OPN1LW

Chr XXLRX-linked

opsin 1, long wave sensitive

NCBI Gene: 5956 ENSG00000102076 UniProt: P04000 OMIM: 300822

The protein is a red cone photopigment that functions as a G-protein coupled receptor to absorb long-wavelength light and mediate color vision. Mutations cause X-linked recessive blue cone monochromacy and protan colorblindness through loss of red cone function. The gene shows high constraint against loss-of-function variants, consistent with haploinsufficiency being the primary disease mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

G protein-coupled photoreceptor that selectively activates transducin G alpha protein (G(t)) in response to long-wavelength (red) light (PubMed:21314100, PubMed:2937147, PubMed:6140680). This activation leads to increased cGMP phosphodiesterase activity, resulting in decreased intracellular cGMP and subsequent closure of cGMP-gated ion channels (PubMed:21314100, PubMed:2937147, PubMed:6140680). The process is initiated when the opsin-bound cis-retinal chromophore absorbs a photon and isomerizes to all-trans-retinal, inducing a conformational change in the opsin that triggers the G protein-mediated phototransduction cascade (PubMed:21314100, PubMed:2937147, PubMed:6140680). Mediates visual perception of red light in cone photoreceptor cells (PubMed:12051694, PubMed:8213841, PubMed:8666378)

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Blue cone monochromacyMIM #303700

XLR

Colorblindness, protanMIM #303900

X-linked

UniProtColorblindness, partial, protan series

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · red color blindness · XL · ClinGen 2025

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.26

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

GeneReview available — OPN1LW

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

LoF Constraint?

0.26LOEUF

pLI 0.975

Z-score 3.13

OE 0.00 (0.00–0.26)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.47Z-score

OE missense 0.89 (0.77–1.03)

126 obs / 141.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.26)

0≤0.351.4

Missense OE?0.89 (0.77–1.03)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 0 / 11.4Missense obs/exp: 126 / 141.6Syn Z: -0.19

Background carrier burden — how many people carry a rare variant somewhere in OPN1LW?

gnomAD v4 · ~729k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

182 rare PASS variants

Rare truncating (LoF)

1 in 29,000

7 rare PASS variants

Rare synonymous (reference)

1 in 330

97 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for OPN1LW. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~560k	1 in 190	1 in 30,000
South Asian	~36k	1 in 180	none seen
Remaining (unassigned)	~31k	1 in 160	≈ 1 in 31,000
European (Finnish)	~27k	1 in 290	≈ 1 in 27,000
Admixed American	~23k	1 in 260	none seen
African / African American	~20k	1 in 190	≈ 1 in 20,000
East Asian	~20k	1 in 130	none seen
Ashkenazi Jewish	~13k	1 in 450	none seen
Middle Eastern	~2,736	1 in 260	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 6 coding exons well covered in gnomAD exomes; exons 3, 6 poorly covered. Genomes: 1 of 6 (exons 1, 2, 3, 4, 6 below).? see exons ↓