OPN1MW
protein-codingopsin 1, medium wave sensitive, the group of Opsin receptors
Gene summary
This gene encodes for a light absorbing visual pigment of the opsin gene family. The encoded protein is called green cone photopigment or medium-wavelength sensitive opsin. Opsins are G-protein coupled receptors with seven transmembrane domains, an N-terminal extracellular domain, and a C-terminal cytoplasmic domain. The long-wavelength opsin gene and multiple copies of the medium-wavelength opsin gene are tandemly arrayed on the X chromosome and frequent unequal recombination and gene conversion may occur between these sequences. X chromosomes may have fusions of the medium- and long-wavelength opsin genes or may have more than one copy of these genes. Defects in this gene are the cause of deutanopic colorblindness. [provided by RefSeq, Mar 2009]
- GCP
- CBBM
- CBD
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0010564
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: XL
Disease ID:MONDO:0010563
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0015993
Submitter: Orphanet
Inheritance Pattern: XL
Disease ID:MONDO:0010563
Submitter: Orphanet
Inheritance Pattern: XL
Disease ID:MONDO:0024458
Submitter: PanelApp Australia
Inheritance Pattern: XL
Disease ID:MONDO:0010563
Submitter: Ambry Genetics
Inheritance Pattern: XL
Disease ID:MONDO:0010564
Submitter: ClinGen
*OPN1MW* was first reported in relation to X-linked cases of blue cone monochromacy in 1989 (Nathans et al, PMID: 2788922), which was caused by a combined disruption of the red/green visual pigment gene array (later named *OPN1LW* and *OPN1MW*, respectively). Affected males had markedly impaired color vision, with or without reduced visual acuity, photophobia, and nystagmus. Electroretinogram showed normal rod and S cone function, but absent responses attributable to L and M cones. Subsequent publications starting in 1992 (Winderickx et al, PMID: 1302020) have described a more limited phenotype associated with monogenic disruption of the *OPN1MW* gene alone, characterized as deuteranomaly and/or deuteranopia. Per criteria outlined by the ClinGen Lumping & Splitting guidelines, this curation has focused on cases in which the cause of disease is monogenic *OPN1MW* loss-of-function, with the disease entity referred to as *OPN1MW*-related cone dysfunction. However, it is important to note the higher frequency and clinical importance of blue cone monochromacy resulting from digenic *OPN1LW* and *OPN1MW* loss-of-function variants. Three missense variants have been reported in 5 probands, and one variant located in the promoter region of the *OPN1MW* gene has been reported in 32 probands, across 4 publications (PMIDs: 1302020, 11772996, 12051694, 12626747). All of the probands scored in this curation were males who harbored the variant allele in the hemizygous state. Large families with co-segregation of the genotype with affected status were not found, so segregation evidence did not contribute to the scoring of the gene-disease relationship. Reports describing a strictly monogenic phenotype for *OPN1MW* remain limited, underscoring the greater clinical relevance of the digenic form involving both *OPN1MW* and **OPN1LW*. The curated evidence for the monogenic form reached a Moderate level of scoring and did not independently meet criteria for a Definitive classification. Therefore, the association was manually classified as Definitive in the broader clinical context. The mechanism of pathogenicity appears to be loss of function. This gene-disease association is also supported by experimental evidence indicating that *OPN1MW* encodes a medium-wave-sensitive opsin that enables photoperception of green-range wavelengths, consistent with patients’ lack of spectral sensitivity for green light when the gene is disrupted (PMID: 12051694). Functional assays in non-patient cells expressing the disease-associated variant p.Cys203Arg demonstrated protein misfolding, instability, and loss of normal opsin activity, including failure to absorb light at the appropriate wavelength and inability to activate transducin (PMID: 9152227). *OPN1MW* is highly specifically expressed in the human retina (PMID: 30239781). Although *OPN1MW* is a primate-specific gene, subretinal delivery of cone opsins in a mouse model of blue cone monochromacy restored cone outer segment structure and cone-mediated ERG responses, supporting the biological plausibility of therapeutic rescue (PMID: 28751656). The neighboring gene *OPN1LW* shares a similar function (encoding a long-wave-sensitive opsin that enables photoperception of red-range wavelengths), and its disruption similarly results in color vision defects (PMID: 9579484, PMID: 10191338, PMID: 15148406). In summary, *OPN1MW* is Definitively associated with *OPN1MW*-related cone dysfunction. This has been repeatedly demonstrated in both research and diagnostic settings, and has been upheld over time without the emergence of contradictory evidence, leading to a Definitive classification. This classification was approved by the ClinGen Retina Gene Curation Expert Panel on September 4th, 2025 (SOP Version 11).
Clinical Genomic Database (CGD)
Manifestation: Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to OPN1MW variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000513.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 3 | |||
| missense | 4 | 17 | 12 | 1 | 34 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 5 | 0 | 17 | 13 | 3 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000504.1 | 6 | MANE Select | |
| Ensembl | ENSP00000472316.1 | 6 | MANE Select | |
| Ensembl | ENSP00000469055.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- GPCRs, Class A Rhodopsin-like
- Signaling by GPCR
- Signal Transduction
- Opsins
- Class A/1 (Rhodopsin-like receptors)
Biological Process
- retinoid metabolic process
- G protein-coupled receptor signaling pathway
- visual perception
- phototransduction
- detection of visible light
Molecular Function
- G protein-coupled photoreceptor activity
- photoreceptor activity
- identical protein binding
Cellular Component
- photoreceptor outer segment
- plasma membrane
- integral component of plasma membrane
- photoreceptor disc membrane
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Visual pigments are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsin, covalently linked to cis-retinal. {ECO:0000305|PubMed:12051694, ECO:0000305|PubMed:1302020, ECO:0000305|PubMed:2937147}.;
- Disease
- DISEASE: Colorblindness, partial, deutan series (CBD) [MIM:303800]: A color vision defect characterized by a dichromasy in which red and green are confused, without loss of luminance or shift or shortening of the spectrum. Dichromasy is due to the use of only two types of photoreceptors, blue plus red in deuteranopia and blue plus green in protanopia. {ECO:0000269|PubMed:12051694, ECO:0000269|PubMed:1302020}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Blue cone monochromacy (BCM) [MIM:303700]: A rare X- linked congenital stationary cone dysfunction syndrome characterized by the absence of functional long wavelength- sensitive and medium wavelength-sensitive cones in the retina. Color discrimination is severely impaired from birth, and vision is derived from the remaining preserved blue (S) cones and rod photoreceptors. BCM typically presents with reduced visual acuity, pendular nystagmus, and photophobia. Patients often have myopia. {ECO:0000269|PubMed:8666378}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cone dystrophy 5 (COD5) [MIM:303700]: A X-linked cone dystrophy. Cone dystrophies are retinal dystrophies characterized by progressive degeneration of the cone photoreceptors with preservation of rod function, as indicated by electroretinogram. However, some rod involvement may be present in some cone dystrophies, particularly at late stage. Affected individuals suffer from photophobia, loss of visual acuity, color vision and central visual field. Another sign is the absence of macular lesions for many years. Cone dystrophies are distinguished from the cone-rod dystrophies in which some loss of peripheral vision also occurs. {ECO:0000269|PubMed:20579627}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.145
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |