.
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