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Adv."],"published-print":{"date-parts":[[2026,7,31]]},"abstract":"<jats:p>\n                    Rhodopsin (\n                    <jats:italic toggle=\"yes\">RHO<\/jats:italic>\n                    ) missense variants are a leading cause of autosomal dominant retinitis pigmentosa (adRP), a progressive retinal degeneration. Interpreting\n                    <jats:italic toggle=\"yes\">RHO<\/jats:italic>\n                    variant pathogenicity is challenging, and understanding their disease mechanisms is essential for developing therapeutics. We present a high-resolution map of\n                    <jats:italic toggle=\"yes\">RHO<\/jats:italic>\n                    missense variant trafficking using deep mutational scanning approaches, including a surface abundance immunoassay and a complementary membrane proximity assay. This comprehensive, reproducible dataset encompassed all 6612 possible missense variants. Over 700 variants had pathogenic trafficking scores, substantially expanding the number of\n                    <jats:italic toggle=\"yes\">RHO<\/jats:italic>\n                    variants with functional data. Trafficking scores correlated with the magnitude of ER stress markers and ClinVar pathogenicity classifications. Data also identified structurally clustered mutational intolerance around the intradiscal beta-plug region. Treatment with the chaperone YC-001 restored surface trafficking in most mistrafficking variants. This functional map of\n                    <jats:italic toggle=\"yes\">RHO<\/jats:italic>\n                    variants provides a valuable resource for pathogenicity assessment, genotype-phenotype correlations, and the development of targeted therapeutic strategies for\n                    <jats:italic toggle=\"yes\">RHO<\/jats:italic>\n                    -adRP.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aef3518","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T17:59:11Z","timestamp":1785347951000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["A comprehensive map of missense trafficking variants in rhodopsin and their response to pharmacologic correction"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1764-2424","authenticated-orcid":true,"given":"Kannan V.","family":"Manian","sequence":"first","affiliation":[{"name":"Ocular 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