OPN1LW

protein-coding

opsin 1, long 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 red cone photopigment or long-wavelength sensitive opsin. Opsins are G-protein coupled receptors with seven transmembrane domains, an N-terminal extracellular domain, and a C-terminal cytoplasmic domain. This gene and 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 partial, protanopic colorblindness. [provided by RefSeq, Jul 2008]

Previous symbols:

CBBM
RCP
CBP

MANE transcript

NM_020061.6

Inheritance

AD, XL, XL (involving both OPN1 genes)

ClinVar variants

P:10U:29B:9

Top phenotype

Colorblindness, partial, protan series; Blue cone monochromacy; Red cone polymorphism

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:154,144,243-154,159,032

External References & Databases

Ensembl (ENSG00000102076)

Transcript & Mutation Effects

hg38 • Region Span ~14.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cone-rod dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015993

Submitter: Orphanet

red color blindnessSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010565

Submitter: Labcorp Genetics (formerly Invitae)

red color blindnessDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010565

Submitter: ClinGen

Variants in the *OPN1LW* gene were first reported in 1993 in relation to X-linked cases of blue cone monochromacy caused by combined disruption of the *OPN1LW* and *OPN1MW* genes (Nathans et al., PMID: 8213841). Affected individuals exhibit color deficiency with absence of L- and M-cone function and reduced cone electroretinogram (ERG) responses with preservation of the short-wave S-cone ERG, accompanied by reduced visual acuity, myopia, nystagmus and/or photoaversion. Subsequent publications starting in 2002 have revealed a more limited phenotype associated with monogenic disruption of *OPN1LW* alone, which generally consists of protan color deficiency with absence of L-cone function, mildly to moderately reduced cone ERG responses, childhood-onset high myopia, and subnormal visual acuity (PMID: 12051694). The spectrum of disease has been asserted to include cases of early-onset high myopia in the absence of protan vision defects (PMID: 37097228). However, this emerging assertion may require support from additional research due to the high frequency of myopia in general, so has not been considered in this curation. Per criteria outlined by the ClinGen Lumping & Splitting Working Group, this curation has focused on cases in which the cause of disease is monogenic *OPN1LW* loss-of-function, with the disease entity referred to as *OPN1LW*-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. Eight suspected disease-causing variants were scored as part of this curation (three nonsense, four frameshift, and one missense), which have been collectively reported in eight probands from five different sources (PMID: 12051694, PMID: 26114493, PMID: 37097228, PMID: 40227176). One of the probands scored in this curation is unpublished but comes from a detailed ClinVar submission (SCV004176720.2). 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. This gene-disease association is also supported by experimental evidence indicating that *OPN1LW* encodes a long-wave-sensitive opsin that enables photoperception of red wavelengths (PMID: 9579484, PMID: 10191338), consistent with patients’ lack of spectral sensitivity for red light (PMID: 15148406). The neighboring gene *OPN1MW* shares a similar function (encoding a medium-wave-sensitive opsin that enables photoperception of green-range wavelengths), and its disruption similarly results in color vision defects (PMID: 1302020). *OPN1LW* is highly specifically expressed in the human retina and found in the retinal pigment epithelium (PMID: 30239781), and some disease-associated *OPN1LW* variants exhibit reduced abundance at the mRNA level when exogenously expressed (PMID: 30996587). While *OPN1LW* is a primate-specific gene, subretinal injection of virally packaged human *OPN1LW* into young *Opn1mw−/−/Opn1sw−/−* mice has the ability to promote cone outer segment regeneration and rescue cone functions such as the b-wave amplitude of the long wavelength-mediated ERG response and visually guided behavior (PMID: 35272502). Similarly, male squirrel monkeys lacking an intact *OPN1LW* locus gained red wavelength sensitivity following *OPN1LW* gene therapy and acquired the ability to access color vision-based food rewards (PMID: 19759534). In summary, *OPN1LW* is definitively associated with *OPN1LW*-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).

blue cone monochromacyMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010563

Submitter: PanelApp Australia

blue cone monochromacySUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010563

Submitter: Orphanet

blue cone monochromacyDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010563

Submitter: G2P

Clinical Genomic Database (CGD)

Colorblindness, partial, protan series; Blue cone monochromacy; Red cone polymorphismXL (involving both OPN1 genes)

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

Refs: 2847528; 2788922; 1881435; 1415215; 1302020; 8213841; 8792812; 10982039; 11772996; 12051694; 20579627; 23139274

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to OPN1LW variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 25

not providedTotal: 18

Cone monochromatismTotal: 7

Protan defectTotal: 3

X-linked cone dysfunction syndrome with myopiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020061.6. 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			2 clinvar	2 clinvar	1 clinvar	5
missense	3 clinvar		27 clinvar	4 clinvar	2 clinvar	36
nonsense	4 clinvar	1 clinvar				5
start loss						0
frameshift		2 clinvar				2
splice donor/acceptor (+/-2bp)						0
Total	7	3	29	6	3	48

Highest pathogenic variant AF is 9.289088e-7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020061.6	RefSeq	NP_064445.2	6	MANE Select
ENST00000369951.9	Ensembl	ENSP00000358967.4	6	MANE Select
ENST00000442922.1	Ensembl	ENSP00000402493.1	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
signal transduction
G protein-coupled receptor signaling pathway
visual perception
phototransduction

Molecular Function

G protein-coupled photoreceptor activity
photoreceptor activity

Cellular Component

photoreceptor outer segment
integral component of plasma membrane
photoreceptor disc membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369951
Coding exons: 6
Length: 14810
Individuals with no LoFs: 124091
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 124092
p: 0.00000403

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.466	126	142	0.890	0.0000121	2367
Missense (PolyPhen)		44	67.148	0.65527		1080
Synonymous	-0.186	65	63.1	1.03	0.00000621	724
Loss of Function	3.13	0	11.4	0.00	8.02e-7	171

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000072	0.000055	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Visual pigments are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsin, covalently linked to cis-retinal.;
Disease: DISEASE: Colorblindness, partial, protan series (CBP) [MIM:303900]: A color vision defect characterized by a dichromasy in which red and green are confused, with loss of luminance and shift of brightness and hue curves toward the short wave end 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}. 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:8213841, ECO:0000269|PubMed:8666378}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

RVIS EVS: 0.84
RVIS percentile EVS: 88.3

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.675

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium