{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:22:20Z","timestamp":1792167740193,"version":"4.4.0"},"reference-count":119,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T00:00:00Z","timestamp":1687478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205174\/Z\/16\/Z"],"award-info":[{"award-number":["205174\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["GR598"],"award-info":[{"award-number":["GR598"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000310","name":"Retina UK","doi-asserted-by":"publisher","award":["205174\/Z\/16\/Z"],"award-info":[{"award-number":["205174\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/501100000310","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000310","name":"Retina UK","doi-asserted-by":"publisher","award":["GR598"],"award-info":[{"award-number":["GR598"]}],"id":[{"id":"10.13039\/501100000310","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>NR2E3 is a nuclear hormone receptor gene required for the correct development of the retinal rod photoreceptors. Expression of NR2E3 protein in rod cell precursors suppresses cone-specific gene expression and, in concert with other transcription factors including NRL, activates the expression of rod-specific genes. Pathogenic variants involving NR2E3 cause a spectrum of retinopathies, including enhanced S-cone syndrome, Goldmann\u2013Favre syndrome, retinitis pigmentosa, and clumped pigmentary retinal degeneration, with limited evidence of genotype\u2013phenotype correlations. A common feature of NR2E3-related disease is an abnormally high number of cone photoreceptors that are sensitive to short wavelength light, the S-cones. This characteristic has been supported by mouse studies, which have also revealed that loss of Nr2e3 function causes photoreceptors to develop as cells that are intermediate between rods and cones. While there is currently no available cure for NR2E3-related retinopathies, there are a number of emerging therapeutic strategies under investigation, including the use of viral gene therapy and gene editing, that have shown promise for the future treatment of patients with NR2E3 variants and other inherited retinal diseases. This review provides a detailed overview of the current understanding of the role of NR2E3 in normal development and disease, and the associated clinical phenotypes, animal models, and therapeutic studies.<\/jats:p>","DOI":"10.3390\/genes14071325","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T02:05:02Z","timestamp":1687745102000},"page":"1325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3): Role in Retinal Development and Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Maria","family":"Toms","sequence":"first","affiliation":[{"name":"Development, Ageing and Disease, UCL Institute of Ophthalmology, London EC1V 9EL, UK"},{"name":"Ocular Genomics and Therapeutics, The Francis Crick Institute, London NW1 1AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Ward","sequence":"additional","affiliation":[{"name":"Development, Ageing and Disease, UCL Institute of Ophthalmology, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-5360","authenticated-orcid":false,"given":"Mariya","family":"Moosajee","sequence":"additional","affiliation":[{"name":"Development, Ageing and Disease, UCL Institute of Ophthalmology, London EC1V 9EL, UK"},{"name":"Ocular Genomics and Therapeutics, The Francis Crick Institute, London NW1 1AT, UK"},{"name":"Department of Genetics, Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"},{"name":"Department of Ophthalmology, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1523\/JNEUROSCI.3571-04.2005","article-title":"The rod photoreceptor-specific nuclear receptor Nr2e3 represses transcription of multiple cone-specific genes","volume":"25","author":"Chen","year":"2005","journal-title":"J. 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