PMID: 26114493

Gene: OPN1LW

HGNC: 9936

Disease: protan color blindness

MONDO: 0010565

InheritancePattern: X-linked

Prevalence: The overall prevalence of protan color blindness is approximately 1% in males, which is higher than that of blue cone monochromacy (~1 in 100,000, PMID: 35759666).

Penetrance: Known disease-causing alleles appear to be almost completely penetrant in males (PMID: 21167193).

Case#: Li_2015_Proband_HM429III3, onset before age 7 years, male, seen at a medical center in Guangzhou

CasePresentingHPOs: Abnormal optic disc morphology HP:0012795, Abnormal morphology of the choroidal vasculature HP:0025568, Abnormal light-adapted electroretinogram HP:0008275, Protanopia HP:0011522

CaseHPOFreeText: The proband has a diagnosis of early onset high myopia, yet also shows protanopia. He exhibits myopic fundus changes, with temporal crescent of optic nerve head and tigroid appearance of posterior retina. Rod ERG responses are normal, while cone responses are mildly to moderately reduced.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Genotyping of the proband was performed by whole exome sequencing.

CaseMethod1: whole exome sequencing

CaseMethod2: Sanger sequencing of OPN1LW

CaseGenotypingMethod: Genotyping of the proband was performed by whole exome sequencing, followed by Sanger sequencing of OPN1LW.

Variant: The individual harbors the NM_020061.6(OPN1LW):c.617_620dup (p.Phe208ArgfsTer51) variant in the hemizygous state.

CAID: CA2739290587

gnomAD: The variant was not found in gnomAD version 4.1.0.

VariantEvidence: NM_020061.6(OPN1LW):c.617_620dup (p.Phe208ArgfsTer51) is a nonsense variant in exon 4 of 6 that is predicted to undergo nonsense-mediated decay.

CaseAddInfo: The proband was seen at a medical center in Guangzhou. 4 other male family members are similarly affected but ungenotyped.

CasePMIDs: N/A

Selection B- Gene function is consistent with phenotype.

ExperimentName: OPN1LW encodes a long-wave-sensitive opsin and can rescue cone-mediated function when subretinally injected in Opn1mw−/−/Opn1sw−/− mice.

GOterm: GO:0007602 (phototransduction)

FunctionalEvidence: Subretinal injection of AAV carrying the OPN1LW gene encoding human L-opsin into mice at age 2 months or younger promoted cone outer segment regeneration () and rescued cone functions such as the b-wave amplitude of the long wavelength-mediated electroretinogram response (Figures 2A, 2B, 4D) and visually guided behavior (Figure 4E).

FunctionalHPO: Protanopia HP:0011522

PMID: 35272502

Gene: OPN1LW

HGNC: 9936

Disease: protan color blindness

MONDO: 0010565

InheritancePattern: X-linked

Prevalence: The overall prevalence of protan color blindness is approximately 1% in males, which is higher than that of blue cone monochromacy (~1 in 100,000, PMID: 35759666).

Penetrance: Known disease-causing alleles appear to be almost completely penetrant in males (PMID: 21167193).

Case#: Family_11864_Proband_II-2, onset before age 7 years, male, seen at a medical center in Guangzhou

CasePresentingHPOs: High myopia HP:0011003, Blurred vision HP:0000622, Childhood onset HP:0011463, Protanopia HP:0011522

CaseHPOFreeText: The proband is part of a cohort in which all patients had a diagnosis of early onset high myopia, with onset in early childhood and either high myopia or axial length >25 mm before age 7, or refractive errors <-10 as an adult.

CaseNotHPOs: Nystagmus HP:0000639, Photophobia HP:0000613, Nyctalopia HP:0000662

CaseNotHPOFreeText: N/A

CasePreviousTesting: Genotyping of the proband was performed by either targeted exome sequencing or whole exome sequencing.

