bioRxivBiochemistryPreprint
The MASLD-causing E167K variant of TM6SF2 is degraded by the ubiquitin ligase RNF5
Abstract
The TM6SF2 E167K loss-of-function variant is one of the most penetrant genetic risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD), including progression to cirrhosis and hepatocellular carcinoma. Here we show that TM6SF2 E167K is recognized and degraded by the ER-associated degradation pathway, and identify RNF5 as the ubiquitin ligase tagging TM6SF2 E167K, providing a rational target for MASLD therapy.
- Citations
- 0
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Human Induced Pluripotent Stem Cell based Hepatic-Modeling of Lipid metabolism associated TM6SF2 E167K variant
L. A. P. Faccioli, Y. Sun, … A. Soto-Gutierrez·bioRxiv·Dec 18, 2023
- MTARC1 Regulates Lipid Droplet Degradation via Phospholipid Remodeling in Metabolic Fatty Liver Disease
- Induction of TFEB promotes Kupffer cell survival and reduces lipid accumulation and inflammation in MASLD
Mandy M. Chan, Sabine Daemen, … Joel D. Schilling·bioRxiv·Apr 19, 2025
- Perturbation of transmembrane 6 superfamily member 2 expression alters lipid metabolism in a human liver cell line
A. Pant, Y. Chen, … E. K. Speliotes·bioRxiv·Aug 4, 2021
- The Lipid Hydrolase ABHD6 is a Therapeutic Target in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-Related Hepatocellular Carcinoma
Danny Orabi, William J. Massey, … J. Mark Brown·bioRxiv·Jul 29, 2025
- TMPRSS6 Cleavage of β-Klotho Modulates FGF19 Signaling
Matthieu Lepage, Antoine Désilets, … Richard Leduc·bioRxiv·Aug 27, 2026