ArticleJournal of hepatology2022
Rare ATG7 genetic variants predispose patients to severe fatty liver disease.
Article in Journal of hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Obesity facts · 2024Guideline
- Genetics of MASLD: a diabetes perspective.Diabetologia · 2026Review
- Autophagy in MASLD: A Metabolic and Precision Medicine Perspective.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- γ-GC mitigates MASLD by reducing CD36 palmitoylation and plasma membrane translocation mediated by AKT/KLF10/zDHHC7 axis.Nutrition & metabolism · 2026Article
- Current Understanding of CHIP's Immunobiological Footprint with A Focus on Gastrointestinal Disorders: A Review of the Literature.Current oncology reports · 2026Review
- Ginsenoside F1 ameliorates nonalcoholic fatty liver disease by activating the AMPK/PGC-1α pathway and autophagy.In vitro cellular & developmental biology. Animal · 2026Article
- Germline mutations and somatic mosaicism in steatotic liver diseases and related liver carcinogenesis.Nature reviews. Gastroenterology & hepatology · 2026Review
- Peptide hormones and bile acids shaping immune tolerance of the liver: implications and applications.Protein & cell · 2026Review
- Genetic modulators of metabolic dysfunction-associated steatotic liver disease (MASLD) and their epistatic interactions: from in vitro and animal models to clinical outcomes.BMC medical genomics · 2026Review
- Genetic Predisposition to MASLD: Potential for Therapeutic Management.International journal of molecular sciences · 2026Review
- IFNAR2 p.F8S Variant Associates with Severe COVID-19 and Adaptive Immune Cell Activation Modulation.International journal of molecular sciences · 2026Article
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- Biomarkers for early identification of metabolic dysfunction-associated steatotic liver disease (MASLD): a narrative review.Archives of medical science : AMS · 2026Article
- Autophagy in the liver.Autophagy reports · 2026Review
- Evaluation of the Immortalized Primary Human Hepatocyte Cell Line Fa2N-4 as a Model for Metabolic Dysfunction-Associated Steatotic Liver Disease.Gastro hep advances · 2026Article
- An updated overview of alkaloids for the prevention and treatment of metabolic dysfunction-associated steatotic liver disease.Frontiers in pharmacology · 2026Review
- Overlapping Yet Distinct Functions of Vacuole Membrane Protein 1 and Transmembrane Protein 41B in Modulating Hepatic Lipoprotein Secretion and Autophagy.Cellular and molecular gastroenterology and hepatology · 2026Article
- Review
- Human genetics of steatotic liver disease: insights into insulin resistance and lipid metabolism.Nature metabolism · 2025Review
- Inborn errors of canonical autophagy in neurodegenerative diseases.Human molecular genetics · 2025Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 11 institutions in 4 countries.
Funding
Abstract
BACKGROUND &
aimsNon-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci that contribute to severe NAFLD by examining rare variants.
methodsWe performed whole-exome sequencing in individuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n = 301) and examined the enrichment of likely pathogenic rare variants vs. the general population. This was followed by validation at the gene level.
resultsIn patients with severe NAFLD, we observed an enrichment of the p.P426L variant (rs143545741 C>T; odds ratio [OR] 5.26, 95% CI 2.1-12.6; p = 0.003) of autophagy-related 7 (ATG7), which we characterized as a loss-of-function, vs. the general population, and an enrichment in rare variants affecting the catalytic domain (OR 13.9; 95% CI 1.9-612; p = 0.002). In the UK Biobank cohort, loss-of-function ATG7 variants increased the risk of cirrhosis and hepatocellular carcinoma (OR 3.30; 95% CI 1.1-7.5 and OR 12.30, 95% CI 2.6-36, respectively; p <0.001 for both). The low-frequency loss-of-function p.V471A variant (rs36117895 T>C) was also associated with severe NAFLD in the clinical cohort (OR 1.7; 95% CI 1.2-2.5; p = 0.003), predisposed to hepatocellular ballooning (p = 0.007) evolving to fibrosis in the Liver biopsy cohort (n = 2,268), and was associated with liver injury in the UK Biobank (aspartate aminotransferase levels, p <0.001), with a larger effect in severely obese individuals in whom it was linked to hepatocellular carcinoma (p = 0.009). ATG7 protein localized to periportal hepatocytes, particularly in the presence of ballooning. In the Liver Transcriptomic cohort (n = 125), ATG7 expression correlated with suppression of the TNFα pathway, which was conversely upregulated in p.V471A carriers.
conclusionsWe identified rare and low-frequency ATG7 loss-of-function variants that promote NAFLD progression by impairing autophagy and facilitating ballooning and inflammation. LAY SUMMARY: We found that rare mutations in a gene called autophagy-related 7 (ATG7) increase the risk of developing severe liver disease in individuals with dysmetabolism. These mutations cause an alteration in protein function and impairment of self-renewal of cellular content, leading to liver damage and inflammation.
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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.