GENE REFERENCE / HGNC:10294

RPE65

retinoid isomerohydrolase RPE65

protein-coding gene1p31.3Gene information

What does this gene do?

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 RPE layer is essential for capturing light and vision.

The RPE65 protein is involved in a multi-step process called the visual cycle (also called the retinoid or vitamin A 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 is a key enzyme in this cycle as it converts all-trans retinal to 11-cis retinol. Other enzymes then produce 11-cis retinal, so that the visual cycle can begin again and capture light.

Source: MedlinePlus, National Library of Medicine. Source publication: 2022-10-06. Source review: 2022-10.

ClinGen reviews

ClinGen reviews the evidence linking a particular gene to a condition. Each rating below describes the strength of that link. It does not classify a variant in your DNA file.

Condition	Inheritance	Evidence
RPE65-related recessive retinopathyMONDO:0100368 · Evaluated 2022-05-24	Autosomal recessive	DefinitiveRetina Gene Curation Expert Panel
RPE65-related dominant retinopathyMONDO:0100452 · Evaluated 2022-02-07	Autosomal dominant	StrongRetina Gene Curation Expert Panel

ClinVar records

These numbers show what has been submitted to ClinVar. They cannot tell you how likely you are to have a condition.

Submitted alleles: 1,224
Submissions for variants in or overlapping this gene: 2,604
Submissions explicitly reporting this gene: 2,533
Alleles reported pathogenic / likely pathogenic: 402
VariationIDs with uncertain significance: 378
VariationIDs with conflicting classifications: 25

The rows count different things: alleles, submissions or VariationIDs. Their categories can overlap, so do not add them together. Pathogenic/likely pathogenic counts exclude structural variants that merely overlap a gene. A dash in the source means “not reported,” not zero.

NCBI produces the gene-summary file each week using counts recorded at the start of the month. The numbers may differ from those on the live ClinVar website. Read the field definitions ↗

View this gene in ClinVar ↗

YOUR DNA FILE

Can your DNA file tell you about RPE65?

From a DNA test kit (such as 23andMe, AncestryDNA or MyHeritage). These kits check a fixed list of about 600,000 to 700,000 positions across your whole genome. ClinVar lists 402 alleles in RPE65 reported as pathogenic or likely pathogenic. A kit checks only some of these positions, and often none of them.

From whole genome sequencing (a VCF file). Sequencing reads most of your genome. Your file lists the places where your DNA differs from the reference genome. Some regions are hard to sequence, including parts of some genes that have near-identical copies elsewhere, and a VCF file does not record which positions were read well.

If a variant is not in your file, that does not mean you don’t have it.

What BioDecode checks

BioDecode compares every variant in your file with ClinVar, on your own computer. For each match, it shows the ClinVar classification, the review status and the condition it was reported for. Your file is not uploaded.

A ClinVar classification applies to one particular variant and the condition it was reported for. It does not tell you about other variants in RPE65.

BioDecode cannot fill gaps in your test, diagnose a condition or replace clinical testing.

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