{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T03:14:30Z","timestamp":1783394070809,"version":"3.54.6"},"reference-count":13,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/purpose: A comprehensive review of the degree of disorder in all genes in the Retinal Information Network (RetNet) Database is implicated in inherited retinal diseases (IRDs). Their association with a missense variation was evaluated. Methods: IRD genes from RetNet were included in this study. Publicly available data on the genome aggregation database (gnomAD) were used to analyze the number of total and pathogenic missense variants. Metapredict, an accurate and high-performance predictor that reproduces consensus disorder scores, was used to calculate disorder. Main outcome measures: The main outcome measures were percent disorder, percent pathogenicity, number of total missense variants, and percent total missense variation. Results: We included 287 RetNet genes with relevant data available from gnomAD. Mean percent disorder was 26.3% \u00b1 26.0%, mean percent pathogenicity was 5.2% \u00b1 11.0%, mean number of total missense variants was 424.4 \u00b1 450.0, and mean percent total missense was 50.0% \u00b1 13.4%. The percent disorder followed a bimodal distribution with the highest number of occurrences in the 0 to 10th disorder decile. The five outlier proteins in the first disorder decile with a higher-than-expected number of total missense variation were identified (HMCN1, ADGRV, USH2A, DYNC2H1, LAMA1, and SLC38A8). When excluded, % total missense was significantly associated with percent disorder (R = 0.238 and p = 0.0240). Conclusions: This novel study examining all genes implicated in IRDs found that the majority genes had a disorder in the 0 to 10th decile and were relatively intolerant to missense variation. This may have future utility when interpreting variants of undetermined significance and missense variants.<\/jats:p>","DOI":"10.3390\/genes14081601","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T12:35:42Z","timestamp":1691498142000},"page":"1601","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Comprehensive Report of Intrinsically Disordered Regions in Inherited Retinal Diseases"],"prefix":"10.3390","volume":"14","author":[{"given":"Karen E.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pediatric Ophthalmology and Strabismus, Wills Eye Hospital, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose S.","family":"Pulido","sequence":"additional","affiliation":[{"name":"Retina Service, Wills Eye Hospital, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5770-279X","authenticated-orcid":false,"given":"Mariana M.","family":"da Palma","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Federal University of S\u00e3o Paulo, UNIFESP, S\u00e3o Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Procopio","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology and Strabismus, Wills Eye Hospital, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3015-3545","authenticated-orcid":false,"given":"Robert B.","family":"Hufnagel","sequence":"additional","affiliation":[{"name":"Medical Genetics and Ophthalmic Genetics Unit, National Eye Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1111\/ceo.13917","article-title":"Inherited retinal diseases: Therapeutics, clinical trials and end points\u2014A review","volume":"49","author":"Georgiou","year":"2021","journal-title":"Clin. 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(2021). metapredict: A fast, accurate, and easy-to-use predictor of consensus disorder and structure. bioRxiv.","DOI":"10.1101\/2021.05.30.446349"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/8\/1601\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:27:51Z","timestamp":1760128071000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/8\/1601"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,8]]},"references-count":13,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["genes14081601"],"URL":"https:\/\/doi.org\/10.3390\/genes14081601","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,8]]}}}