{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:12:52Z","timestamp":1790233972145,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,5,11]],"date-time":"2018-05-11T00:00:00Z","timestamp":1525996800000},"content-version":"vor","delay-in-days":71,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Investigation"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Importance<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\u2010binding cassette subfamily A member 3 (<jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>3) protein plays a vital role in surfactant homeostasis. Mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>3<\/jats:italic> gene lead to the development of interstitial lung disease. In the most severe manifestation, mutations can lead to a fatal respiratory distress syndrome in neonates. <jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>3 belongs to the same <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\u2010binding cassette transporter superfamily as the cystic fibrosis transmembrane conductance regulator (<jats:styled-content style=\"fixed-case\">CFTR<\/jats:styled-content>), the gene that causes cystic fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To classify <jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>3 mutations in a manner similar to <jats:styled-content style=\"fixed-case\">CFTR<\/jats:styled-content> mutations in order to take advantage of recent advances in therapeutics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sequence homology between the <jats:styled-content style=\"fixed-case\">CFTR<\/jats:styled-content> protein and the <jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>3 protein was established. The region of <jats:styled-content style=\"fixed-case\">CFTR<\/jats:styled-content> that is a target for the new potentiator class of drugs was of particular interest. We performed a literature search to obtain all published mutations that were thought to be disease causing. We classified these mutations using the established <jats:styled-content style=\"fixed-case\">CFTR<\/jats:styled-content> classification system. When possible, we drew on previous experimental classification of <jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>3 mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Although the proteins share the same overall structure, only a 19% identity was established between <jats:styled-content style=\"fixed-case\">CFTR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>3. The <jats:styled-content style=\"fixed-case\">CFTR<\/jats:styled-content> therapeutic target region has a 22% homology with the corresponding <jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>3 region. Totally 233 unique protein mutations were identified. All protein mutations were classified and mapped to a schematic diagram of the <jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>3 protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This new classification system for <jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>3, based on <jats:styled-content style=\"fixed-case\">CFTR<\/jats:styled-content> classification, will likely aid further research of clinical outcomes and identification of mutation\u2010tailored therapeutics, with the aim for improving clinical care for patients with <jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>3 mutations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ped4.12020","type":"journal-article","created":{"date-parts":[[2018,5,11]],"date-time":"2018-05-11T14:24:09Z","timestamp":1526048649000},"page":"17-24","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The classification of <scp>ATP<\/scp>\u2010binding cassette subfamily A member 3 mutations using the cystic fibrosis transmembrane conductance regulator classification system"],"prefix":"10.1002","volume":"2","author":[{"given":"Laura","family":"Denman","sequence":"first","affiliation":[{"name":"Pulmonary Division MassGeneral Hospital for Children Boston MA USA"},{"name":"Department of Pediatrics Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lael M.","family":"Yonker","sequence":"additional","affiliation":[{"name":"Pulmonary Division MassGeneral Hospital for Children Boston MA USA"},{"name":"Department of Pediatrics Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Bernard","family":"Kinane","sequence":"additional","affiliation":[{"name":"Pulmonary Division MassGeneral Hospital for Children Boston MA USA"},{"name":"Department of Pediatrics Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032178"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)31588-1"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20150100"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr508"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/01913120500323480"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3849"},{"key":"e_1_2_7_8_1","unstructured":"CrowdyE DR.Cystic Fibrosis Mutation Database.2011. 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