{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T05:26:56Z","timestamp":1772429216561,"version":"3.50.1"},"reference-count":13,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T00:00:00Z","timestamp":1442880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["SAF2012\u201032134"],"award-info":[{"award-number":["SAF2012\u201032134"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R56AR065483"],"award-info":[{"award-number":["R56AR065483"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Melanocortin 1 receptor (<jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>1R), a Gs protein\u2010coupled receptor of the melanocyte's plasma membrane, is a major determinant of skin pigmentation and phototype. Upon activation by <jats:italic>\u03b1<\/jats:italic>\u2010melanocyte stimulating hormone, <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>1R triggers the <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> cascade to stimulate eumelanogenesis. We used whole\u2010exome sequencing to identify causative alleles in Pakistani families with skin and hair hypopigmentation. Six <jats:italic><jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>1R<\/jats:italic> mutations segregated with the phenotype in seven families, including a p.Val174del in\u2010frame deletion and a p.Tyr298* nonsense mutation, that were analyzed for function in heterologous <jats:styled-content style=\"fixed-case\">HEK<\/jats:styled-content>293 cells. p.Tyr298* <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>1R showed no agonist\u2010induced signaling to the <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> pathways, nor detectable agonist binding. Conversely, signaling was comparable for p.Val174del and wild\u2010type in <jats:styled-content style=\"fixed-case\">HEK<\/jats:styled-content> cells overexpressing the proteins, but binding analysis suggested impaired cell surface expression. Flow cytometry and confocal imaging studies revealed reduced plasma membrane expression of p.Val174del and p.Tyr298*. Therefore, p.Tyr298* was a total loss\u2010of\u2010function (<jats:styled-content style=\"fixed-case\">LOF<\/jats:styled-content>) allele, while p.Val174del displayed a partial <jats:styled-content style=\"fixed-case\">LOF<\/jats:styled-content> attribute.<\/jats:p>","DOI":"10.1111\/pcmr.12400","type":"journal-article","created":{"date-parts":[[2015,7,21]],"date-time":"2015-07-21T15:07:48Z","timestamp":1437491268000},"page":"730-735","source":"Crossref","is-referenced-by-count":6,"title":["Identification and functional characterization of natural human melanocortin 1 receptor mutant alleles in Pakistani population"],"prefix":"10.1111","volume":"28","author":[{"given":"Mohsin","family":"Shahzad","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery School of Medicine University of Maryland Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Sires Campos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Medicine University of Murcia and IMIB\u2010Arrixaca Murcia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nabeela","family":"Tariq","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology &amp; Biotechnology Bahauddin Zakariya University Multan Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Herraiz Serrano","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Medicine University of Murcia and IMIB\u2010Arrixaca Murcia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rizwan","family":"Yousaf","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery School of Medicine University of Maryland Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celia","family":"Jim\u00e9nez\u2010Cervantes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Medicine University of Murcia and IMIB\u2010Arrixaca Murcia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sairah","family":"Yousaf","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery School of Medicine University of Maryland Baltimore MD USA"},{"name":"Institute of Molecular Biology &amp; Biotechnology Bahauddin Zakariya University Multan Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yar M.","family":"Waryah","sequence":"additional","affiliation":[{"name":"Molecular Biology &amp; Genetics Department Medical Research Center Liaquat University of Medical &amp; Health Sciences Jamshoro Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haseeb A.","family":"Dad","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences University of Veterinary &amp; Animal Sciences Lahore Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth M.","family":"Blue","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Medicine University of Washington Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nara","family":"Sobreira","sequence":"additional","affiliation":[{"name":"McKusick\u2010Nathans Institute of Genetic Medicine Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesc","family":"L\u00f3pez\u2010Gir\u00e1ldez","sequence":"additional","affiliation":[{"name":"Yale Center for Genome Analysis Yale University West Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"University of Washington Center for Mendelian Genomics","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tasleem","family":"Kausar","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology &amp; Biotechnology Bahauddin Zakariya University Multan Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Ali","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology &amp; Biotechnology Bahauddin Zakariya University Multan Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali M.","family":"Waryah","sequence":"additional","affiliation":[{"name":"Molecular Biology &amp; Genetics Department Medical Research Center Liaquat University of Medical &amp; Health Sciences Jamshoro Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saima","family":"Riazuddin","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery School of Medicine University of Maryland Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rehan S.","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology &amp; Biotechnology Bahauddin Zakariya University Multan Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 C.","family":"Garc\u00eda\u2010Borr\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Medicine University of Murcia and IMIB\u2010Arrixaca Murcia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zubair M.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery School of Medicine University of Maryland Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,9,22]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.2003.00067.x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.2011.00970.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.09.023"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0217"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1127515"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.2003.00073.x"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.12314.x"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9253"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700036"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21804"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2004.11.030"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1195-328"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R700026200"}],"container-title":["Pigment Cell &amp; Melanoma Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpcmr.12400","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcmr.12400","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T16:11:18Z","timestamp":1695571878000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pcmr.12400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,22]]},"references-count":13,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1111\/pcmr.12400"],"URL":"https:\/\/doi.org\/10.1111\/pcmr.12400","archive":["Portico"],"relation":{},"ISSN":["1755-1471","1755-148X"],"issn-type":[{"value":"1755-1471","type":"print"},{"value":"1755-148X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,22]]}}}