CaseMethod1: targeted exome or whole exome sequencing

CaseMethod2: Sanger sequencing of OPN1LW

CaseGenotypingMethod: Genotyping of the proband was performed by either targeted exome sequencing or whole exome sequencing, followed by Sanger sequencing of OPN1LW.

Variant: The individual harbors the NM_020061.6(OPN1LW):c.427_433dup (p.Ala145ValfsTer23) variant in the hemizygous state.

CAID: CA2695237718

gnomAD: The variant was not found in gnomAD version 4.1.0.

VariantEvidence: NM_020061.6(OPN1LW):c.427_433dup (p.Ala145ValfsTer23) is a nonsense variant in exon 3 of 6 that is predicted to undergo nonsense-mediated decay.

CaseAddInfo: The proband was seen at a medical center in Guangzhou. The variant was inherited from the proband's unaffected mother.

CasePMIDs: N/A

Case#: Family_11850_Proband_II-2, onset before age 7 years, male, seen at a medical center in Guangzhou

CasePresentingHPOs: High myopia HP:0011003, Blurred vision HP:0000622, Childhood onset HP:0011463, Protanopia HP:0011522

CaseHPOFreeText: The proband is part of a cohort in which all patients had a diagnosis of early onset high myopia, with onset in early childhood and either high myopia or axial length >25 mm before age 7, or refractive errors <-10 as an adult.

CaseNotHPOs: Nystagmus HP:0000639, Photophobia HP:0000613, Nyctalopia HP:0000662

CaseNotHPOFreeText: N/A

CasePreviousTesting: Genotyping of the proband was performed by either targeted exome sequencing or whole exome sequencing.

CaseMethod1: targeted exome or whole exome sequencing

CaseMethod2: Sanger sequencing of OPN1LW

CaseGenotypingMethod: Genotyping of the proband was performed by either targeted exome sequencing or whole exome sequencing, followed by Sanger sequencing of OPN1LW.

Variant: The individual harbors the NM_020061.6(OPN1LW):c.518_519insC (p.Ala174CysfsTer?) variant in the hemizygous state.

CAID: CA3071606830

gnomAD: The variant was not found in gnomAD version 4.1.0.

VariantEvidence: NM_020061.6(OPN1LW):c.518_519insC (p.Ala174CysfsTer?) is a nonsense variant in exon 3 of 6 that is predicted to undergo nonsense-mediated decay.

CaseAddInfo: The proband was seen at a medical center in Guangzhou. The variant was inherited from the proband's unaffected mother.

CasePMIDs: N/A

Case#: Family_9073_Proband_III-1, onset before age 7 years, male, seen at a medical center in Guangzhou

CasePresentingHPOs: High myopia HP:0011003, Blurred vision HP:0000622, Childhood onset HP:0011463, Protanopia HP:0011522

CaseHPOFreeText: The proband is part of a cohort in which all patients had a diagnosis of early onset high myopia, with onset in early childhood and either high myopia or axial length >25 mm before age 7, or refractive errors <-10 as an adult.

CaseNotHPOs: Nystagmus HP:0000639, Photophobia HP:0000613, Nyctalopia HP:0000662

CaseNotHPOFreeText: N/A

CasePreviousTesting: Genotyping of the proband was performed by either targeted exome sequencing or whole exome sequencing.

CaseMethod1: targeted exome or whole exome sequencing

CaseMethod2: Sanger sequencing of OPN1LW

CaseGenotypingMethod: Genotyping of the proband was performed by either targeted exome sequencing or whole exome sequencing, followed by Sanger sequencing of OPN1LW.

Variant: The individual harbors the NM_020061.6:c.757C>T (p.Gln253Ter) variant in the hemizygous state.

CAID: CA415307744

gnomAD: The variant was not found in gnomAD version 4.1.0.

VariantEvidence: NM_020061.6:c.757C>T (p.Gln253Ter) is a nonsense variant in exon 5 of 6 that is predicted to undergo nonsense-mediated decay.

CaseAddInfo: The proband was seen at a medical center in Guangzhou. A maternal uncle is similarly affected but ungenotyped.

