OPN4 (Melanopsin) Gene: Function, Expression, and Clinical Significance
A comprehensive biomedical overview of the OPN4 gene, encoding melanopsin, a key photopigment in non-image-forming vision.
Gene Information Card
| Symbol | OPN4 |
|---|---|
| Full Name | opsin 4 |
| Gene Type | protein coding |
| Chromosomal Location | 10q23.2 |
| NCBI Gene ID | 94233 ncbi.nlm.nih.gov/gene/94233 |
| Ensembl ID | ENSG00000122375 |
| UniProt ID | Q9UHM6 |
| OMIM ID | 606665 |
| HGNC ID | 14412 |
| Aliases | MOP, melanopsin |
Description
The OPN4 gene encodes melanopsin, a light-sensitive G-protein-coupled receptor (GPCR) expressed in a subset of retinal ganglion cells known as intrinsically photosensitive retinal ganglion cells (ipRGCs). Melanopsin is the primary photopigment mediating non-image-forming visual functions, including circadian photoentrainment, pupillary light reflex, and regulation of sleep-wake cycles. It is maximally sensitive to blue light (~480 nm).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Seasonal Affective Disorder (SAD) | Altered melanopsin function may affect light-induced phase shifting and mood regulation, contributing to SAD susceptibility. | Association studies (e.g., Roecklein et al., 2009) suggest OPN4 variants influence SAD risk. |
| Non-24-Hour Sleep-Wake Disorder | Reduced melanopsin signaling can impair circadian entrainment to light-dark cycles, leading to free-running rhythms. | Case reports and functional studies in blind individuals with intact ipRGCs show residual light responses. |
| Pupillary Light Reflex Defects | Loss of melanopsin function reduces sustained pupillary constriction, especially under bright light. | Studies in OPN4 knockout mice and human genetic variants demonstrate impaired pupillary responses. |
| Glaucoma | Melanopsin-expressing ipRGCs are susceptible to damage in glaucoma, contributing to circadian disruption. | Histological studies show loss of ipRGCs in glaucomatous retinas. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Retina | Not available (nTPM not provided) | High expression in ipRGCs |
| Brain | Not available | Low expression in some hypothalamic regions (projections) |
| Skin | Not available | Low expression in keratinocytes (reported in some studies) |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 (transfected) | Not applicable | Used for functional studies of melanopsin phototransduction |
| SH-SY5Y (neuroblastoma) | Not available | Endogenous expression reported in some studies |
| Retinal ganglion cells (primary) | Not available | Native expression in ipRGCs |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1079610 (P394L) | Missense | Allele frequency ~0.2-0.3 in European populations | Altered melanopsin function; associated with SAD in some studies |
| rs268634 (T10M) | Missense | Rare | Potential effect on protein stability; clinical significance uncertain |
| rs267570 (A45T) | Missense | Rare | Functional impact not fully characterized |
Mutation functional classification
Loss of Function (LOF)
Complete loss-of-function mutations in OPN4 are rare; animal models show disrupted circadian photoentrainment and pupillary reflexes.
Gain of Function (GOF)
No clear gain-of-function mutations reported; some variants may alter spectral sensitivity or kinetics.
Dominant Negative (DN)
No evidence for dominant-negative effects; melanopsin functions as a monomeric GPCR.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • photoreceptor activity |
| • light-activated channel activity | • signal transduction |
| • response to light stimulus | • circadian rhythm |
| • phototransduction | • membrane |
Pathways
• Melanopsin-mediated phototransduction
• Circadian entrainment
• Pupillary light reflex
Protein Summary
Melanopsin is a 534-amino acid protein with seven transmembrane domains, belonging to the opsin family. It is expressed in ipRGCs and uses a unique phototransduction cascade involving Gq/11 proteins, phospholipase C, and TRPC channels, leading to depolarization. It exhibits bistable photopigment properties, regenerating its chromophore (11-cis retinal) via light absorption.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OPN4 Knockout HEK293 Cell Line | EDJ-KQ11303 | Human | 94233 | Details Get a Quote |
| OPN4 Knockout HeLa Cell Line | EDJ-KQ57886 | Human | 94233 | Details Get a Quote |
| OPN4 Knockout A-549 Cell Line | EDJ-KQ66381 | Human | 94233 | Details Get a Quote |
| OPN4 Knockout HCT 116 Cell Line | EDJ-KQ74805 | Human | 94233 | Details Get a Quote |
| OPN4 and NFATC1 Overexpression HEK293 Stable Cell Line | EDC90142 | Human | 94233 & 4772 | Details Get a Quote |
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