OPN1LW

Chr XXLRX-linked

opsin 1, long wave sensitive

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

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLR/X-linkedLOEUF 0.262 OMIM phenotypes
Clinical SummaryOPN1LW
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Gene-Disease Validity (ClinGen)
red color blindness · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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
181 unique Pathogenic / Likely Pathogenic· 45 VUS of 240 total submissions
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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

LoF intolerant — likely haploinsufficient
LoF Constraint
0.26LOEUF
pLI 0.975
Z-score 3.13
OE 0.00 (0.000.26)
Highly constrained

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

Missense Constraint
0.47Z-score
OE missense 0.89 (0.771.03)
126 obs / 141.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.26)
00.351.4
Missense OE0.89 (0.771.03)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 0 / 11.4Missense obs/exp: 126 / 141.6Syn Z: -0.19
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveOPN1LW-related blue cone monochromacyLOFXLR
DN
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.

LOFLOEUF 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

240 submitted variants in ClinVar

Classification Summary

Pathogenic175
Likely Pathogenic6
VUS45
Likely Benign7
Benign4
Conflicting1
175
Pathogenic
6
Likely Pathogenic
45
VUS
7
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
3
168
0
175
Likely Pathogenic
2
0
4
0
6
VUS
0
27
18
0
45
Likely Benign
0
4
1
2
7
Benign
0
2
1
1
4
Conflicting
1
Total6361923238

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

View in ClinVar →

Protein Context — Lollipop Plot

OPN1LW · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC