Work

The MASLD-causing E167K variant of TM6SF2 is degraded by the ubiquitin ligase RNF5

Year: 2026

Type: preprint

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.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.64898/2026.10.21.760790

Authors: Emad Heidary Arash, Huimin Pan, Holger Willenbring

Institution: University of California, San Francisco

Language: English

Topic: Liver Disease Diagnosis and Treatment

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, University of California, San Francisco, Liver Center, University of California, San Francisco