Property Summary

NCBI Gene PubMed Count 77
PubMed Score 537.21
PubTator Score 263.35

Knowledge Summary


No data available


  Differential Expression (6)

Disease log2 FC p
astrocytic glioma 2.700 5.2e-04
posterior fossa group B ependymoma 2.700 3.1e-07
glioblastoma 1.200 2.1e-02
adult high grade glioma 2.100 2.8e-05
psoriasis -1.600 7.4e-13
facioscapulohumeral dystrophy 2.400 1.0e-04

Protein-protein Interaction (3)

Gene RIF (60)

26427455 Data show that 4-phenylbutyrate (PBA) displayed a significant synergistic effect on the low temperature-mediated rescue of the mutant isomerase activity of RPE65.
26427430 Studies indicate that patients with retinol isomerase RPE65R91W mutation have useful cone-mediated vision in the first decade of life, suggesting partial activity of the mutant RPE65R91W protein.
26392743 Influx of T lymphocytes was associated with retinal pigment epithelium and choroidal thinning and diminished expression of RPE65 mRNA, an essential enzyme of the visual cycle.
26364624 Expressions of MDSC, FOXP3+TILs, and CTLA-4 are relative stable after nCRT
25972377 These data also help define minimal requirements of chromophore for photoreceptor survival in vivo and may be useful in assessing a beneficial therapeutic dose for RPE65 gene therapy in humans.
25752820 three Leber congenital amaurosis -associated RPE65 mutants (R91W, Y249C and R515W) undergo rapid proteasomal degradation mediated by the 26 S proteasome non-ATPase regulatory subunit 13.
25351180 We showed that miR-410 directly regulates predicted target genes OTX2 and RPE65.
25286304 Studies indicate that patients consistently reported improvement in their vision following delivery of recombinant adenoassociated virus (rAAV) that carried retinal pigment epithelium 65 protein (REP65) gene.
25257057 All RPE65-mutant observers have consistent and substantial losses in temporal acuity and sensitivity compared with normal observers.
25112876 when an amino-terminal fragment (Met(1)-Arg(33)) of the N170K/K297G double mutant of hRPE65 was replaced with the corresponding cRPE65 fragment, the isomerohydrolase activity was further increased to a level similar to that of cRPE65.
24849605 properties of disease causing RPE65 with regard to molecular pathogenic mechanism
24771178 We identified a novel LCA-related homozygous RPE65 mutation associated with a severe clinical presentation including an early and severe cone dysfunction.
23878505 These results strongly suggest that causal mutations in RPE65 are responsible for retinal dystrophy in the affected individuals of consanguineous Pakistani families.
23341016 the RPE65-LCA patients had higher variability in kinetic field extent. VA variability in RPE65-LCA fell within reported results for retinitis pigmentosa.
23335596 These results indicate that the non-viral delivery of hRPE65 vectors can result in persistent, therapeutically efficacious gene expression in the retinal pigment epithelium .
22509104 Compound heterozygous missense mutations in the RPE65 gene, Leu67Arg and Tyr368Cys, are related to a relatively mild Leber congenital amaurosis phenotype in Chinese patients.
22171060 These data suggest that cone RPE65 supports human diurnal vision, potentially enhancing our strategies for treating Leber congenital amaurosis Type 2.
21931134 The structural features of the retina and retinal pigment epithelium in postmortem donor eyes of a 56-year-old patient with a homozygous missense RPE65 mutation correlate the pathology with the patient's visual function.
21911650 Gene therapy for Leber congenital amaurosis caused by RPE65 mutations is sufficiently safe and substantially efficacious in the extrafoveal retina.
21736383 found that the aromatic lipophilic spin traps such as N-tert-butyl-alpha-phenylnitrone (PBN), 2,2-dimethyl-4-phenyl-2H-imidazole-1-oxide (DMPIO), and nitrosobenzene (NB) strongly inhibit RPE65 isomerohydrolase activity in vitro
21654732 Dominant mutation in RPE65 identified by whole-exome sequencing causes retinitis pigmentosa with choroidal involvement.
21211845 This is the first reported association between compound heterozygous RPE65 mutations and fundus albipunctatus, indicative of a mutation-specific phenotypic effect in this gene.
20811047 To describe in detail the features of Severe Early Childhood Onset Retinal Dystrophy (SECORD) and differentiate it from Lebers congenital amaurosis, caused by RPE65 mutation.
20801516 Observational study of genetic testing. (HuGE Navigator)
20591486 Observational study of genetic testing. (HuGE Navigator)
20510285 oxidative stress during the visual cycle results in cleavage of RPE65
20399883 Congenital loss of chromophore production due to RPE65-deficiency together with progressive photoreceptor degeneration cause severe and progressive loss of vision.
20356843 FATP1 inhibits 11-cis retinol formation via interaction with the visual cycle retinoid isomerase RPE65 and lecithin:retinol acyltransferase
