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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RDH8
retinol dehydrogenase 8
Chromosome 19 · 19p13.2
NCBI Gene: 50700Ensembl: ENSG00000080511.5HGNC: HGNC:14423UniProt: K7ELF7
18PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
retinol metabolic processcytosolall-trans-retinol dehydrogenase (NAD+) activitysteroid biosynthetic processneurodegenerative diseaseParkinson diseaselysosomal storage diseasemultiple sclerosis
✦AI Summary

RDH8 (retinol dehydrogenase 8) is a visual cycle enzyme that reduces all-trans-retinal to all-trans-retinol with a clear preference for NADP cofactor 1. The protein plays a critical protective role in retinal health by facilitating clearance of toxic all-trans-retinal, particularly under high light conditions 2. RDH8 works in conjunction with ABCA4 and RDH12 to prevent accumulation of all-trans-retinal and its condensation products like A2E, which are associated with retinal degeneration 2. Loss of RDH8 function leads to delayed all-trans-retinal clearance, resulting in A2E accumulation in the retinal pigment epithelium (RPE) and subsequent ferroptosis - an iron-dependent form of cell death characterized by lipid peroxidation 34. Studies using Abca4-/-Rdh8-/- double knockout mice demonstrate progressive retinal degeneration under light exposure, serving as models for Stargardt disease and dry age-related macular degeneration 5. The first human case of biallelic RDH8 mutations causing autosomal recessive Stargardt macular dystrophy was recently reported, confirming the gene's clinical relevance 6. These findings establish RDH8 as essential for visual cycle homeostasis and retinal protection against light-induced damage.

Sources cited
1
RDH8 reduces all-trans-retinal to all-trans-retinol and genetic variation analysis
PMID: 14661078
2
RDH8 protects retina by facilitating all-trans-retinal clearance and reducing A2E production
PMID: 19553623
3
RDH8 deficiency leads to A2E accumulation and ferroptosis in RPE cells
PMID: 39984833
4
All-trans-retinal accumulation triggers ferroptosis in RPE, mitigated by ferroptosis inhibitors
PMID: 41094540
5
Abca4-/-Rdh8-/- mice serve as models for Stargardt disease and dry AMD with retinal degeneration
PMID: 39643129
6
First report of biallelic RDH8 mutations causing autosomal recessive Stargardt macular dystrophy in humans
PMID: 37628710
Disease Associationsⓘ21
neurodegenerative diseaseOpen Targets
0.36Weak
Alzheimer diseaseOpen Targets
0.29Weak
lysosomal storage diseaseOpen Targets
0.29Weak
multiple sclerosisOpen Targets
0.29Weak
Parkinson diseaseOpen Targets
0.29Weak
corneal degenerationOpen Targets
0.03Suggestive
keratoconusOpen Targets
0.03Suggestive
osteoarthritis, kneeOpen Targets
0.03Suggestive
HerniaOpen Targets
0.03Suggestive
hypertensionOpen Targets
0.02Suggestive
atrial fibrillationOpen Targets
0.02Suggestive
breast carcinomaOpen Targets
0.01Suggestive
retinal degenerationOpen Targets
0.01Suggestive
myopiaOpen Targets
0.01Suggestive
essential hypertensionOpen Targets
0.01Suggestive
Stargardt diseaseOpen Targets
0.01Suggestive
age-related macular degenerationOpen Targets
0.01Suggestive
dry age related macular degenerationOpen Targets
0.01Suggestive
gastric cancerOpen Targets
0.01Suggestive
ulcerative colitisOpen Targets
0.01Suggestive
Stargardt disease 5UniProt
Pathogenic Variants1
NM_015725.4(RDH8):c.262+1G>APathogenic
Stargardt disease 5|Melanoma
☆☆☆☆2025
View on ClinVar ↗
Related Genes
BCO1Protein interaction95%ALDH1A1Protein interaction94%ALDH1A3Protein interaction94%CYP26A1Protein interaction94%PNPLA4Protein interaction94%DGAT1Protein interaction94%
Tissue Expression6 tissues
Brain
100%
Lung
0%
Bone Marrow
0%
Heart
0%
Ovary
0%
Liver
0%
Gene Interaction Network
Click a node to explore
RDH8BCO1ALDH1A1ALDH1A3CYP26A1PNPLA4DGAT1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9NYR8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.07LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.71 [0.49–1.07]
RankingsWhere RDH8 stands among ~20K protein-coding genes
  • #14,789of 20,598
    Most Researched18
  • #5,403of 5,498
    Most Pathogenic Variants1
  • #10,795of 17,882
    Most Constrained (LOEUF)1.07
Genes detectedRDH8
Sources retrieved10 papers
Response time—
📄 Sources
10â–¼
1
Exposure of A2E to blue light promotes ferroptosis in the retinal pigment epithelium.
PMID: 39984833
Cell Mol Biol Lett · 2025
1.00
2
Using denaturing HPLC for SNP discovery and genotyping, and establishing the linkage disequilibrium pattern for the all-trans-retinol dehydrogenase (RDH8) gene.
PMID: 14661078
J Hum Genet · 2004
0.90
3
Inhibition of JNK signaling attenuates photoreceptor ferroptosis caused by all-trans-retinal.
PMID: 39643129
Free Radic Biol Med · 2025
0.80
4
A Splicing Variant in RDH8 Is Associated with Autosomal Recessive Stargardt Macular Dystrophy.
PMID: 37628710
Genes (Basel) · 2023
0.70
5
Ferrostatin-1, a ferroptosis inhibitor, mitigates all-trans-retinal-induced retinal pigment epithelium degeneration in mice.
PMID: 41094540
J Transl Med · 2025
0.60