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This locus contains a cluster of several genes that includes muscle rat sarcoma virus (<jats:italic>MRAS<\/jats:italic>). Common<jats:italic>MRAS<\/jats:italic>variants are also associated with CAD causing risk factors such as hypertension, dyslipidemia, obesity, and type II diabetes. The<jats:italic>MRAS<\/jats:italic>gene is an oncogene that encodes a membrane\u2010bound small GTPase. It is involved in a variety of signaling pathways, regulating cell differentiation and cell survival (mitogen\u2010activated protein kinase [MAPK]\/extracellular signal\u2010regulated kinase and phosphatidylinositol 3\u2010kinase) as well as acute phase response signaling (tumor necrosis factor [TNF] and interleukin 6 [IL6] signaling). In this review, we will summarize the role of genetic<jats:italic>MRAS<\/jats:italic>variants in the etiology of CAD and its comorbidities with the focus on tissue distribution of<jats:italic>MRAS<\/jats:italic>isoforms, cell type\/tissue specificity, and mode of action of single nucleotide variants in<jats:italic>MRAS<\/jats:italic>associated complex traits. Finally, we postulate that CAD risk variants in the<jats:italic>MRAS<\/jats:italic>locus are specific to smooth muscle cells and lead to higher levels of<jats:italic>MRAS<\/jats:italic>, particularly in arterial and cardiac tissue, resulting in MAPK\u2010dependent tissue hypertrophy or hyperplasia.<\/jats:p>","DOI":"10.1002\/iub.2805","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T11:18:51Z","timestamp":1705922331000},"page":"300-312","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>MRAS<\/scp>in coronary artery disease\u2014Unchartered territory"],"prefix":"10.1002","volume":"76","author":[{"given":"Pashmina Wiqar","family":"Shah","sequence":"first","affiliation":[{"name":"Institute for Cardiogenetics University of L\u00fcbeck L\u00fcbeck Germany"},{"name":"DZHK (German Research Centre for Cardiovascular Research) L\u00fcbeck Germany"},{"name":"University Heart Center 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