CasePMIDs: N/A

Case#: Family_22142_Proband_II-1, onset before age 7 years, male, seen at a medical center in Guangzhou

CasePresentingHPOs: High myopia HP:0011003, Blurred vision HP:0000622, Childhood onset HP:0011463, Protanopia HP:0011522

CaseHPOFreeText: The proband is part of a cohort in which all patients had a diagnosis of early onset high myopia, with onset in early childhood and either high myopia or axial length >25 mm before age 7, or refractive errors <-10 as an adult.

CaseNotHPOs: Nystagmus HP:0000639, Photophobia HP:0000613, Nyctalopia HP:0000662

CaseNotHPOFreeText: N/A

CasePreviousTesting: Genotyping of the proband was performed by either targeted exome sequencing or whole exome sequencing.

CaseMethod1: targeted exome or whole exome sequencing

CaseMethod2: Sanger sequencing of OPN1LW

CaseGenotypingMethod: Genotyping of the proband was performed by either targeted exome sequencing or whole exome sequencing, followed by Sanger sequencing of OPN1LW.

Variant: The individual harbors the NM_020061.6(OPN1LW):c.739C>T (p.Arg247Ter) variant in the hemizygous state.

ClinVarID: 10503

gnomAD: The variant was not found in gnomAD version 4.1.0.

VariantEvidence: NM_020061.6(OPN1LW):c.739C>T (p.Arg247Ter) is a nonsense variant in exon 3 of 6 that is predicted to undergo nonsense-mediated decay.

CaseAddInfo: The proband was seen at a medical center in Guangzhou. The variant was inherited from the proband's unaffected mother.

CasePMIDs: N/A

PMID: 34287097

Gene: OPN1LW

HGNC: 9936

Disease: red color blindness

MONDO: MONDO:0010565

InheritancePattern: X-linked

Prevalence: Protanomaly and protanopia are common disorders with peak frequencies (among the males of certain populations) of 1.94% and 1.28%, respectively (PMID: 30258865).

Penetrance: The penetrance of the phenotype among hemizygous cases appears to be complete or near-complete.

Case#: Holmquist_2021_Proband, onset before age 6 years, male, family national origin from Sweden

CasePresentingHPOs: Abnormal optic disc morphology HP:0012795, Abnormal morphology of the choroidal vasculature HP:0025568, Abnormal light-adapted electroretinogram HP:0008275, Protanopia HP:0011522

CaseHPOFreeText: The proband has a diagnosis of early onset high myopia, yet also shows protanopia. He exhibits myopic fundus changes, with temporal crescent of optic nerve head and tigroid appearance of posterior retina. Rod ERG responses are normal, while cone responses are mildly to moderately reduced.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Genotyping of the proband was performed by PCR / RFLP-based analysis of OPN1LW and OPN1MW locus structure, real-time PCR-based analysis of OPN1LW and OPN1MW copy number, and Sanger sequencing of long-range PCR products from exon 3 of OPN1LW and OPN1MW.

CaseMethod1: RFLP- and RT-PCR-based analyses of OPN1LW and OPN1MW structure and copy number

CaseMethod2: long-range PCR and Sanger sequencing of OPN1LW and OPN1MW

CaseGenotypingMethod: Genotyping of the proband was performed by RFLP- and RT-PCR-based analyses of OPN1LW and OPN1MW structure and copy number, followed by long-range PCR and Sanger sequencing of OPN1LW and OPN1MW.

Variant: The individual harbors the NM_020061.6(OPN1LW):c.511_513delinsATT (p.Val171Ile) and NM_020061.6(OPN1LW):c.532A>G (p.Ile178Val) variants in the hemizygous state.

ClinVarID / CAID: CA2695237719 / 403267

gnomAD: The NM_020061.6(OPN1LW):c.511_513delinsATT (p.Val171Ile) variant was not found in gnomAD v4.1.0. The NM_020061.6(OPN1LW):c.532A>G (p.Ile178Val) variant is found in gnomAD v4.1.0 at a frequency of 0.04886 in the African / African American population, with 862 total homozygotes.

