ArticleHuman molecular genetics2017
Hepatic Tm6sf2 overexpression affects cellular ApoB-trafficking, plasma lipid levels, hepatic steatosis and atherosclerosis.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- TM6SF2 rs58542926 is related to hepatic steatosis, fibrosis and serum lipids both in adults and children: A meta-analysis.Frontiers in endocrinology · 2022Pooled it
- Autophagy in MASLD: A Metabolic and Precision Medicine Perspective.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Molecular mechanisms and pathogenesis of MASH.Nature · 2026Review
- Environmentally relevant lanthanum chloride exposure induces hepatic steatosis in zebrafish larvae via PPARα-dependent ApoB suppression.Communications biology · 2026Article
- Rethinking the hepatoprotective potential of vegetarian diets in dysfunction-associated steatotic liver disease/metabolic-associated fatty liver disease: a critical narrative review.Frontiers in nutrition · 2026Review
- Human-induced pluripotent stem cell-based hepatic modeling of lipid metabolism-associated TM6SF2-E167K variant.Hepatology (Baltimore, Md.) · 2025Article
- Deep metabolic phenotyping of humans with protein-altering variants inJHEP reports : innovation in hepatology · 2025Article
- Molecular Regulation and Therapeutic Targeting of VLDL Production in Cardiometabolic Disease.Cellular and molecular gastroenterology and hepatology · 2025Review
- TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD.Clinical and molecular hepatology · 2024Article
- VLDL Biogenesis and Secretion: It Takes a Village.Circulation research · 2024Review
- Mechanisms Behind NAFLD: a System Genetics Perspective.Current atherosclerosis reports · 2023Review
- Insulin Regulation of Hepatic Lipid Homeostasis.Comprehensive Physiology · 2023Review
- Article
- Exome-wide association analysis of CT imaging-derived hepatic fat in a medical biobank.Cell reports. Medicine · 2022Article
- MyeloidCells · 2022Article
- Mechanism and therapeutic strategy of hepaticWorld journal of gastroenterology · 2022Article
- The Role of Insulin Resistance in Fueling NAFLD Pathogenesis: From Molecular Mechanisms to Clinical Implications.Journal of clinical medicine · 2022Review
- TM6SF2: A Novel Genetic Player in Nonalcoholic Fatty Liver and Cardiovascular Disease.Hepatology communications · 2022Review
- Activation of Liver mTORC1 Protects Against NASH via Dual Regulation of VLDL-TAG Secretion and De Novo Lipogenesis.Cellular and molecular gastroenterology and hepatology · 2022Article
- Nonalcoholic Fatty Liver Disease (NAFLD): Pathogenesis and Noninvasive Diagnosis.Biomedicines · 2021Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
The human transmembrane 6 superfamily member 2 (TM6SF2) gene has been implicated in plasma lipoprotein metabolism, alcoholic and non-alcoholic fatty liver disease and myocardial infarction in multiple genome-wide association studies. To investigate the role of Tm6sf2 in metabolic homeostasis, we generated mice with elevated expression using adeno-associated virus (AAV)-mediated gene delivery. Hepatic overexpression of mouse Tm6sf2 resulted in phenotypes previously observed in Tm6sf2-deficient mice including reduced plasma lipid levels, diminished hepatic triglycerides secretion and increased hepatosteatosis. Furthermore, increased hepatic Tm6sf2 expression protected against the development of atherosclerosis in LDL-receptor/ApoB48-deficient mice. In cultured human hepatocytes, Tm6sf2 overexpression reduced apolipoprotein B secretion and resulted in its accumulation within the endoplasmic reticulum (ER) suggesting impaired ER-to-Golgi trafficking of pre-very low-density lipoprotein (VLDL) particles. Analysis of two metabolic trait-associated coding polymorphisms in the human TM6SF2 gene (rs58542926 and rs187429064) revealed that both variants impact TM6SF2 expression by affecting the rate of protein turnover. These data demonstrate that rs58542926 (E167K) and rs187429064 (L156P) are functional variants and suggest that they influence metabolic traits through altered TM6SF2 protein stability. Taken together, our results indicate that cellular Tm6sf2 level is an important determinant of VLDL metabolism and further implicate TM6SF2 as a causative gene underlying metabolic disease and trait associations at the 19p13.11 locus.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.