RPE65 Gene: Retinoid Isomerase in Visual Cycle and Inherited Retinal Dystrophy
Comprehensive biomedical reference for RPE65: genomic context, protein function, disease associations, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | RPE65 |
|---|---|
| Full Name | Retinal pigment epithelium-specific 65 kDa protein |
| Gene Type | Protein coding |
| Chromosomal Location | 1p31.3 (GRCh38: chr1:68,428,822-68,449,275, minus strand) |
| NCBI Gene ID | 6121 ncbi.nlm.nih.gov/gene/6121 |
| Ensembl ID | ENSG00000116745 |
| UniProt ID | Q16518 |
| OMIM ID | 180069 |
| HGNC ID | 10294 |
| Aliases | LCA2, RP20, rd12, p63, mRPE65 |
Description
RPE65 encodes a 65-kDa protein predominantly expressed in the retinal pigment epithelium (RPE). It functions as an isomerohydrolase in the visual cycle, converting all-trans-retinyl esters to 11-cis-retinol, a critical step for regenerating the visual chromophore 11-cis-retinal. Mutations in RPE65 cause autosomal recessive early-onset severe retinal dystrophy, including Leber congenital amaurosis type 2 (LCA2) and retinitis pigmentosa type 20 (RP20). The gene is also a target for gene therapy (voretigene neparvovec).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Leber congenital amaurosis 2 (LCA2) | Loss-of-function mutations in RPE65 disrupt the isomerohydrolase activity, leading to impaired 11-cis-retinal regeneration and photoreceptor degeneration. | OMIM #204100; ClinVar; multiple pathogenic variants documented |
| Retinitis pigmentosa 20 (RP20) | Biallelic mutations cause progressive rod-cone dystrophy due to visual cycle failure. | OMIM #613794; ClinVar |
| Early-onset severe retinal dystrophy (EOSRD) | RPE65 mutations are a common cause of EOSRD, with variable severity. | ClinVar; literature (e.g., den Hollander et al., 2008) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Retinal pigment epithelium | Not available (GTEx lacks RPE) | High (specific) |
| Testis | 0.4 | Low |
| Brain (cerebellum) | 0.2 | Low |
| Other tissues | 0.0-0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (RPE cell line) | Not available | Endogenous expression; used in RPE studies |
| HeLa | 0.0 | No expression |
| HepG2 | 0.0 | No expression |
| K562 | 0.0 | No expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.11+2T>A (IVS1+2T>A) | Splice donor | Common in North American LCA patients | Splice defect leading to loss of function |
| p.Arg91Trp (c.271C>T) | Missense | Found in various populations; pathogenic | Reduced enzymatic activity |
| p.Leu408Pro (c.1223T>C) | Missense | Reported in LCA | Disrupts protein folding/function |
| p.Tyr368Ter (c.1104C>A) | Nonsense | Rare | Premature truncation, loss of function |
| p.Glu417Gln (c.1249G>C) | Missense | Reported in RP | Impaired isomerase activity |
Mutation functional classification
Loss of Function (LOF)
Most RPE65 mutations are loss-of-function, leading to reduced or absent isomerohydrolase activity, causing retinal dystrophy.
Gain of Function (GOF)
No gain-of-function mutations reported; RPE65 is not known to act as an oncogene.
Dominant Negative (DN)
No dominant-negative mechanism; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Visual cycle (retinoid metabolism)
• Retinol metabolism (KEGG: hsa00830)
• Vitamin A metabolism
Protein Summary
RPE65 is a 533-amino acid protein (UniProt Q16518) localized to the endoplasmic reticulum membrane of retinal pigment epithelium cells. It binds all-trans-retinyl esters and catalyzes the conversion to 11-cis-retinol via a ferrous iron-dependent isomerohydrolase mechanism. The protein is essential for vision; its deficiency leads to accumulation of retinyl esters and lack of 11-cis-retinal, causing photoreceptor degeneration. RPE65 is also a target for gene therapy (Luxturna).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RPE65 Knockout HEK293 Cell Line | EDJ-KQ2185 | Human | 6121 | Details Get a Quote |
| RPE65 Knockout HeLa Cell Line | EDJ-KQ54339 | Human | 6121 | Details Get a Quote |
| RPE65 Knockout A-549 Cell Line | EDJ-KQ62835 | Human | 6121 | Details Get a Quote |
| RPE65 Knockout HCT 116 Cell Line | EDJ-KQ71301 | Human | 6121 | Details Get a Quote |
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