{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:56:30Z","timestamp":1790268990578,"version":"4.1.0"},"reference-count":73,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T00:00:00Z","timestamp":1681430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dean of the College of Health Sciences (K.S.M)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The retina-specific ATP-binding cassette transporter protein ABCA4 is responsible for properly continuing the visual cycle by removing toxic retinoid byproducts of phototransduction. Functional impairment caused by ABCA4 sequence variations is the leading cause of autosomal recessive inherited retinal disorders, including Stargardt disease, retinitis pigmentosa, and cone-rod dystrophy. To date, more than 3000 ABCA4 genetic variants have been identified, approximately 40 percent of which have not been able to be classified for pathogenicity assessments. This study examined 30 missense ABCA4 variants using AlphaFold2 protein modeling and computational structure analysis for pathogenicity prediction. All variants classified as pathogenic (n = 10) were found to have deleterious structural consequences. Eight of the ten benign variants were structurally neutral, while the remaining two resulted in mild structural changes. This study\u2019s results provided multiple lines of computational pathogenicity evidence for eight ABCA4 variants of uncertain clinical significance. Overall, in silico analyses of ABCA4 can provide a valuable tool for understanding the molecular mechanisms of retinal degeneration and their pathogenic impact.<\/jats:p>","DOI":"10.3390\/ijms24087280","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T09:23:43Z","timestamp":1681464223000},"page":"7280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Structural and Pathogenic Impacts of ABCA4 Variants in Retinal Degenerations\u2014An In-Silico Study"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7689-1677","authenticated-orcid":false,"given":"Senem","family":"Cevik","sequence":"first","affiliation":[{"name":"Department of Medical and Molecular Sciences, College of Health Sciences, University of Delaware, 16 West Main Street, Suite 302 WHL, Newark, DE 19716, USA"},{"name":"Ammon Pinizzotto Biopharmaceutical Innovation Center, 590 Avenue 1743, Newark, DE 19713, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhasis B.","family":"Biswas","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Sciences, College of Health Sciences, University of Delaware, 16 West Main Street, Suite 302 WHL, Newark, DE 19716, USA"},{"name":"Ammon Pinizzotto Biopharmaceutical Innovation Center, 590 Avenue 1743, Newark, DE 19713, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther E.","family":"Biswas-Fiss","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Sciences, College of Health Sciences, University of Delaware, 16 West Main Street, Suite 302 WHL, Newark, DE 19716, USA"},{"name":"Ammon Pinizzotto Biopharmaceutical Innovation Center, 590 Avenue 1743, Newark, DE 19713, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1023\/A:1012883306823","article-title":"Mechanistic studies of ABCR, the ABC transporter in photoreceptor outer segments responsible for autosomal recessive Stargardt disease","volume":"33","author":"Sun","year":"2001","journal-title":"J. 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