OPN1LW

Chr XXLRX-linked

opsin 1, long wave sensitive

Also known as: CBBM, CBP, COD5, RCP, ROP

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

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismXLR/X-linkedLOEUF 0.262 OMIM phenotypes

Clinical Summary— OPN1LW

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Gene-Disease Validity (ClinGen)

red color blindness · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

11 unique Pathogenic / Likely Pathogenic· 27 VUS of 51 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — OPN1LW

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveOPN1LW-related blue cone monochromacyLOFXLR

This gene — mechanism propensity

0.5477th %ile

GOF

0.6640th %ile

LOF

0.56top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF55% of P/LP variants are LoF · LOEUF 0.26

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

51 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9

Likely Pathogenic2

VUS27

Likely Benign7

Benign4

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	3	2	0	9
Likely Pathogenic	2	0	0	0	2
VUS	0	27	0	0	27
Likely Benign	0	4	1	2	7
Benign	0	2	1	1	4
Total	6	36	4	3	49

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

View in ClinVar →

175 pathogenic / likely-pathogenic (of 195) ClinVar copy-number / structural variants overlap OPN1LW — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →