The MASLD-causing E167K variant of TM6SF2 is degraded by the ubiquitin ligase RNF5
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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.
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The MASLD-causing E167K variant of TM6SF2 is degraded by the ubiquitin ligase RNF5 https://www.biorxiv.org/content/10.64898/2026.10.21.760790v1
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The MASLD-causing E167K variant of TM6SF2 is degraded by the ubiquitin ligase RNF5 https://www.biorxiv.org/content/10.64898/2026.10.21.760790v1
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