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Gene Review

RPE65  -  retinal pigment epithelium-specific...

Homo sapiens

Synonyms: All-trans-retinyl-palmitate hydrolase, BCO3, LCA2, RP20, Retinal pigment epithelium-specific 65 kDa protein, ...
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Disease relevance of RPE65


High impact information on RPE65


Biological context of RPE65


Anatomical context of RPE65


Associations of RPE65 with chemical compounds

  • Mutations in RPE65 cause early-onset blindness, and Rpe65-deficient mice lack 11-cis-retinal but overaccumulate alltrans-retinyl esters in the retinal pigment epithelium (RPE) [14].
  • RPE65 is proposed to be a substrate chaperone but may have an enzymatic role because it is closely related to carotenoid oxygenases [14].
  • These findings establish a catalytic role, in conjunction with lecithin:retinol acyltransferase, for RPE65 in synthesis of 11-cis-retinol, and its identity as the isomerohydrolase [14].
  • Identification of conserved histidines and glutamic acid as key residues for isomerohydrolase activity of RPE65, an enzyme of the visual cycle in the retinal pigment epithelium [15].
  • Here, we demonstrated that mutation of any one of the absolutely conserved four histidine and one glutamic acid residues to alanine in RPE65 abolished its isomerohydrolase activity [15].
  • This study demonstrates that RPE65 from the cone-dominant chicken RPE possesses significantly higher specific retinol isomerohydrolase activity, when compared with RPE65 from rod-dominant species, consistent with the faster regeneration rates of visual pigments in cone-dominant retinas [16].

Regulatory relationships of RPE65

  • RESULTS: We found that the transcriptional activity of the human RPE65 promoter was dramatically enhanced 10-13 fold in RPE cells co-transfected with DNA constructs phR65luc and phR65GV when compared to the human RPE65 promoter alone [17].

Other interactions of RPE65

  • We identified an apparently homozygous loss-of-function mutation of RPE65 (1p31) in one retinal dystrophy patient and an apparently homozygous loss-of-function mutation of MERTK (2q14.1) in a second retinal dystrophy patient [1].
  • The molecular data for CRB1 and RPE65 support previous hypotheses that LCA can represent the severe end of a spectrum of retinal dystrophies [18].
  • The relative contribution of each gene to the total number of mutations was as follows: CRX, 2.8%; GUCY2D, 6.3%; and RPE65, 6.8% [19].
  • We suggest that the unusual phenotypic variability in these two siblings with LCA is caused by the modifying effect of a heterozygous GUCY2D mutation observed against the disease background of a homozygous RPE65 mutation [20].
  • Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis [10].

