RPE65
Chr 1ARADretinoid isomerohydrolase RPE65
Also known as: BCO3, LCA2, RP20, mRPE65, p63, rd12, sRPE65
The protein encoded by this gene is a component of the vitamin A visual cycle of the retina which supplies the 11-cis retinal chromophore of the photoreceptors opsin visual pigments. It is a member of the carotenoid cleavage oxygenase superfamily. All members of this superfamily are non-heme iron oxygenases with a seven-bladed propeller fold and oxidatively cleave carotenoid carbon:carbon double bonds. However, the protein encoded by this gene has acquired a divergent function that involves the concerted O-alkyl ester cleavage of its all-trans retinyl ester substrate and all-trans to 11-cis double bond isomerization of the retinyl moiety. As such, it performs the essential enzymatic isomerization step in the synthesis of 11-cis retinal. Mutations in this gene are associated with early-onset severe blinding disorders such as Leber congenital. [provided by RefSeq, Oct 2017]
Primary Disease Associations & Inheritance
Clinical highlights
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
RPE65 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Gene Therapy in Subjects With Biallelic RPE65 Mutation-associated Retinal Dystrophy
RECRUITINGPhase 1 Follow-on Study of AAV2-hRPE65v2 Vector in Subjects With Leber Congenital Amaurosis (LCA) 2
ACTIVE NOT RECRUITINGAn Expanded Clinical Study Evaluating the AAV2-RPE65 Gene Therapy(LX101) in Patients With LCA
NOT YET RECRUITINGSafety and Tolerability of LX101 for Inherited Retinal Dystrophy Associated With RPE65 Mutations
ACTIVE NOT RECRUITINGEfficacy and Safety of LX101 for Inherited Retinal Dystrophy Associated With RPE65 Mutations
ACTIVE NOT RECRUITINGInherited Retinal Diseases: Natural History and Genotype-Phenotype Correlations
NOT YET RECRUITINGLeber Congenital Amaurosis Inherited Blindness of Gene Therapy Trial(LIGHT)
ACTIVE NOT RECRUITINGLong-term Follow-up Study in Subjects Who Received Voretigene Neparvovec-rzyl (AAV2-hRPE65v2)
ACTIVE NOT RECRUITINGSafety and Efficacy Trial of HG004 for Leber Congenital Amaurosis Related to Rpe65 Gene Mutations (STAR)
RECRUITINGSafety and Efficacy Study in Subjects With Leber Congenital Amaurosis
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools