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Most of the knowledge is centered on more homogeneous populations and studies involving an admixed group of people should be encouraged due to the great importance of understanding the human color variation. This work evaluates the <jats:italic>MC1R<\/jats:italic> diversity and the possible impacts of <jats:italic>MC1R<\/jats:italic> variants in an admixed sample population of Rio de Janeiro, Brazil, which is a product of Native American, African, and European miscegenation. Sequencing of complete coding region and part of the 3\u00b4UTR of <jats:italic>MC1R<\/jats:italic> gene identified 31 variants including one insertion and three novel synonymous substitutions in sample population grouped according to skin, hair and eye pigmentation levels. In nonmetric multidimensional scaling analysis (NMDS), three main clusters were identified, in which the Brazilian dark skin group remained in the African cluster whereas the intermediate and the light skin color phenotype in the European one. None gathered with Asians since their immigration to Brazil was a recent event. <jats:italic>In silico<\/jats:italic> analyses demonstrated that Cys35Tyr, Ile155Thr and Pro256Ser, found in our population, have a negative effect on receptor function probably due to changes on the receptor structure. Notably, Cys35Tyr mutation could potentially impair agonist binding. Altogether, this work contributes to the understanding of the genetic background of color variation on an admixed population and gives insights into the damaging effects of MC1R variants.<\/jats:p>","DOI":"10.1371\/journal.pone.0267286","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T17:24:50Z","timestamp":1650648290000},"page":"e0267286","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic diversity of the melanocortin-1 receptor in an admixed population of Rio de Janeiro: Structural and functional impacts of Cys35Tyr variant"],"prefix":"10.1371","volume":"17","author":[{"given":"Vanessa","family":"Neitzke-Montinelli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscila","family":"da Silva Figueiredo Celestino Gomes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro G.","family":"Pascutti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo S.","family":"Moura-Neto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2998-6999","authenticated-orcid":true,"given":"Rosane","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,4,22]]},"reference":[{"key":"pone.0267286.ref001","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1134\/S0006297913110035","article-title":"Malignant melanoma and melanocortin 1 receptor","volume":"78","author":"AA Rosenkranz","year":"2013","journal-title":"Biochem Biokhimiia"},{"key":"pone.0267286.ref002","doi-asserted-by":"crossref","first-page":"3544","DOI":"10.1093\/emboj\/16.12.3544","article-title":"Modulation of murine melanocyte function in vitro by agouti signal protein","volume":"16","author":"C Sakai","year":"1997","journal-title":"Embo J"},{"key":"pone.0267286.ref003","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1111\/1523-1747.ep12292572","article-title":"Agouti Signaling Protein Inhibits Melanogenesis and the Response of Human Melanocytes to \u03b1-Melanotropin","volume":"108","author":"I Suzuki","year":"1997","journal-title":"J Invest Dermatol"},{"key":"pone.0267286.ref004","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1006\/jhev.2000.0403","article-title":"The evolution of human skin coloration","volume":"39","author":"NG Jablonski","year":"2000","journal-title":"J Hum Evol"},{"key":"pone.0267286.ref005","first-page":"95","article-title":"Melanocortin 1 Receptor: Structure, Function, and Regulation","volume":"7","author":"EMW Horrell","year":"2016","journal-title":"Frontiers Genetics"},{"key":"pone.0267286.ref006","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.2147\/CMAR.S155283","article-title":"MC1R variants as melanoma risk factors independent of at-risk phenotypic characteristics: a pooled analysis from the M-SKIP project","volume":"10","author":"E Tagliabue","year":"2018","journal-title":"Cancer Management Res"},{"key":"pone.0267286.ref007","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1002\/ana.21535","article-title":"Genetic determinants of hair color and Parkinson\u2019s disease risk","volume":"65","author":"X Gao","year":"2009","journal-title":"Ann Neurol"},{"key":"pone.0267286.ref008","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1007\/s12031-014-0425-1","article-title":"The Melanocortin 1 Receptor (Mc1r) Variants Do Not Account for the Co-occurrence of Parkinson\u2019s Disease and Malignant Melanoma","volume":"54","author":"S Elincx-Benizri","year":"2014","journal-title":"J Mol Neurosci"},{"key":"pone.0267286.ref009","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1086\/302863","article-title":"Evidence for Variable Selective Pressures at MC1R","volume":"66","author":"RM Harding","year":"2000","journal-title":"Am J Hum Genetics"},{"key":"pone.0267286.ref010","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/ajpa.10263","article-title":"Geographic distribution of environmental factors influencing human skin coloration","volume":"125","author":"G. 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