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GC\u2010C is predominantly expressed in the intestinal epithelium and regulates fluid and ion secretion in the gut. The receptor has a complex domain organization, and in the absence of structural information, mutational analysis provides clues to mechanisms of regulation of this protein. Here, we review the mutational landscape of this receptor that reveals regulatory features critical for its activity. We also summarize the available information on mutations in GC\u2010C that have been reported in humans and contribute to severe gastrointestinal abnormalities. Since GC\u2010C is also expressed in extra\u2010intestinal tissues, it is likely that mutations thus far reported in humans may also affect other organ systems, warranting a close observation of these patients in future.<\/jats:p>","DOI":"10.1002\/iub.2283","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T13:19:52Z","timestamp":1586956792000},"page":"1145-1159","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Mutational landscape of receptor guanylyl cyclase C: Functional analysis and disease\u2010related mutations"],"prefix":"10.1002","volume":"72","author":[{"given":"Avipsa","family":"Bose","sequence":"first","affiliation":[{"name":"Department of Molecular Reproduction Development and Genetics, Indian Institute of Science  Bengaluru 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