ArticleThe Journal of biological chemistry2016
Inactivation of Tm6sf2, a Gene Defective in Fatty Liver Disease, Impairs Lipidation but Not Secretion of Very Low Density Lipoproteins.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 4 of them syntheses that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
132 citing papers in PubMed, 4 syntheses or guidelines pooled it, 218 citations in OpenAlex.
- Meta-GWAS of PCSK9 levels detects two novel loci at APOB and TM6SF2.Human molecular genetics · 2022Pooled it
- TM6SF2 rs58542926 is related to hepatic steatosis, fibrosis and serum lipids both in adults and children: A meta-analysis.Frontiers in endocrinology · 2022Pooled it
- The effect of the TM6SF2 E167K variant on liver steatosis and fibrosis in patients with chronic hepatitis C: a meta-analysis.Scientific reports · 2017Pooled it
- Definitions of Normal Liver Fat and the Association of Insulin Sensitivity with Acquired and Genetic NAFLD-A Systematic Review.International journal of molecular sciences · 2016Pooled it
- Increased Genetic Risk for β-Cell Failure Is Associated With β-Cell Function Decline in People With Prediabetes.Diabetes · 2024Trial
- Hepatic Fat in Participants With and Without Incident Diabetes in the Diabetes Prevention Program Outcome Study.The Journal of clinical endocrinology and metabolism · 2021Trial
- Vitamin E absorption and kinetics in healthy women, as modulated by food and by fat, studied using 2 deuterium-labeled α-tocopherols in a 3-phase crossover design.The American journal of clinical nutrition · 2019Trial
- TM6SF2 overexpression suppresses the proliferation and promotes apoptosis of human hepatocellular carcinoma cells.Oncology reports · 2026Article
- Beyond Fat: Reframing MASLD Through Genetics, Clonal Biology, and Precision Hepatology.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Genome-wide association and polygenic risk score analyses of MASLD-related hepatic steatosis severity in a Taiwanese Han population.Cell & bioscience · 2026Article
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- Germline mutations and somatic mosaicism in steatotic liver diseases and related liver carcinogenesis.Nature reviews. Gastroenterology & hepatology · 2026Review
- Paediatric metabolic dysfunction-associated steatotic liver disease (MASLD): a growing health concern in the age of childhood obesity.BMJ paediatrics open · 2026Review
- Balancing cholesterol metabolism in the liver and gut: perspectives in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- MAFLD: a ferroptotic disease.Trends in molecular medicine · 2026Review
- Triglyceride-lowering therapies for hepatic steatosis: mechanisms, efficacy, and clinical perspectives.Frontiers in pharmacology · 2026Review
- Modeling Transmembrane 6 Superfamily Member 2 p.Glu167Lys-associated Steatotic Liver Disease Using Androgen-treated Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells.Gastro hep advances · 2026Article
- Genetics and epigenetics in tumor necrosis factor-alpha (Frontiers in medicine · 2026Article
- Human genetics of steatotic liver disease: insights into insulin resistance and lipid metabolism.Nature metabolism · 2025Review
- Somatic mutations in TBX3 promote hepatic clonal expansion by accelerating VLDL secretion.The Journal of clinical investigation · 2025Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
A missense mutation (E167K) in TM6SF2 (transmembrane 6 superfamily member 2), a polytopic protein of unknown function, is associated with the full spectrum of fatty liver disease. To investigate the role of TM6SF2 in hepatic triglyceride (TG) metabolism, we inactivated the gene in mice. Chronic inactivation of Tm6sf2 in mice is associated with hepatic steatosis, hypocholesterolemia, and transaminitis, thus recapitulating the phenotype observed in humans. No dietary challenge was required to elicit the phenotype. Immunocytochemical and cell fractionation studies revealed that TM6SF2 was present in the endoplasmic reticulum and Golgi complex, whereas the excess neutral lipids in the Tm6sf2(-/-) mice were located in lipid droplets. Plasma VLDL-TG levels were reduced in the KO animals due to a 3-fold decrease in VLDL-TG secretion rate without any associated reduction in hepatic apoB secretion. Both VLDL particle size and plasma cholesterol levels were significantly reduced in KO mice. Despite levels of TM6SF2 protein being 10-fold higher in the small intestine than in the liver, dietary lipid absorption was only modestly reduced in the KO mice. Our data, taken together, reveal that TM6SF2 is required to mobilize neutral lipids for VLDL assembly but is not required for secretion of apoB-containing lipoproteins. Despite TM6SF2 being located in the endoplasmic reticulum and Golgi complex, the lipids that accumulate in its absence reside in lipid droplets.
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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 Socratic graph.