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URL of this page: https://medlineplus.gov/genetics/gene/rpe65/

RPE65 gene

retinoid isomerohydrolase RPE65

Normal Function

The RPE65 gene provides instructions for making a protein that is essential for normal vision. The RPE65 protein is produced in a thin layer of cells at the back of the eye called the retinal pigment epithelium (RPE). This cell layer supports and nourishes the retina, which is the light-sensitive tissue at the back of the eye that detects light and color. 

The RPE65 protein is a key enzyme in a multistep process called the visual cycle (also called the retinoid or vitamin A cycle), which recycles certain molecules in the retina after they are exposed to light. When light meets the retina, it changes a molecule called 11-cis retinal (a form of vitamin A) into another form of vitamin A called all-trans retinal. This conversion triggers a series of chemical reactions that create electrical signals. Later in the visual cycle, the RPE65 protein converts a molecule called all-trans retinyl ester into a molecule called 11-cis retinol. Other enzymes then produce 11-cis retinal from 11-cis retinol so that the visual cycle can begin again. 

Health Conditions Related to Genetic Changes

Leber congenital amaurosis

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the RPE65 gene have been found to cause Leber congenital amaurosis type 2. Leber congenital amaurosis is a group of eye disorders that affect the retina. People with Leber congenital amaurosis typically have vision loss that begins during the first year of life. Pathogenic variants in the RPE65 gene account for up to 10 percent of all cases of Leber congenital amaurosis.

The RPE65 gene variants that cause Leber congenital amaurosis type 2 lead to a partial or total loss of RPE65 protein function. As a result, the conversion of all-trans retinal back to 11-cis retinal is impaired, which disrupts photoreceptor function and causes a buildup of molecules in the RPE. This leads to the retinal degeneration and the severe visual impairment that is characteristic of Leber congenital amaurosis type 2.

More About This Health Condition

Fundus albipunctatus

MedlinePlus Genetics provides information about Fundus albipunctatus

More About This Health Condition

Retinitis pigmentosa

MedlinePlus Genetics provides information about Retinitis pigmentosa

More About This Health Condition

Other Names for This Gene

  • all-trans-retinyl-palmitate hydrolase
  • BCO family, member 3
  • BCO3
  • LCA2
  • rd12
  • retinol isomerase

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Daich Varela M, Cabral de Guimaraes TA, Georgiou M, Michaelides M. Leber congenital amaurosis/early-onset severe retinal dystrophy: current management and clinical trials. Br J Ophthalmol. 2022 Apr;106(4):445-451. doi: 10.1136/bjophthalmol-2020-318483. Epub 2021 Mar 12. Citation on PubMed
  • den Hollander AI, Roepman R, Koenekoop RK, Cremers FP. Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog Retin Eye Res. 2008 Jul;27(4):391-419. doi: 10.1016/j.preteyeres.2008.05.003. Epub 2008 Jun 1. Citation on PubMed
  • Huang CH, Yang CM, Yang CH, Hou YC, Chen TC. Leber's Congenital Amaurosis: Current Concepts of Genotype-Phenotype Correlations. Genes (Basel). 2021 Aug 19;12(8):1261. doi: 10.3390/genes12081261. Citation on PubMed
  • Koritala BA, Pennesi M. Autosomal Recessive RPE65-Related Retinal Degeneration. 2019 Nov 14 [updated 2026 Jan 8]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK549574/ Citation on PubMed
  • Kumaran N, Pennesi ME, Yang P, Trzupek KM, Michaelides M. Nonsyndromic Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy Overview. 2018 Oct 4 [updated 2025 Dec 4]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK531510/ Citation on PubMed
  • Leroy BP, Fischer MD, Flannery JG, MacLaren RE, Dalkara D, Scholl HPN, Chung DC, Spera C, Viriato D, Banhazi J. Gene Therapy for Inherited Retinal Disease: Long-Term Durability of Effect. Ophthalmic Res. 2023;66(1):179-196. doi: 10.1159/000526317. Epub 2022 Sep 14. Citation on PubMed
  • Maguire AM, Russell S, Chung DC, Yu ZF, Tillman A, Drack AV, Simonelli F, Leroy BP, Reape KZ, High KA, Bennett J. Durability of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease: Phase 3 Results at 3 and 4 Years. Ophthalmology. 2021 Oct;128(10):1460-1468. doi: 10.1016/j.ophtha.2021.03.031. Epub 2021 Mar 30. Citation on PubMed
  • Morimura H, Fishman GA, Grover SA, Fulton AB, Berson EL, Dryja TP. Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3088-93. doi: 10.1073/pnas.95.6.3088. Citation on PubMed or Free article on PubMed Central
  • Pierce EA, Bennett J. The Status of RPE65 Gene Therapy Trials: Safety and Efficacy. Cold Spring Harb Perspect Med. 2015 Jan 29;5(9):a017285. doi: 10.1101/cshperspect.a017285. Citation on PubMed
  • Redmond TM, Poliakov E, Yu S, Tsai JY, Lu Z, Gentleman S. Mutation of key residues of RPE65 abolishes its enzymatic role as isomerohydrolase in the visual cycle. Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13658-63. doi: 10.1073/pnas.0504167102. Epub 2005 Sep 6. Citation on PubMed or Free article on PubMed Central
  • Redmond TM. Focus on Molecules: RPE65, the visual cycle retinol isomerase. Exp Eye Res. 2009 May;88(5):846-7. doi: 10.1016/j.exer.2008.07.015. Epub 2008 Aug 14. No abstract available. Citation on PubMed or Free article on PubMed Central
  • Sodi A, Banfi S, Testa F, Della Corte M, Passerini I, Pelo E, Rossi S, Simonelli F; Italian IRD Working Group. RPE65-associated inherited retinal diseases: consensus recommendations for eligibility to gene therapy. Orphanet J Rare Dis. 2021 Jun 4;16(1):257. doi: 10.1186/s13023-021-01868-4. Citation on PubMed
  • Thompson DA, Gyurus P, Fleischer LL, Bingham EL, McHenry CL, Apfelstedt-Sylla E, Zrenner E, Lorenz B, Richards JE, Jacobson SG, Sieving PA, Gal A. Genetics and phenotypes of RPE65 mutations in inherited retinal degeneration. Invest Ophthalmol Vis Sci. 2000 Dec;41(13):4293-9. Citation on PubMed

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