VariantEvidence: NM_020061.6(OPN1LW):c.511_513delinsATT (p.Val171Ile) and NM_020061.6(OPN1LW):c.532A>G (p.Ile178Val) are missense variants in exon 3 that make up the "LIAVA" genotype that has been previously reported in the context of this disease (PMID: 22732407) but individually are not known to be disease-causing.

CaseAddInfo: The proband has a similarly affected brother who shares the same genotype, and an unaffected brother who does not harbor the variants.

CasePMIDs: PMID: 27339364

ExperimentName: Colorblind squirrel monkeys were rescued by human OPN1LW.

NonHumanModel: Saimiri sciureus

GeneAlteration: Male squirrel monkeys were missing OPN1LW gene. Controls with the intact gene were not part of the study.

RescueVariant: Rescue was performed by subretinal injection of recombinant adeno-associated virus containing human OPN1LW under control of the appropriate enhancer and promoter and featured the wild-type gene rather than a variant.

RescuePhenotype: The rescued phenotypes are inability to discriminate between blue and green wavelengths to obtain a food reward and defects in performance on a computer-administered Cambridge colour test.

RescueMethod: This rescue model has injection of recombinant adeno-associated virus containing human wild-type OPN1LW under control of the appropriate enhancer and promoter.

RescueEvidence: Squirrel monkeys gained the ability to discriminate between blue and green wavelengths to obtain a food reward (data not shown), as well as significant improvement in ability to distinguish colors occurring at ~20 weeks post-injection (Figure 3A). Gaps in the ability to detect certain wavelengths pre-injection (solid lines) were filled in post-injection (dotted lines) in monkey 1 (Panel 3B) and monkey 2 (Panel 3C). These confirmed that monkeys had become trichomatic and matched the new ability to access food rewards.

ModelVariant: The model does not include any human OPN1LW variant, only the wild-type gene.

PMID: 19759534

Gene: OPN1LW

HGNC: 9936

Disease: protan color blindness

MONDO: 0010565

InheritancePattern: X-linked

Prevalence: The overall prevalence of protan color blindness is approximately 1% in males, which is higher than that of blue cone monochromacy (~1 in 100,000, PMID: 35759666).

Penetrance: Known disease-causing alleles appear to be almost completely penetrant in males (PMID: 21167193).

PMID: 15148406

Gene: OPN1LW

HGNC: 9936

Disease: protan color blindness

MONDO: 0010565

InheritancePattern: X-linked

Prevalence: The overall prevalence of protan color blindness is approximately 1% in males, which is higher than that of blue cone monochromacy (~1 in 100,000, PMID: 35759666).

Penetrance: Known disease-causing alleles appear to be almost completely penetrant in males (PMID: 21167193).

MM is a patient with replacement of the entire OPN1LW locus by an additional copy of OPN1MW. This proband cannot be scored due to the variant type, but might be used for Functional Alteration in Patient Cells?

ExperimentName: OPN1LW rescue of mice with Opn1mw and Opn1sw defects

RescueModel: Mus musculus

GeneAlteration: Rescue was performed by replacing the endogenous Opn1mw gene with a known benign OPN1LW LIAIS compound variant from unaffected humans, which serves as a wild-type OPN1LW control.

RescueVariant: Rescue was performed by replacing the endogenous Opn1mw gene with a known benign OPN1LW LIAIS compound variant from unaffected humans, which serves as a wild-type OPN1LW control.

RescuePhenotype: The rescued phenotypes are cone outer segment length and number.

RescueMethod: This rescue model has replacement of the mouse Opn1mw gene with a normal variant of human OPN1LW.

RescueEvidence: Replacement of the mouse Opn1mw gene with a normal variant of human OPN1LW results in a shift in sensitivity to detect red wavelengths (Figure 5) and rescues a defect in outer segment length caused by knockout of both Opn1mw and Opn1sw (Figure 13).

