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Canine gene

RPE65

Human counterpart: RPE65

RPE65 is a gene catalogued in the canine genome. Below are the inherited conditions OMIA links to it in dogs, its human counterpart, and its canonical records across the genomics world.

Conditions linked to this gene

The inherited conditions OMIA associates with RPE65 in dogs. Each links to the full record.

In the reference databases

RPE65 as it is catalogued across the genomics world. Each link is the canonical record, so this gene composes with everything those resources know.

The human counterpart

In humans, this gene's counterpart is RPE65. That ortholog is what connects RPE65 to a century of human medical genetics. The dog and human proteins are 99% identical.

In people, RPE65 appears tolerant of loss-of-function variation (gnomAD v4.1 constraint, LOEUF 1.00). Constraint measures intolerance to loss-of-function only and does not indicate importance; some tolerant genes cause disease through other mechanisms.

In people, variants in the RPE65 gene are classified as pathogenic in ClinVar for 1 expert-reviewed condition.

In dogs, 16 of 1,482 Dog10K variants in this gene sit at a position kept conserved across 241 mammals (the exhaustive scan), candidates worth a closer look, never a diagnosis.

Translational evidence balance
balanced · 0

Dog and human evidence are symmetric here, a validated cross-species footprint. Coverage, not importance. D = 1 dog vs H = 1 human cited disease channels.

Medicine face

Q1 · both planes filled

RPE65

Two planes on one gene. Disagreement is the reading, not a hole to fill.A teaching case. Both the canine evidence plane and the human medicine plane hold a row.

Canine plane

Coverage

answered

lit_all

Spectra

6 named streams agree. A recount, not a medicine vote.

Open Spectra

Lookup · Discovery · Frontier

Lookup cleared. Discovery recovered known. A candidate never fills a drug row. Frontier is not the subject here.

Medicine plane

Mechanism

Critical isomerohydrolase in the retinoid cycle involved in regeneration of 11-cis-retinal, the chromophore of rod and cone opsins.

Full function description, 6 more sentences
  • Catalyzes the cleavage and isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol which is further oxidized by 11-cis retinol dehydrogenase to 11-cis-retinal for use as visual chromophore.
  • Essential for the production of 11-cis retinal for both rod and cone photoreceptors.
  • Also capable of catalyzing the isomerization of lutein to meso-zeaxanthin an eye- specific carotenoid.
  • The soluble form binds vitamin A (all-trans-retinol), making it available for LRAT processing to all- trans-retinyl ester.
  • The membrane form, palmitoylated by LRAT, binds all-trans-retinyl esters, making them available for IMH (isomerohydrolase) processing to all-cis-retinol.
  • The soluble form is regenerated by transferring its palmitoyl groups onto 11-cis-retinol, a reaction catalyzed by LRAT (By similarity).

Source UniProt via Open Targets · PMID 16116091 · PMID 17848510 · PMID 28874556

The canonical retinoid cycle in rods (twilight vision) · Reactome

The cited mechanism chain, the labeled product, and the construct receipts are below on this page.

Molecules

  • Luxturna, generically Voretigene Neparvovec-Rzyl

    FDA label

    EXOGENOUS GENE · Action on the human target as recorded by the cited medicine-plane source. Not a canine treatment claim and not a disease-direction claim.

    FDA 19 December 2017 · label

Emixustat acts on this protein and is labeled for other conditions. Acting on a protein is not treating a disease of it.

Canine trials

unqueryable

We hold no canine registry row. The AVMA Veterinary Clinical Trials Registry is the index that would hold one. This station is unqueryable until that ingest exists. That is not evidence that nobody runs trials in dogs.

PK / tox station

stub

This station is not wired. No PK or tox numbers.

Acland 2001 used canine RPE65 cDNA. That construct is not the labeled human product.

This is not a treatment recommendation and not a claim about any individual dog.

Molecule direction and mechanism of action include ChEMBL (CC BY-SA 3.0).

Coverage · Spectra · Frontier

The mechanism

Why this canine condition is studied

  1. 1 RPE65 is the isomerohydrolase of the retinoid cycle.
  2. 2 When it fails, the cycle stalls.
  3. 3 11-cis-retinal is not made.
  4. 4 Photoreceptors lose function.

An approved human product restores that cycle in people who meet the label. Dogs with this condition are a natural model of that mechanism. They are not human patients, and a pet Briard does not have Leber congenital amaurosis 2.

In people, the analog is Leber congenital amaurosis 2 (MONDO:0008765). The canine condition models that human disease. It is not the same diagnosis.

Labeled human product

The labeled human product is Luxturna, generically voretigene neparvovec-rzyl (AAV2-hRPE65v2), approved by the FDA on 19 December 2017 for people with biallelic RPE65 mutation-associated retinal dystrophy who have viable retinal cells. FDA label. This page does not recommend treatment for any dog.

Construct. The 2001 canine study used canine RPE65 cDNA. That construct is not the labeled human product. The labeled product uses a human-optimized RPE65 cDNA. Acland et al. 2001, Nature Genetics (PMID 11326284) ; Bennicelli 2008, Molecular Therapy ; Maguire 2008, New England Journal of Medicine ; Russell 2017, Lancet .

What still happens. Function can rise while degeneration continues. A measured improvement in vision is not the same as a halt to the underlying loss of photoreceptors. Cideciyan et al. 2013, PNAS (PMID 23341635) .

Research tools for this gene
Dog10K lookup Candidate models AVCG classification table

Lookup and discovery are candidate-framed research surfaces. Classification renders AVCG grades we cite; Sniff does not score variants with a model of its own.

On the numbers

Per-breed allele frequencies across the atlas are surfaced for the trait loci Sniff has verified a direction-of-effect for. For RPE65 we show the cited identity and disease associations, and we would rather show you exactly that than a frequency we cannot yet interpret honestly. See the gene catalog for trait loci with frequency views and every disease-linked gene page.

How to cite this page

Gene identity and disease associations are grounded in OMIA (CC-BY) and the open Sniff Atlas. Full citation formats at sniff.world/cite.

Last updated
Sources: OMIA · Sniff gene crossrefs · Ensembl / NCBI / HGNC · gnomAD v4.1 (Karczewski 2020) · ClinVar (Landrum 2018) · Dog10K (Meadows 2023) · Zoonomia 241-way phyloP (Christmas 2023)