Analytical, diagnostic and therapeutic context of RPE65


  1. Retinal dystrophy due to paternal isodisomy for chromosome 1 or chromosome 2, with homoallelism for mutations in RPE65 or MERTK, respectively. Thompson, D.A., McHenry, C.L., Li, Y., Richards, J.E., Othman, M.I., Schwinger, E., Vollrath, D., Jacobson, S.G., Gal, A. Am. J. Hum. Genet. (2002) [Pubmed]
  2. Mutations in RPE65 cause Leber's congenital amaurosis. Marlhens, F., Bareil, C., Griffoin, J.M., Zrenner, E., Amalric, P., Eliaou, C., Liu, S.Y., Harris, E., Redmond, T.M., Arnaud, B., Claustres, M., Hamel, C.P. Nat. Genet. (1997) [Pubmed]
  3. Early-onset severe rod-cone dystrophy in young children with RPE65 mutations. Lorenz, B., Gyürüs, P., Preising, M., Bremser, D., Gu, S., Andrassi, M., Gerth, C., Gal, A. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  4. Identification of RPE65 in transformed kidney cells. Ma, J.X., Zhang, D., Laser, M., Brownlee, N.A., Re, G.G., Hazen-Martin, D.J., Redmond, T.M., Crouch, R.K. FEBS Lett. (1999) [Pubmed]
  5. Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium. Jin, M., Li, S., Moghrabi, W.N., Sun, H., Travis, G.H. Cell (2005) [Pubmed]
  6. Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy. Gu, S.M., Thompson, D.A., Srikumari, C.R., Lorenz, B., Finckh, U., Nicoletti, A., Murthy, K.R., Rathmann, M., Kumaramanickavel, G., Denton, M.J., Gal, A. Nat. Genet. (1997) [Pubmed]
  7. Identifying photoreceptors in blind eyes caused by RPE65 mutations: Prerequisite for human gene therapy success. Jacobson, S.G., Aleman, T.S., Cideciyan, A.V., Sumaroka, A., Schwartz, S.B., Windsor, E.A., Traboulsi, E.I., Heon, E., Pittler, S.J., Milam, A.H., Maguire, A.M., Palczewski, K., Stone, E.M., Bennett, J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  8. Thirty-year follow-up of a patient with leber congenital amaurosis and novel RPE65 mutations. Al-Khayer, K., Hagstrom, S., Pauer, G., Zegarra, H., Sears, J., Traboulsi, E.I. Am. J. Ophthalmol. (2004) [Pubmed]
  9. Exclusion of LCA5 locus in a consanguineous Turkish family with macular coloboma-type LCA. Ozgül, R.K., Bozkurt, B., Kiratli, H., Oğüş, A. Eye (London, England) (2006) [Pubmed]
  10. Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis. Morimura, H., Fishman, G.A., Grover, S.A., Fulton, A.B., Berson, E.L., Dryja, T.P. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  11. RPE65 is the isomerohydrolase in the retinoid visual cycle. Moiseyev, G., Chen, Y., Takahashi, Y., Wu, B.X., Ma, J.X. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  12. Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Acland, G.M., Aguirre, G.D., Bennett, J., Aleman, T.S., Cideciyan, A.V., Bennicelli, J., Dejneka, N.S., Pearce-Kelling, S.E., Maguire, A.M., Palczewski, K., Hauswirth, W.W., Jacobson, S.G. Mol. Ther. (2005) [Pubmed]
  13. RPE65 of retinal pigment epithelium, a putative receptor molecule for plasma retinol-binding protein, is expressed in human keratinocytes. Hinterhuber, G., Cauza, K., Brugger, K., Dingelmaier-Hovorka, R., Horvat, R., Wolff, K., Foedinger, D. J. Invest. Dermatol. (2004) [Pubmed]
  14. Mutation of key residues of RPE65 abolishes its enzymatic role as isomerohydrolase in the visual cycle. Redmond, T.M., Poliakov, E., Yu, S., Tsai, J.Y., Lu, Z., Gentleman, S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  15. Identification of conserved histidines and glutamic acid as key residues for isomerohydrolase activity of RPE65, an enzyme of the visual cycle in the retinal pigment epithelium. Takahashi, Y., Moiseyev, G., Chen, Y., Ma, J.X. FEBS Lett. (2005) [Pubmed]
  16. RPE65 from cone-dominant chicken is a more efficient isomerohydrolase compared with that from rod-dominant species. Moiseyev, G., Takahashi, Y., Chen, Y., Kim, S., Ma, J.X. J. Biol. Chem. (2008) [Pubmed]
  17. Concurrent enhancement of transcriptional activity and specificity of a retinal pigment epithelial cell-preferential promoter. Zhang, D., Sutanto, E.N., Rakoczy, P.E. Mol. Vis. (2004) [Pubmed]
  18. Molecular genetics of Leber congenital amaurosis. Cremers, F.P., van den Hurk, J.A., den Hollander, A.I. Hum. Mol. Genet. (2002) [Pubmed]
  19. Mutation analysis of 3 genes in patients with Leber congenital amaurosis. Lotery, A.J., Namperumalsamy, P., Jacobson, S.G., Weleber, R.G., Fishman, G.A., Musarella, M.A., Hoyt, C.S., Héon, E., Levin, A., Jan, J., Lam, B., Carr, R.E., Franklin, A., Radha, S., Andorf, J.L., Sheffield, V.C., Stone, E.M. Arch. Ophthalmol. (2000) [Pubmed]
  20. A missense mutation in GUCY2D acts as a genetic modifier in RPE65-related Leber Congenital Amaurosis. Silva, E., Dharmaraj, S., Li, Y.Y., Pina, A.L., Carter, R.C., Loyer, M., Traboulsi, E., Theodossiadis, G., Koenekoop, R., Sundin, O., Maumenee, I. Ophthalmic Genet. (2004) [Pubmed]
  21. Promoter analysis of RPE65, the gene encoding a 61-kDa retinal pigment epithelium-specific protein. Nicoletti, A., Kawase, K., Thompson, D.A. Invest. Ophthalmol. Vis. Sci. (1998) [Pubmed]
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