OPN1LW

Chr XXLRX-linked

opsin 1, long wave sensitive

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

NCBI Gene: 5956 ENSG00000102076 UniProt: P04000

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]

Primary Disease Associations & Inheritance

Blue cone monochromacyMIM #303700

XLR

Colorblindness, protanMIM #303900

X-linked

UniProtColorblindness, partial, protan series

237

ClinVar variants

181

Pathogenic / LP

0.98

pLI score· haploinsufficient

Active trials

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

181 Pathogenic / Likely Pathogenic· 44 VUS of 237 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.47Z-score

OE missense 0.89 (0.77–1.03)

126 obs / 141.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.26)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.77–1.03)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03

0≤1.21.6

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