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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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OPN4
opsin 4
Chromosome 10 · 10q23.2
NCBI Gene: 94233Ensembl: ENSG00000122375.13HGNC: HGNC:14449UniProt: Q9UHM6
61PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
G protein-coupled photoreceptor activityphototransduction11-cis retinal bindingplasma membraneconjunctival disorderresponse to xenobiotic stimulushypertensionalcohol drinking
✦AI Summary

OPN4 encodes melanopsin, a G protein-coupled photoreceptor that serves as the primary mediator of non-image forming responses to light. The protein functions by binding cis-retinaldehydes and exhibiting peak sensitivity around 480 nm blue light 1. OPN4 operates through multiple G protein signaling pathways, including canonical Gq activation and robust Gi/Gβγ signaling, which may explain its functional diversity 2. The receptor is expressed in photosensitive retinal ganglion cells and plays crucial roles in circadian photoentrainment, pupillary light reflexes, and sleep/wake timing regulation 13. Genetic polymorphisms in OPN4, particularly I394T, P10L, and R168C variants, are associated with altered light sensitivity, sleep disorders, and seasonal affective disorder 43. Beyond the retina, OPN4 is expressed in choroidal nerve fibers, intrinsic neurons, and melanocytes, suggesting broader physiological roles 5. Recent research demonstrates that modified OPN4 can be used optogenetically to induce hibernation-like states in mice 6, and near-infrared light activation of OPN4 promotes hippocampal neurogenesis with anxiolytic effects 7. The protein's diverse signaling capabilities and widespread expression pattern support its fundamental role in light-mediated physiological processes.

Sources cited
1
OPN4 peak sensitivity around 480 nm and role in circadian photoentrainment
PMID: 32708259
2
OPN4 signals through multiple G protein pathways including Gq and Gi/Gβγ
PMID: 29712722
3
I394T polymorphism association with sleep/wake timing
PMID: 24887407
4
OPN4 polymorphisms linked to sleep disorders and seasonal affective disorder
PMID: 40556870
5
OPN4 expression in choroidal structures beyond retinal ganglion cells
PMID: 39151779
6
Modified OPN4 used optogenetically to induce hibernation-like states
PMID: 36452866
7
NIR light activation of OPN4 promotes neurogenesis and anxiolytic effects
PMID: 39707549
Disease Associationsⓘ20
conjunctival disorderOpen Targets
0.40Weak
response to xenobiotic stimulusOpen Targets
0.23Weak
hypertensionOpen Targets
0.23Weak
alcohol drinkingOpen Targets
0.18Weak
glaucomaOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.05Suggestive
Parkinson diseaseOpen Targets
0.05Suggestive
spinocerebellar ataxia type 11Open Targets
0.04Suggestive
Alzheimer diseaseOpen Targets
0.04Suggestive
Spectrin-associated autosomal recessive cerebellar ataxiaOpen Targets
0.04Suggestive
spinocerebellar ataxia type 26Open Targets
0.04Suggestive
central nervous system cancerOpen Targets
0.04Suggestive
autosomal recessive spinocerebellar ataxia 15Open Targets
0.04Suggestive
atrial fibrillationOpen Targets
0.04Suggestive
spinocerebellar ataxia 27AOpen Targets
0.04Suggestive
leukodystrophy, hypomyelinating, 16Open Targets
0.04Suggestive
melanomaOpen Targets
0.03Suggestive
myoclonus-dystonia syndromeOpen Targets
0.03Suggestive
spinocerebellar ataxia type 15/16Open Targets
0.03Suggestive
autosomal recessive spinocerebellar ataxia 14Open Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CNGA3Protein interaction91%GNAT1Protein interaction91%GNAT2Protein interaction91%RPE65Protein interaction91%LRATProtein interaction91%AANATProtein interaction86%
Tissue Expression6 tissues
Heart
100%
Brain
23%
Ovary
3%
Lung
2%
Liver
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
OPN4CNGA3GNAT1GNAT2RPE65LRATAANAT
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9UHM6
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.15LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.90 [0.70–1.15]
RankingsWhere OPN4 stands among ~20K protein-coding genes
  • #7,588of 20,598
    Most Researched61
  • #11,966of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedOPN4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Human melanopsin (OPN4) gene polymorphisms: a systematic review.
PMID: 40556870
Front Neurosci · 2025
1.00
2
Association between the melanopsin gene polymorphism OPN4*Ile394Thr and sleep/wake timing in Japanese university students.
PMID: 24887407
J Physiol Anthropol · 2014
0.90
3
Optogenetic induction of hibernation-like state with modified human Opsin4 in mice.
PMID: 36452866
Cell Rep Methods · 2022
0.80
4
Near-infrared light induces neurogenesis and modulates anxiety-like behavior.
PMID: 39707549
Stem Cell Res Ther · 2024
0.70
5
Total Osteopontin and Its Isoform OPN4 Are Differently Expressed in Respiratory Samples during Influenza A(H1N1)pdm09 Infection and Progression.
PMID: 37317323
Microorganisms · 2023
0.60