OPN1MW

Chr XXLRX-linked

opsin 1, medium wave sensitive

ENSG00000268221 UniProt: P04001 OMIM: 300821

The encoded protein is a G-protein coupled receptor that functions as the medium-wavelength sensitive opsin (green cone photopigment), absorbing light to mediate color vision in retinal cone cells. Mutations cause X-linked recessive deutanopic colorblindness and blue cone monochromacy, predominantly through loss-of-function affecting normal color perception. The gene is located in a tandem array with other opsin genes on the X chromosome where unequal recombination and gene conversion frequently occur between these sequences.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

G protein-coupled photoreceptor that selectively activates G(i) proteins in response to medium-wavelength (green) light, thereby decreasing intracellular cAMP levels (PubMed:2937147, PubMed:6140680, Ref.6). Activation occurs 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 a G protein-mediated phototransduction cascade (Ref.6). Mediates visual perception of green light in cone photoreceptor cells (PubMed:12051694, PubMed:1302020, PubMed:8666378)

OMIM ResearchGenerating clinical summary…

MultiplemechanismXLR/X-linkedLOEUF 1.782 OMIM phenotypes

Clinical Summary— OPN1MW

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Gene-Disease Validity (ClinGen)

red-green color blindness · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.78LOEUF

pLI 0.038

Z-score 0.42

OE 0.73 (0.29–1.78)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.75Z-score

OE missense 0.69 (0.52–0.93)

32 obs / 46.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.73 (0.29–1.78)

0≤0.351.4

Missense OE?0.69 (0.52–0.93)

0≤0.61.4

Synonymous OE?1.65

0≤1.21.6

LoF obs/exp: 2 / 2.7Missense obs/exp: 32 / 46.3Syn Z: -2.35

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveOPN1MW-related blue cone monochromacyOTHERXLR

This gene — mechanism propensity

0.77top 25%

GOF

0.77top 25%

LOF

0.2970th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.