20043869 Loss of charge at the E417Q position of RPE65 may represent a mechanism by which the E417Q mutation causes blindness in Leber congenital amaurosis patients.
19959640 Variations of macular microstructures were observed among LCA (Leber congenital amaurosis) patients with different genotypes.
19920137 RPE65 is not inherently 11-cis-specific and can produce both 11- and 13-cis isomers, supporting a carbocation (or radical cation) mechanism for isomerization.
19806502 Studies demonstrated improvements in rod and cone visual function in patients with RPE65-LCA administered rAAV2-CBSB-hRPE65.
19753312 Observational study of gene-disease association. (HuGE Navigator)
19431183 observed complete concordance between the predicted pathogenicities of missense variations in the RPE65 gene and retinoid isomerase activities measured in a functional assay
19117922 patients with RPE65-Leber congenital amaurosis had abnormal electroretinographys even at the youngest ages
19049981 results indicate that the newly identified Cys-112 palmitylation site is essential for the membrane association and activity of RPE65
18774912 Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial.
18766986 RPE65 replacement in two human trials with a total of six LCA (Leber congenital amaurosis) patients were documented by visual acuity measurements.
18722466 the role of this mutation in RPE65 inactivation, detailed biochemical studies of the mutant along with a structural analysis of the 244 amino acid position with respect to amino acids known to be important for RPE65-dependent retinoid isomerization.
18599565 The mild clinical phenotype observed is consistent with the residual activity of a severely hypomorphic mutant RPE65.
18539930 Differences in the topography of residual photoreceptors in children with RPE65-LCA suggest that it may be advisable to use individualized outer nuclear layer mapping to guide the location of subretinal injections for gene therapy
18484312 Mutations in the RPE65 gene are rare in patients with leber congenital amaurosis
18484312 Observational study of gene-disease association. (HuGE Navigator)
18216020 RPE65 from the cone-dominant chicken RPE possesses significantly higher specific retinol isomerohydrolase activity, when compared with RPE65 from rod-dominant species
17848510 Early cone photoreceptor losses in RPE65-LCA suggest that robust RPE65-based visual chromophore production is important for cones.
17724218 Observational study of gene-disease association. (HuGE Navigator)
17724218 RPE65 gene mutations represented a significant cause of LCA in the Italian population, whereas GUCY2D and CEP290 mutations had a lower frequency than that found in other reports.
17651254 Testing confirms the diagnosis at the molecular level and allows for a more precise prognosis of the possible future clinical evolution
17197551 The results demand critical consideration of the human disease mechanism and the therapeutic approach in patients with mutations in the putative visual cycle gene RDH12.
16754667 mutations may result in critical structural alterations of RPE65 protein, disrupt its membrane association, and consequently impair its isomerohydrolase activity, leading to retinal degeneration
16518657 We identified and characterised an endemic form of early onset rod-cone dystrophy in a consanguineous population from northeastern Tunisia, due to the prevalence of a single RPE65 mutation.
16272259 AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 mutations may have roles in juvenile retinitis pigmentosa
16198348 conserved glutamic acid and histidine residues are essential for the isomerohydrolase activity of RPE65 and its stability
15837919 Gene therapy with this protein to cure Leber congenital amaurosis; Gene therapy in Rpe65(-/-) mice at advanced-disease stages show some success
15009723 Colocalization of plasma retinol-binding protein with RPE65 and affinity binding suggest a direct interaction of RPE65 with plasma retinol-binding protein in cultured human keratinocytes that might be involved in retinoid uptake of keratinocytes.
14962443 The RPE65 mutations K303X and Y431C in compound heterozygous form cause progressive visual compromise that starts in childhood and advances to severe visual loss by the fourth decade of life.
12357075 multiplex PCR follwed by sequencing to screen for mutations in the 14 exons of the RPE65 gene in early-childhood-onset autosomal recessive retinitis pigmentosa and Leber's congenital amaurosis patients
11786058 RPE65 mutations present in compound heterozygous form cause severe visual compromise.
11727200 retinal dystrophy due to paternal isodisomy for chromosome 1 or chromosome 2, with homoallelism for mutations in RPE65 or MERTK, respectively
11462243 novel mutations in patients with Leber congenital amaurosis

