Reviewed August 2010
What is the official name of the RPE65 gene?
The official name of this gene is “retinal pigment epithelium-specific protein 65kDa.”
RPE65 is the gene's official symbol. The RPE65 gene is also known by other names, listed below.
What is the normal function of the RPE65 gene?
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 that lines the back of the eye.
The RPE65 protein is involved in a multi-step process called the visual cycle, which converts light entering the eye into electrical signals that are transmitted to the brain. When light hits photosensitive pigments in the retina, it changes a molecule called 11-cis retinal (a form of vitamin A) to another molecule called all-trans retinal. This conversion triggers a series of chemical reactions that create electrical signals. The RPE65 protein then helps convert all-trans retinal back to 11-cis retinal so the visual cycle can begin again.
How are changes in the RPE65 gene related to health conditions?
- Leber congenital amaurosis - caused by mutations in the RPE65 gene
More than 30 mutations in the RPE65 gene have been found to cause Leber congenital amaurosis. Mutations in this gene account for 6 to 16 percent of all cases of this condition.
RPE65 gene mutations lead to a partial or total loss of RPE65 protein function. As a result, all-trans retinal cannot be converted back to 11-cis retinal, and excess 11-cis retinal builds up in the retinal pigment epithelium. These abnormalities block the visual cycle, which leads to severe visual impairment beginning very early in life.
- other disorders - caused by mutations in the RPE65 gene
More than 20 mutations in the RPE65 gene have been identified in people with another eye disorder called retinitis pigmentosa. This condition is characterized by progressive vision loss caused by the gradual degeneration of light-sensing cells in the retina. The first sign of retinitis pigmentosa is usually a loss of night vision, which often becomes apparent in childhood. Over a period of years, the disease progresses to disrupt side (peripheral) vision and central vision. It may eventually lead to blindness.
The RPE65 gene mutations that cause retinitis pigmentosa disrupt RPE65 protein function, which leads to vision loss by impairing the visual cycle. Mutations in this gene appear to be an uncommon cause of retinitis pigmentosa; these genetic changes are responsible for only a small percentage of all cases.
Where is the RPE65 gene located?
Cytogenetic Location: 1p31
Molecular Location on chromosome 1: base pairs 68,428,824 to 68,449,959
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/6121))
The RPE65 gene is located on the short (p) arm of chromosome 1 at position 31.
More precisely, the RPE65 gene is located from base pair 68,428,824 to base pair 68,449,959 on chromosome 1.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about RPE65?
You and your healthcare professional may find the following resources about RPE65 helpful.
Educational resources - Information pages
- National Eye Institute: Diagram of the Eye (https://nei.nih.gov/health/eyediagram/)
- Neuroscience (second edition, 2001): The Retina (http://www.ncbi.nlm.nih.gov/books/NBK10885/)
Gene Reviews - Clinical summary
- Gene Review: Leber Congenital Amaurosis (http://www.ncbi.nlm.nih.gov/books/NBK1298)
- Gene Review: Retinitis Pigmentosa Overview (http://www.ncbi.nlm.nih.gov/books/NBK1417)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for RPE65 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=6121%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28RPE65%5BTIAB%5D%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/180069)
Research Resources - Tools for researchers
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=10294)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/6121)
- Retina International: RPE65 Mutation Database (http://www.retina-international.org/files/sci-news/rpe65mut.htm)
What other names do people use for the RPE65 gene or gene products?
- all-trans-retinyl-palmitate hydrolase
- RBP-binding membrane protein
- retinal pigment epithelium-specific 65 kDa protein
- retinitis pigmentosa 20 (autosomal recessive)
- retinoid isomerohydrolase
- retinol isomerase
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding RPE65?
autosomal recessive ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Cai X, Conley SM, Naash MI. RPE65: role in the visual cycle, human retinal disease, and gene therapy. Ophthalmic Genet. 2009 Jun;30(2):57-62. doi: 10.1080/13816810802626399. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19373675?dopt=Abstract)
- Cideciyan AV, Aleman TS, Boye SL, Schwartz SB, Kaushal S, Roman AJ, Pang JJ, Sumaroka A, Windsor EA, Wilson JM, Flotte TR, Fishman GA, Heon E, Stone EM, Byrne BJ, Jacobson SG, Hauswirth WW. Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15112-7. doi: 10.1073/pnas.0807027105. Epub 2008 Sep 22. (http://www.ncbi.nlm.nih.gov/pubmed/18809924?dopt=Abstract)
- 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18632300?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/9501220?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/6121)
- 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. Epub 2005 Sep 6. (http://www.ncbi.nlm.nih.gov/pubmed/16150724?dopt=Abstract)
- 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18762184?dopt=Abstract)
- Thompson DA, Gyürüs 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. (http://www.ncbi.nlm.nih.gov/pubmed/11095629?dopt=Abstract)
- Travis GH, Golczak M, Moise AR, Palczewski K. Diseases caused by defects in the visual cycle: retinoids as potential therapeutic agents. Annu Rev Pharmacol Toxicol. 2007;47:469-512. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16968212?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.