{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:09:08Z","timestamp":1789520948097,"version":"build-2803163510"},"reference-count":81,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2018,5,25]],"date-time":"2018-05-25T00:00:00Z","timestamp":1527206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University Parthenope","award":["Finanziamento per il Sostegno alla Ricerca Individuale di Ateneo, Annualit\u00e0 2016"],"award-info":[{"award-number":["Finanziamento per il Sostegno alla Ricerca Individuale di Ateneo, Annualit\u00e0 2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aquaporins (AQPs) are among the best structural-characterized membrane proteins, fulfilling the role of allowing water flux across cellular membranes. Thus far, 34 single amino acid polymorphisms have been reported in HUMSAVAR for human aquaporins as disease-related. They affect AQP2, AQP5 and AQP8, where they are associated with nephrogenic diabetes insipidus, keratoderma and colorectal cancer, respectively. For half of these mutations, although they are mostly experimentally characterized in their dysfunctional phenotypes, a structural characterization at a molecular level is still missing. In this work, we focus on such mutations and discuss what the structural defects are that they appear to cause. To achieve this aim, we built a 3D molecular model for each mutant and explored the effect of the mutation on all of their structural features. Based on these analyses, we could collect the structural defects of all the pathogenic mutations (here or previously analysed) under few main categories, that we found to nicely correlate with the experimental phenotypes reported for several of the analysed mutants. Some of the structural analyses we present here provide a rationale for previously experimentally observed phenotypes. Furthermore, our comprehensive overview can be used as a reference frame for the interpretation, on a structural basis, of defective phenotypes of other aquaporin pathogenic mutants.<\/jats:p>","DOI":"10.3390\/ijms19061577","type":"journal-article","created":{"date-parts":[[2018,5,28]],"date-time":"2018-05-28T03:54:21Z","timestamp":1527479661000},"page":"1577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Structural Basis for Mutations of Human Aquaporins Associated to Genetic Diseases"],"prefix":"10.3390","volume":"19","author":[{"given":"Luisa","family":"Calvanese","sequence":"first","affiliation":[{"name":"CIRPeB, University of Naples Federico II, Napoli I-80134, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"D\u2019Auria","sequence":"additional","affiliation":[{"name":"CIRPeB, University of Naples Federico II, Napoli I-80134, Italy"},{"name":"Department of Pharmacy, University of Naples Federico II, Napoli I-80134, Italy"},{"name":"Institute of Biostructures and Bioimaging, CNR, Napoli I-80134, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vangone","sequence":"additional","affiliation":[{"name":"Bijvoet Center for Biomolecular Research, Faculty of Science, Department of Chemistry, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3758-2716","authenticated-orcid":false,"given":"Lucia","family":"Falcigno","sequence":"additional","affiliation":[{"name":"CIRPeB, University of Naples Federico II, Napoli I-80134, Italy"},{"name":"Department of Pharmacy, University of Naples Federico II, Napoli I-80134, Italy"},{"name":"Institute of Biostructures and Bioimaging, CNR, Napoli I-80134, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6156-6249","authenticated-orcid":false,"given":"Romina","family":"Oliva","sequence":"additional","affiliation":[{"name":"Department of Sciences and Technologies, University Parthenope of Naples, Napoli I-80143, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0959-440X(02)00355-X","article-title":"Structure and function of water channels","volume":"12","author":"Fujiyoshi","year":"2002","journal-title":"Curr. 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