AA Sequence


Text Mined References (87)

PMID Year Title
26427455 2016 Functional Rescue of Retinal Degeneration-Associated Mutant RPE65 Proteins.
26427430 2016 The Consequences of Hypomorphic RPE65 for Rod and Cone Photoreceptors.
26392743 2015 Thinning of the RPE and choroid associated with T lymphocyte recruitment in aged and light-challenged mice.
26364624 2015 Using patient-specific induced pluripotent stem cells to interrogate the pathogenicity of a novel retinal pigment epithelium-specific 65 kDa cryptic splice site mutation and confirm eligibility for enrollment into a clinical gene augmentation trial.
25972377 2015 Mouse model of human RPE65 P25L hypomorph resembles wild type under normal light rearing but is fully resistant to acute light damage.
25752820 2015 Temperature-sensitive retinoid isomerase activity of RPE65 mutants associated with Leber Congenital Amaurosis.
25351180 2015 miR-410 Inhibition Induces RPE Differentiation of Amniotic Epithelial Stem Cells via Overexpression of OTX2 and RPE65.
25286304 2014 Gene therapy for eye as regenerative medicine? Lessons from RPE65 gene therapy for Leber's Congenital Amaurosis.
25257057 2014 Nature of the visual loss in observers with Leber's congenital amaurosis caused by specific mutations in RPE65.
25112876 2014 Identification of key residues determining isomerohydrolase activity of human RPE65.
24849605 2014 Rescue of enzymatic function for disease-associated RPE65 proteins containing various missense mutations in non-active sites.
24771178 2014 Cone-rod dystrophy caused by a novel homozygous RPE65 mutation in Leber congenital amaurosis.
23878505 2013 Novel mutations in RPE65 identified in consanguineous Pakistani families with retinal dystrophy.
23341016 2013 Intervisit variability of visual parameters in Leber congenital amaurosis caused by RPE65 mutations.
23335596 2013 S/MAR-containing DNA nanoparticles promote persistent RPE gene expression and improvement in RPE65-associated LCA.
22509104 2012 Novel RPE65 mutations associated with Leber congenital amaurosis in Chinese patients.
22334370 2012 Next-generation genetic testing for retinitis pigmentosa.
22171060 2011 RPE65 is present in human green/red cones and promotes photopigment regeneration in an in vitro cone cell model.
21931134 2011 Histopathology and functional correlations in a patient with a mutation in RPE65, the gene for retinol isomerase.
21911650 2012 Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years.
21736383 2011 Aromatic lipophilic spin traps effectively inhibit RPE65 isomerohydrolase activity.
21654732 2011 A dominant mutation in RPE65 identified by whole-exome sequencing causes retinitis pigmentosa with choroidal involvement.
21602930 2011 Detection of variants in 15 genes in 87 unrelated Chinese patients with Leber congenital amaurosis.
21493626 2011 The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65.
21211845 2011 Fundus albipunctatus associated with compound heterozygous mutations in RPE65.
20811047 2011 The phenotype of Severe Early Childhood Onset Retinal Dystrophy (SECORD) from mutation of RPE65 and differentiation from Leber congenital amaurosis.
20801516 2011 Simultaneous mutation detection in 90 retinal disease genes in multiple patients using a custom-designed 300-kb retinal resequencing chip.
20591486 2010 Development of a diagnostic genetic test for simplex and autosomal recessive retinitis pigmentosa.
20510285 2010 Cleavage of the retinal pigment epithelium-specific protein RPE65 under oxidative stress.
20399883 2010 Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy.
20356843 2010 FATP1 inhibits 11-cis retinol formation via interaction with the visual cycle retinoid isomerase RPE65 and lecithin:retinol acyltransferase.
20043869 2010 Negative charge of the glutamic acid 417 residue is crucial for isomerohydrolase activity of RPE65.
19959640 2010 Differential macular morphology in patients with RPE65-, CEP290-, GUCY2D-, and AIPL1-related Leber congenital amaurosis.
19920137 2010 RPE65, visual cycle retinol isomerase, is not inherently 11-cis-specific: support for a carbocation mechanism of retinol isomerization.
19806502 2009 An analysis of retinal gene therapy clinical trials.
19753312 2009 Mutations that are a common cause of Leber congenital amaurosis in northern America are rare in southern India.
19431183 2009 Predicting the pathogenicity of RPE65 mutations.
19117922 2009 Defining the residual vision in leber congenital amaurosis caused by RPE65 mutations.
19049981 2009 Identification of a novel palmitylation site essential for membrane association and isomerohydrolase activity of RPE65.
