OPN1MW2

Chr X

opsin 1, medium wave sensitive 2

Also known as: GOP

NCBI Gene: 728458 ENSG00000166160 UniProt: P0DN77

The encoded protein is a G-protein coupled receptor that functions as green cone photopigment (medium-wavelength sensitive opsin) for color vision by absorbing light and mediating visual signal transduction. Mutations cause deutanopic colorblindness through an X-linked recessive inheritance pattern. The pathogenic mechanism involves gain-of-function effects, often resulting from unequal recombination events between the tandemly arrayed opsin genes on the X chromosome.

ResearchSummary from RefSeq, UniProt, Mechanism

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]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.36

Clinical Summary— OPN1MW2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

18 VUS of 26 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.36LOEUF

pLI 0.245

Z-score 1.19

OE 0.30 (0.10–1.36)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.35Z-score

OE missense 0.87 (0.69–1.10)

51 obs / 58.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.10–1.36)

0≤0.351.4

Missense OE?0.87 (0.69–1.10)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 1 / 3.3Missense obs/exp: 51 / 58.6Syn Z: 0.03

This gene — mechanism propensity

0.74top 25%

GOF

0.76top 25%

LOF

0.3260th %ile

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

GOFprediction above median

DNprediction 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.

ClinVar Variant Classifications

26 submitted variants in ClinVar

ClinVar

Classification Summary

VUS18

Likely Benign8

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	18	0	18
Likely Benign	5	3	8
Benign	0	0	0
Total	23	3	26

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

65 pathogenic / likely-pathogenic (of 74) ClinVar copy-number / structural variants overlap OPN1MW2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →