Affinage

OPN1LW

Long-wave-sensitive opsin 1 · UniProt P04000

Length
364 aa
Mass
40.6 kDa
Annotated
2026-04-29
100 papers in source corpus 4 papers cited in narrative 4 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OPN1LW encodes the long-wavelength-sensitive (red) cone opsin, and specific exon 3 haplotypes (e.g., LVAVA, LIAVA) generated by unequal recombination or intrachromosomal gene conversion between OPN1LW and OPN1MW disrupt an exonic splicing code, causing profound exon 3 skipping during pre-mRNA splicing and leaving cones nearly devoid of functional photopigment (PMID:27339364, PMID:34440353). These splicing-defective haplotypes cause X-linked cone dysfunction disorders including Blue Cone Monochromacy and cone dystrophy, as well as X-linked high myopia (MYP1), with a frameshift mutation (c.617_620dup) in OPN1LW independently identified as causative for high myopia (PMID:26114493, PMID:34440353). The differential photopigment content between adjacent cones expressing skipping versus non-skipping haplotypes generates abnormal contrast signals that are associated with axial elongation and myopia development (PMID:35741704).

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2015 Medium

    Establishing that pathogenic OPN1LW variants—including the LVAVA exon 3 haplotype and a frameshift mutation—are the molecular basis of X-linked high myopia at the MYP1 locus resolved the long-sought genetic identity of this condition.

    Evidence Whole-exome/whole-genome sequencing with Sanger validation and LOD score analysis in myopia families

    PMID:26114493

    Open questions at the time
    • Cosegregation shown in limited families; independent replication in large cohorts not yet reported
    • Mechanism by which opsin defects drive axial elongation was not determined
    • No functional assay of the LVAVA haplotype's effect on splicing was performed in this study
  2. 2016 Medium

    Demonstrating that de novo intrachromosomal gene conversion from OPN1MW to OPN1LW creates pathogenic haplotypes (e.g., LIAVA) that cause exon 3 skipping established the molecular mechanism linking opsin gene rearrangement to Blue Cone Monochromacy.

    Evidence Semi-quantitative minigene splicing assay, long-range PCR and Sanger sequencing with pedigree analysis

    PMID:27339364

    Open questions at the time
    • Minigene assay in heterologous system; splicing behavior not confirmed in cone photoreceptors in vivo
    • Quantitative relationship between residual correctly spliced transcript and photopigment levels not established
    • Frequency of de novo gene conversion events in the germline not determined
  3. 2021 Medium

    Systematic characterization of multiple exon 3 haplotypes unified diverse cone dysfunction phenotypes (Blue Cone Monochromacy, X-linked cone dystrophy) under a single splicing-disruption mechanism driven by unequal recombination between OPN1LW and OPN1MW.

    Evidence Minigene splicing assays across multiple haplotypes combined with molecular genetic analysis

    PMID:34440353

    Open questions at the time
    • No structural or biochemical explanation for why specific amino acid combinations disrupt exonic splicing enhancers
    • In vivo photoreceptor-level confirmation of exon 3 skipping still lacking
    • Genotype–phenotype correlation for intermediate-skipping haplotypes not resolved
  4. 2022 Medium

    Linking exon 3-skipping haplotypes to common refractive error extended the disease relevance of OPN1LW splicing defects beyond rare cone dystrophies to high myopia, proposing that differential photopigment content between adjacent cones generates aberrant contrast signals that drive axial elongation.

    Evidence Long-distance PCR genotyping, association analysis of spherical equivalent refraction with OPN1LW haplotype in males of European ancestry, contrast-reducing spectacle lens trial

    PMID:35741704

    Open questions at the time
    • Association study from a single lab; independent replication in diverse populations not reported
    • Contrast-signal hypothesis for axial elongation remains a model without direct experimental test of the signaling pathway
    • Whether female carriers with mosaic cone expression also show myopia-related phenotype is unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: why specific exon 3 codon combinations disrupt exonic splicing enhancers at the RNA/protein level, whether exon 3 skipping occurs in human cone photoreceptors in vivo, and what retinal signaling pathway converts abnormal inter-cone contrast into axial elongation.
  • No structural or cis-regulatory element mapping explains haplotype-specific splicing disruption
  • No in vivo photoreceptor transcript data confirming exon 3 skipping in patient tissue
  • Downstream signaling cascade linking cone contrast abnormalities to scleral remodeling and axial elongation is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-9709957 Sensory Perception 3 R-HSA-8953854 Metabolism of RNA 2
Partners
OPN1MW

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 Unique haplotypes in OPN1LW (specifically the LVAVA haplotype) are responsible for X-linked high myopia mapped to MYP1; a frameshift mutation (c.617_620dup, p.Phe208Argfs*51) in OPN1LW was also identified as causative, and the haplotype cosegregated with high myopia in families. Whole-exome sequencing, whole-genome sequencing, Sanger sequencing, long-range PCR, LOD score analysis Investigative Ophthalmology & Visual Science Medium 26114493
2016 De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline can create pathogenic haplotypes (e.g., LIAVA) causing Blue Cone Monochromacy; specific exon 3 haplotypes of OPN1LW/OPN1MW cause aberrant pre-mRNA splicing (exon 3 skipping) resulting in loss of functional photopigment and cone dysfunction. Semi-quantitative minigene splicing assay, long-range PCR, Sanger sequencing, pedigree analysis Scientific Reports Medium 27339364
2021 Intermixing of OPN1LW and OPN1MW genes through unequal recombination generates exon 3 haplotypes that disrupt the exonic splicing code, causing profound exon 3 skipping during pre-mRNA splicing; cones expressing skipping haplotypes are nearly devoid of photopigment, resulting in an array of vision disorders including Blue Cone Monochromacy and X-linked cone dystrophy. Minigene splicing assay, molecular genetic analysis of haplotypes, review of functional splicing data Genes Medium 34440353
2022 OPN1LW exon 3 haplotypes that cause profound exon 3 skipping are associated with high myopia; cones expressing skipping haplotypes have abnormally low photopigment content while adjacent cones expressing non-skipping haplotypes have relatively full photopigment, and the resulting abnormal contrast signals between adjacent cones are hypothesized to stimulate axial elongation driving myopia. Long-distance PCR, Sanger sequencing, association analysis of spherical equivalent refraction with OPN1LW haplotype in males of European ancestry, contrast-reducing spectacle lens trial Genes Medium 35741704