18774912 2008 Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial.
18766986 2008 Successful RPE65 gene replacement and improved visual function in humans.
18722466 2008 Impact of retinal disease-associated RPE65 mutations on retinoid isomerization.
18682808 2008 Molecular characterization of Leber congenital amaurosis in Koreans.
18599565 2008 A comprehensive clinical and biochemical functional study of a novel RPE65 hypomorphic mutation.
18539930 2008 Photoreceptor layer topography in children with leber congenital amaurosis caused by RPE65 mutations.
18484312 2008 Screening of the RPE65 gene in the Asian Indian patients with leber congenital amaurosis.
18216020 2008 RPE65 from cone-dominant chicken is a more efficient isomerohydrolase compared with that from rod-dominant species.
17848510 2007 Human cone photoreceptor dependence on RPE65 isomerase.
17724218 2007 Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients.
17651254 2007 Genetic testing for retinal dystrophies and dysfunctions: benefits, dilemmas and solutions.
17297704 2006 Gene symbol: RPE65. Disease: Leber's congenital amaurosis. Accession #Hm0548.
17197551 2007 RDH12 and RPE65, visual cycle genes causing leber congenital amaurosis, differ in disease expression.
16754667 2006 Two point mutations of RPE65 from patients with retinal dystrophies decrease the stability of RPE65 protein and abolish its isomerohydrolase activity.
16710414 2006 The DNA sequence and biological annotation of human chromosome 1.
16518657 2006 Phenotype of three consanguineous Tunisian families with early-onset retinal degeneration caused by an R91W homozygous mutation in the RPE65 gene.
16272259 2005 Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa.
16205573 Evaluation of genotype-phenotype associations in leber congenital amaurosis.
16198348 2005 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.
16116091 2005 RPE65 is the isomerohydrolase in the retinoid visual cycle.
15837919 2005 Identifying photoreceptors in blind eyes caused by RPE65 mutations: Prerequisite for human gene therapy success.
15557452 2004 A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15024725 2004 Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis.
15009723 2004 RPE65 of retinal pigment epithelium, a putative receptor molecule for plasma retinol-binding protein, is expressed in human keratinocytes.
14962443 2004 Thirty-year follow-up of a patient with leber congenital amaurosis and novel RPE65 mutations.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14611946 2003 Analysis of three genes in Leber congenital amaurosis in Indonesian patients.
12960219 2003 A Tyr368His RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12357075 2002 RPE65 gene: multiplex PCR and mutation screening in patients from India with retinal degenerative diseases.
11727200 2002 Retinal dystrophy due to paternal isodisomy for chromosome 1 or chromosome 2, with homoallelism for mutations in RPE65 or MERTK, respectively.
11462243 2001 Four novel mutations in the RPE65 gene in patients with Leber congenital amaurosis.
11095629 2000 Genetics and phenotypes of RPE65 mutations in inherited retinal degeneration.
10766140 2000 Mutation analysis of 3 genes in patients with Leber congenital amaurosis.
10386590 1999 Identification of RPE65 in transformed kidney cells.
10090910 1999 Different functional outcome of RetGC1 and RPE65 gene mutations in Leber congenital amaurosis.
9801879 Autosomal recessive retinal dystrophy associated with two novel mutations in the RPE65 gene.
9501877 1998 Promoter analysis of RPE65, the gene encoding a 61-kDa retinal pigment epithelium-specific protein.
9501220 1998 Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis.
9328280 1997 RPE65, the major retinal pigment epithelium microsomal membrane protein, associates with phospholipid liposomes.
9326941 1997 Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy.
9326927 1997 Mutations in RPE65 cause Leber's congenital amaurosis.
8474143 1993 A developmentally regulated microsomal protein specific for the pigment epithelium of the vertebrate retina.
8340400 1993 Molecular cloning and expression of RPE65, a novel retinal pigment epithelium-specific microsomal protein that is post-transcriptionally regulated in vitro.
8034329 1994 The gene for the retinal pigment epithelium-specific protein RPE65 is localized to human 1p31 and mouse 3.
7633413 1995 Molecular characterization of the human gene encoding an abundant 61 kDa protein specific to the retinal pigment epithelium.
1331074 1992 Characterization of a plasma retinol-binding protein membrane receptor expressed in the retinal pigment epithelium.