ModelVariant: The model harbors homozygous deletion of Opn1sw and either intact Opn1mw or replacement of Opn1mw with human OPN1LW.

PMID: 24801621

Gene: OPN1LW

HGNC: 9936

Disease: protan color blindness

MONDO: 0010565

InheritancePattern: X-linked

Prevalence: The overall prevalence of protan color blindness is approximately 1% in males, which is higher than that of blue cone monochromacy (~1 in 100,000, PMID: 35759666).

Penetrance: Known disease-causing alleles appear to be almost completely penetrant in males (PMID: 21167193).

PMID: 34547123

Gene: OPN1LW

HGNC: 9936

Disease: protan color blindness

MONDO: 0010565

InheritancePattern: X-linked

Prevalence: The overall prevalence of protan color blindness is approximately 1% in males, which is higher than that of blue cone monochromacy (~1 in 100,000, PMID: 35759666).

Penetrance: Known disease-causing alleles appear to be almost completely penetrant in males (PMID: 21167193).

PMID: 40227176

Gene: OPN1LW

HGNC: 9936

Disease: protan color blindness

MONDO: 0010565

InheritancePattern: X-linked

Prevalence: The overall prevalence of protan color blindness is approximately 1% in males, which is higher than that of blue cone monochromacy (~1 in 100,000, PMID: 35759666).

Penetrance: Known disease-causing alleles appear to be almost completely penetrant in males (PMID: 21167193).

Case#: Li_2025_Proband_XXXVII, age 8 years at time of report, male, seen at a medical center in Beijing

CasePresentingHPOs: Abnormal morphology of the choroidal vasculature HP:0025568, High myopia HP:0011003, Best corrected visual acuity 0.1 LogMAR HP:0030554

CaseHPOFreeText: The choroidal vascular abnormality referred to in the text was described as a tesselated fundus. The patient's refractive error was reported as -14.00 and -12.88 in the two eyes, with, axial lengths of 27.01 and 26.64.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Genotyping of the proband was performed by whole genome sequencing.

CaseMethod1: whole genome sequencing

CaseMethod2: possibly Sanger sequencing of OPN1LW

CaseGenotypingMethod: Genotyping of the proband was performed by whole genome sequencing, possibly followed by Sanger sequencing of OPN1LW.

Variant: The individual harbors the NM_020061.6(OPN1LW):c.843G>A (p.Trp281Ter) variant in the hemizygous state.

CAID: CA415308527

gnomAD: The variant is found in gnomAD version 4.1.0 at a frequency of 0.00002111 (1 / 47,376) in the Remaining population. https://gnomad.broadinstitute.org/variant/chrX-154156392-G-A?dataset=gnomad_r4

VariantEvidence: NM_020061.6(OPN1LW):c.843G>A (p.Trp281Ter) is a nonsense variant in exon 5 of 6 that is predicted to undergo nonsense-mediated decay.

CaseAddInfo: The proband was seen at a medical center in Beijing.

CasePMIDs: N/A

ExperimentName: OPN1LW variants identified in myopic patients were expressed exogenously in HEK293T cells and exhibited reduced expression at the mRNA level.

NonPatientCell: HEK293T cells (EFO:0001184)

GeneFunction: GO:0007602 (phototransduction)

GeneAlteration: Site-directed mutagenesis was used to introduce the variants into minigenes encoding portions of the wlid-type OPN1LW gene.

FunctionalEvidence: Three OPN1LW variants identified in myopic patients were expressed exogenously in HEK293T cells and two out of three exhibited reduced expression at the mRNA level (Figures 1A and 1B).

FAVariants: NM_020061.6(OPN1LW):c.973A>G (p.Met325Val), CA415309107, NM_020061.6(OPN1LW):c.970T>A (p.Phe324Ile), CA415309100, NM_020061.6(OPN1LW):c.971T>A (p.Phe324Tyr), CA415309101