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Here, using large\u2010scale whole\u2010exome sequencing data from 356,982 UK Biobank participants, exome\u2010wide gene\u2010based tests of rare coding variants and single\u2010variant analyses of common coding variants are performed. A total of 22 significant rare\u2010variant gene\u2010based associations involving 16 genes are identified, including 12 novel genes, 10 of which are independently supported in the All of Us cohort (N = 245,388). Single\u2010variant analyses identify 243 independent common coding variants in 126 genes, including 24 novel genes.\n                    <jats:italic>CFI<\/jats:italic>\n                    ,\n                    <jats:italic>C3<\/jats:italic>\n                    , and\n                    <jats:italic>RIOX1<\/jats:italic>\n                    show associations across retinal structure, visual function, and disease phenotypes, supporting cross\u2010domain pleiotropy. Among the disease\u2010associated genes, the novel gene\n                    <jats:italic>FYB2<\/jats:italic>\n                    is prioritized for experimental validation, supported by retinal pigment epithelium (RPE)\u2010related expression evidence and clinical relevance in Cox analyses.\n                    <jats:italic>FYB2<\/jats:italic>\n                    knockdown aggravates barrier dysfunction in human induced RPE (iRPE) cells, supporting a potential role in diabetic retinopathy. These findings define the protein\u2010coding architecture of retinal phenotypes, and support shared genetic links across retinal structure, visual function, and disease. The identified genes provide candidate targets for mechanistic investigation in blinding retinal disorders.\n                  <\/jats:p>","DOI":"10.1002\/advs.76582","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T12:05:11Z","timestamp":1784894711000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Large\u2010scale Whole\u2010Exome Sequencing Defines the Protein\u2010Coding Architecture of Retinal Structure, Visual Function, and Major Blinding Diseases"],"prefix":"10.1002","volume":"13","author":[{"given":"Jianqing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Clinical Research Center for Eye Diseases  Shanghai China"},{"name":"Department of Ophthalmology The First Affiliated Hospital of Soochow University  Suzhou 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