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 1793 8413673
2001 p300/CBP proteins: HATs for transcriptional bridges and scaffolds. Journal of cell science 894 11559745
1996 Role of CBP/P300 in nuclear receptor signalling. Nature 823 8779723
1996 An essential role for p300/CBP in the cellular response to hypoxia. Proceedings of the National Academy of Sciences of the United States of America 645 8917528
2017 Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours. Nature 639 28953875
1997 Binding and modulation of p53 by p300/CBP coactivators. Nature 619 9194565
1997 Synergistic activation of transcription by CBP and p53. Nature 530 9194564
2004 p300/CBP and cancer. Oncogene 519 15156177
1997 RNA helicase A mediates association of CBP with RNA polymerase II. Cell 471 9323138
1996 Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha. Nature 428 8848048
2008 Nitric oxide-induced nuclear GAPDH activates p300/CBP and mediates apoptosis. Nature cell biology 345 18552833
1998 Conjunction dysfunction: CBP/p300 in human disease. Trends in genetics : TIG 343 9613201
2017 RNA Binding to CBP Stimulates Histone Acetylation and Transcription. Cell 297 28086087
1999 p300 and CBP: partners for life and death. Journal of cellular physiology 240 10497301
2021 Targeting the p300/CBP Axis in Lethal Prostate Cancer. Cancer discovery 231 33431496
2015 CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. Proceedings of the National Academy of Sciences of the United States of America 214 26261308
2001 p300/CBP/p53 interaction and regulation of the p53 response. European journal of biochemistry 203 11358491
2022 Histone acetyltransferases CBP/p300 in tumorigenesis and CBP/p300 inhibitors as promising novel anticancer agents. Theranostics 192 35836809
1999 CBP-independent activation of CREM and CREB by the LIM-only protein ACT. Nature 190 10086359
2000 CBP/p300 interact with and function as transcriptional coactivators of BRCA1. Proceedings of the National Academy of Sciences of the United States of America 179 10655477
1996 MAP kinase-dependent transcriptional coactivation by Elk-1 and its cofactor CBP. Biochemical and biophysical research communications 169 8941362
1997 The multifunctional role of the co-activator CBP in transcriptional regulation. Recent progress in hormone research 165 9238849
2013 Lysine acetyltransferases CBP and p300 as therapeutic targets in cognitive and neurodegenerative disorders. Current pharmaceutical design 138 23448461
2021 Targeted degradation of the enhancer lysine acetyltransferases CBP and p300. Cell chemical biology 132 33400925
2007 Expression of HDAC1 and CBP/p300 in human colorectal carcinomas. Journal of clinical pathology 124 17720775
2020 Targeting p300/CBP Attenuates Hepatocellular Carcinoma Progression through Epigenetic Regulation of Metabolism. Cancer research 118 33361394
2000 Competitive recruitment of CBP and Rb-HDAC regulates UBF acetylation and ribosomal transcription. Molecular cell 114 11106745
2012 Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration. The Journal of cell biology 109 22270919
2001 Mitogen-regulated RSK2-CBP interaction controls their kinase and acetylase activities. Molecular and cellular biology 106 11564891
2002 The versatile functions of the transcriptional coactivators p300 and CBP and their roles in disease. Histology and histopathology 104 11962765
1996 p300 and CBP as transcriptional regulators and targets of oncogenic events. Biological chemistry 101 8960368
2001 CBP, a transcriptional coactivator and acetyltransferase. Biochemistry and cell biology = Biochimie et biologie cellulaire 98 11467739
2004 Targeting CREB-binding protein (CBP) loss of function as a therapeutic strategy in neurological disorders. Biochemical pharmacology 97 15313413
2004 Loss of CBP causes T cell lymphomagenesis in synergy with p27Kip1 insufficiency. Cancer cell 92 14998493
2005 Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease. The EMBO journal 89 15635450
2023 Therapeutic targeting of EP300/CBP by bromodomain inhibition in hematologic malignancies. Cancer cell 88 37995682
2009 Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling. PLoS biology 88 19924292
2014 Trithorax monomethylates histone H3K4 and interacts directly with CBP to promote H3K27 acetylation and antagonize Polycomb silencing. Development (Cambridge, England) 87 24550119
2012 Genomic occupancy of the transcriptional co-activators p300 and CBP. Transcription 87 23131664
2005 Mutations and deletions of the CBP gene in human lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 80 15701835
2019 Bromodomain inhibition of the coactivators CBP/EP300 facilitate cellular reprogramming. Nature chemical biology 76 30962627
2004 The RCP-Rab11 complex regulates endocytic protein sorting. Molecular biology of the cell 75 15181150
2022 Oxidative stress-CBP axis modulates MOB1 acetylation and activates the Hippo signaling pathway. Nucleic acids research 73 35349706
2016 Regulatory T Cell Modulation by CBP/EP300 Bromodomain Inhibition. The Journal of biological chemistry 69 27056325
2005 Mutant huntingtin represses CBP, but not p300, by binding and protein degradation. Molecular and cellular neurosciences 69 15994095
2001 Functional interaction between coactivators CBP/p300, PCAF, and transcription factor FKLF2. The Journal of biological chemistry 64 11748222
2017 CBP Regulates Recruitment and Release of Promoter-Proximal RNA Polymerase II. Molecular cell 62 29056321
2001 Interactions between CBP, NF-kappaB, and CREB in the lungs after hemorrhage and endotoxemia. American journal of physiology. Lung cellular and molecular physiology 62 11435217
2020 Antitumor activity of the dual BET and CBP/EP300 inhibitor NEO2734. Blood advances 61 32882003
1999 Cooperation of the transcriptional coactivators CBP and p300 with Stat6. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 59 10454341
2020 Differential contribution of p300 and CBP to regulatory element acetylation in mESCs. BMC molecular and cell biology 57 32690000
