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Precise regulation of receptor expression provides the necessary balance to achieve healthy immune homeostasis by establishing an appropriate immune threshold to limit autoimmunity but respond effectively to infection. The underlying genetics of the\n                    <jats:italic>FCGR<\/jats:italic>\n                    gene family are central to achieving this immune threshold by regulating affinity for IgG, signaling efficacy, and receptor expression. The\n                    <jats:italic>FCGR<\/jats:italic>\n                    gene locus was duplicated during evolution, retaining very high homology and resulting in a genomic region that is technically difficult to study. Here, we review the recent evolution of the gene family in mammals, its complexity and variation through copy number variation and single\u2010nucleotide polymorphism, and impact of these on disease incidence, resolution, and therapeutic antibody efficacy. We also discuss the progress and limitations of current approaches to study the region and emphasize how new genomics technologies will likely resolve much of the current confusion in the field. This will lead to definitive conclusions on the impact of genetic variation within the\n                    <jats:italic>FCGR<\/jats:italic>\n                    gene locus on immune function and disease.\n                  <\/jats:p>","DOI":"10.1111\/imr.13401","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T08:19:04Z","timestamp":1727684344000},"page":"65-97","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Fc gamma receptors: Their evolution, genomic architecture, genetic variation, and impact on human disease"],"prefix":"10.1111","volume":"328","author":[{"given":"Sarah","family":"Frampton","sequence":"first","affiliation":[{"name":"Cancer Genomics Group, Faculty of Medicine, School of Cancer Sciences University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Smith","sequence":"additional","affiliation":[{"name":"Antibody and Vaccine Group, Faculty of Medicine, School of Cancer Sciences, Centre for Cancer Immunology University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Ferson","sequence":"additional","affiliation":[{"name":"Cancer Genomics Group, Faculty of Medicine, School of Cancer Sciences University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Gibson","sequence":"additional","affiliation":[{"name":"Cancer Genomics Group, Faculty of Medicine, School of Cancer Sciences University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Hollox","sequence":"additional","affiliation":[{"name":"Department of Genetics, Genomics and Cancer Sciences College of Life Sciences, University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2077-089X","authenticated-orcid":false,"given":"Mark S.","family":"Cragg","sequence":"additional","affiliation":[{"name":"Antibody and Vaccine Group, Faculty of Medicine, School of Cancer Sciences, Centre for Cancer Immunology University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan C.","family":"Strefford","sequence":"additional","affiliation":[{"name":"Cancer Genomics Group, Faculty of Medicine, School of Cancer Sciences University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,30]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00079"},{"key":"e_1_2_17_3_1","first-page":"105","volume-title":"Fc\u03b3Rs in Health and 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