{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T22:43:29Z","timestamp":1784241809125,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,7,30]],"date-time":"2016-07-30T00:00:00Z","timestamp":1469836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["HI865\/2-1; BI893\/2-2"],"award-info":[{"award-number":["HI865\/2-1; BI893\/2-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"BMBF","award":["01GS0820"],"award-info":[{"award-number":["01GS0820"]}]},{"name":"Else Kr\u00f6ner Stiftung","award":["EKFS 2014_A114; ELAN program of the University Hos"],"award-info":[{"award-number":["EKFS 2014_A114; ELAN program of the University Hos"]}]},{"name":"Ruhr University Bochum","award":["FoRUM program"],"award-info":[{"award-number":["FoRUM program"]}]},{"name":"University Hospital Essen","award":["IFORES"],"award-info":[{"award-number":["IFORES"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The melanocortin receptor accessory protein 2 (MRAP2) is relevant for weight regulation in mice and humans. This function is likely mediated by regulation of the melanocortin\u20104 receptor (MC4R). Functional implications of human <jats:italic>MRAP2<\/jats:italic> mutations have not been described yet.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A mutation screen was conducted in <jats:italic>MRAP2<\/jats:italic> in 184 children and adolescents with (extreme) obesity and in 184 lean controls. Detected nonsynonymous variants were genotyped in larger independent study groups (300 people with obesity and 436 individuals with normal weight). The influence of mutant MRAP2 on MC4R signaling was analyzed <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>(1) Three (two novel) nonsynonymous <jats:italic>MRAP2<\/jats:italic> variants were detected: p.Ala137Thr, p.Gln174Arg, p.Arg125His (rs115655382), two synonymous variants, and three intronic variants. (2) The impact of MRAP2 on MC4R function was dependent on the ratio between the two co\u2010expressed proteins. Increased MC4R signaling was detected at MRAP2\/MC4R ratios of 2\u2009+\u20091 and above. (3) The function of MC4R was reduced with the infrequent allele at the MRAP2 p.Gln174Arg variant. (4) The three nonsynonymous mutations were each only detected once among the 484 people with obesity and not among 620 individuals with normal weight.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This was the first study describing an effect of a <jats:italic>MRAP2<\/jats:italic> mutation on MC4R function.<\/jats:p><\/jats:sec>","DOI":"10.1002\/oby.21576","type":"journal-article","created":{"date-parts":[[2016,8,29]],"date-time":"2016-08-29T05:16:10Z","timestamp":1472447770000},"page":"1976-1982","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Decreased melanocortin\u20104 receptor function conferred by an infrequent variant at the human melanocortin receptor accessory protein 2 gene"],"prefix":"10.1002","volume":"24","author":[{"given":"Laura","family":"Schonnop","sequence":"first","affiliation":[{"name":"Department of Child and Adolescent Psychiatry University Hospital Essen, University of Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Kleinau","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pediatric Endocrinology Charit\u00e9, Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolas","family":"Herrfurth","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry University Hospital Essen, University of Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u2010Lena","family":"Volckmar","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry University Hospital Essen, University of Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cigdem","family":"Cetindag","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pediatric Endocrinology Charit\u00e9, Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pediatric Endocrinology Charit\u00e9, Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Triinu","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry University Hospital Essen, University of Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Herpertz","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine and Psychotherapy LWL University Hospital, Ruhr\u2010University Bochum Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Antel","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry University Hospital Essen, University of 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