2016 Salicylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity. eLife 57 27244239
2002 Inhibition of CBP-mediated protein acetylation by the Ets family oncoprotein PU.1. Molecular and cellular biology 57 11997509
2023 Epigenetic mechanisms to propagate histone acetylation by p300/CBP. Nature communications 56 37460559
2018 Modulating the masters: chemical tools to dissect CBP and p300 function. Current opinion in chemical biology 55 30025258
1999 Function for p300 and not CBP in the apoptotic response to DNA damage. Oncogene 52 10523850
2020 Mutant p53 Drives Cancer Metastasis via RCP-Mediated Hsp90α Secretion. Cell reports 51 32640214
1999 Activation of Smad1-mediated transcription by p300/CBP. Biochimica et biophysica acta 50 10673036
2012 CBP and p300 histone acetyltransferases contribute to homologous recombination by transcriptionally activating the BRCA1 and RAD51 genes. PloS one 49 23285190
2020 SATB2 drives glioblastoma growth by recruiting CBP to promote FOXM1 expression in glioma stem cells. EMBO molecular medicine 48 33124191
2016 Development of Selective CBP/P300 Benzoxazepine Bromodomain Inhibitors. Journal of medicinal chemistry 48 27673482
2015 Ku80 cooperates with CBP to promote COX-2 expression and tumor growth. Oncotarget 47 25797267
2015 Unique Variants in OPN1LW Cause Both Syndromic and Nonsyndromic X-Linked High Myopia Mapped to MYP1. Investigative ophthalmology & visual science 47 26114493
2020 CBP mediated DOT1L acetylation confers DOT1L stability and promotes cancer metastasis. Theranostics 44 32042335
2006 Differential role for CBP and p300 CREB-binding domain in motor skill learning. Behavioral neuroscience 44 16768624
2019 Combination Targeting of the Bromodomain and Acetyltransferase Active Site of p300/CBP. Biochemistry 43 30924641
2013 CREB-binding protein (CBP) regulates β-adrenoceptor (β-AR)-mediated apoptosis. Cell death and differentiation 41 23579242
2003 Inhibition of p300/CBP by early B-cell factor. Molecular and cellular biology 41 12748286
2016 Modulation of p300/CBP Acetylation of Nucleosomes by Bromodomain Ligand I-CBP112. Biochemistry 40 27332697
2013 Role of CGRP-receptor component protein (RCP) in CLR/RAMP function. Current protein & peptide science 40 23745704
2023 Discovery of Exceptionally Potent, Selective, and Efficacious PROTAC Degraders of CBP and p300 Proteins. Journal of medicinal chemistry 39 37276143
2021 SIRT6-CBP-dependent nuclear Tau accumulation and its role in protein synthesis. Cell reports 38 33910019
2002 Acetyltransferase machinery conserved in p300/CBP-family proteins. Oncogene 38 11948408
2000 Viral replication and the coactivators p300 and CBP. Trends in microbiology 38 11115752
2018 CoA synthase regulates mitotic fidelity via CBP-mediated acetylation. Nature communications 37 29531224
2020 Zeb1 for RCP-induced oral cancer cell invasion and its suppression by resveratrol. Experimental & molecular medicine 32 32728068
2019 CBP/p300 in brain development and plasticity: disentangling the KAT's cradle. Current opinion in neurobiology 32 30856481
2018 DYRK1A interacts with histone acetyl transferase p300 and CBP and localizes to enhancers. Nucleic acids research 32 30137413
2022 Insight from OPN1LW Gene Haplotypes into the Cause and Prevention of Myopia. Genes 30 35741704
2015 The LIM protein Ajuba promotes adipogenesis by enhancing PPARγ and p300/CBP interaction. Cell death and differentiation 30 26113042
2017 The aPKC-CBP Pathway Regulates Post-stroke Neurovascular Remodeling and Functional Recovery. Stem cell reports 29 29173896
2016 De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy. Scientific reports 29 27339364
2008 CBP/p300-interacting protein CITED1 modulates parathyroid hormone regulation of osteoblastic differentiation. Endocrinology 29 18187554
2019 CBP and SRF co-regulate dendritic growth and synaptic maturation. Cell death and differentiation 28 30850733
1999 The coactivators p300 and CBP have different functions during the differentiation of F9 cells. Journal of molecular medicine (Berlin, Germany) 28 10475063
1997 Prospects of riboflavin carrier protein (RCP) as an antifertility vaccine in male and female mammals. Human reproduction update 27 9459278
2021 Intermixing the OPN1LW and OPN1MW Genes Disrupts the Exonic Splicing Code Causing an Array of Vision Disorders. Genes 26 34440353
2018 RCP induces FAK phosphorylation and ovarian cancer cell invasion with inhibition by curcumin. Experimental & molecular medicine 26 29700289
2016 CBP/p300 acetyltransferases regulate the expression of NKG2D ligands on tumor cells. Oncogene 25 27477692
2009 Spatiotemporal expression of histone acetyltransferases, p300 and CBP, in developing embryonic hearts. Journal of biomedical science 25 19272189
2009 Biochemical characterization of riboflavin carrier protein (RCP) in prostate cancer. Frontiers in bioscience (Landmark edition) 25 19273299
2000 Insight into the tumor suppressor function of CBP through the viral oncoprotein tax. Gene expression 25 11097423
2019 Gene activation by dCas9-CBP and the SAM system differ in target preference. Scientific reports 24 31792240
2009 Interleukin-4 activates androgen receptor through CBP/p300. The Prostate 24 18819102
2021 The impact of CBP expression in estrogen receptor-positive breast cancer. Clinical epigenetics 23 33827682
2019 Rab25 and RCP in cancer progression. Archives of pharmacal research 23 30761451
2024 P300/CBP Regulates HIF-1-Dependent Sympathetic Activation and Hypertension by Intermittent Hypoxia. American journal of respiratory cell and molecular biology 22 37874694
2021 Inhibition of CBP synergizes with the RNA-dependent mechanisms of Azacitidine by limiting protein synthesis. Nature communications 22 34663789
2020 USP12 translocation maintains interferon antiviral efficacy by inhibiting CBP acetyltransferase activity. PLoS pathogens 22 31899788
2015 CBP binding outside of promoters and enhancers in Drosophila melanogaster. Epigenetics & chromatin 22 26604986