Affinage

OPN1MW

Medium-wave-sensitive opsin 1 · UniProt P04001

Round 2 corrected
Length
364 aa
Mass
40.6 kDa
Annotated
2026-04-29
130 papers in source corpus 20 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OPN1MW encodes the medium-wave-sensitive (green) cone opsin, a G protein-coupled receptor that initiates phototransduction in M-cones with an absorption maximum near 530 nm, underpinning trichromatic color vision (PMID:6140680, PMID:2937147). The spectral difference between OPN1MW and the red opsin OPN1LW is determined by seven amino acid residues (positions 116, 180, 230, 233, 277, 285, 309), and OPN1MW is distinguished biophysically by regeneration through an unprotonated Schiff base intermediate, faster Meta II decay, and weak dimerization propensity (PMID:8185948, PMID:26387074, PMID:28045251, PMID:9494086). Light-activated OPN1MW is phosphorylated by GRK1 and subsequently bound by cone arrestin to terminate signaling, is chaperoned by the RanBP2 cyclophilin domain for proper folding, and carries a conserved O-glycosylation at an N-terminal Ser/Thr domain (PMID:12853434, PMID:8857542, PMID:30948514). Pathogenic exon 3 haplotypes (e.g., LIAVA/LVAVA) cause exon-skipping and Blue Cone Monochromacy, while missense mutations such as W177R cause ER retention and progressive cone dystrophy; AAV-mediated opsin gene delivery rescues cone structure and function in M-opsin knockout mouse models (PMID:34440353, PMID:20579627, PMID:29386880).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1983 High

    Before the gene was cloned, the spectral identity of the M-cone pigment was established by directly measuring an ~530 nm absorption maximum in human foveal cone outer segments, defining the physical property that OPN1MW must encode.

    Evidence Microspectrophotometry of isolated human cone photoreceptors

    PMID:6140680

    Open questions at the time
    • Bimodal sub-population (527.8 vs 533.7 nm) not fully explained
    • Molecular basis of spectral tuning unknown at this stage
  2. 1986 High

    Cloning OPN1MW from Xq28 revealed its tandem arrangement with OPN1LW and 96% amino acid identity, establishing the molecular genetic basis of green–red color discrimination and explaining the high frequency of recombination-driven color vision defects.

    Evidence Genomic/cDNA cloning and sequencing, Southern blotting

    PMID:2937147

    Open questions at the time
    • Which specific residues drive spectral tuning not yet identified
    • Expression regulation within the tandem array unknown
  3. 1989 High

    Characterization of a naturally occurring OPN1LW–OPN1MW fusion gene showed that hybrid gene structure directly determines pigment spectral properties, providing the first genotype-to-phenotype link for color vision variation.

    Evidence DNA sequencing of fusion gene combined with pigment spectroscopy

    PMID:2574415

    Open questions at the time
    • Individual spectral-tuning residues not resolved
  4. 1992 Medium

    Identification of the C203R missense mutation as a cause of severe deuteranomaly established that a single residue change in OPN1MW is sufficient to abolish green cone function, implicating a conserved disulfide bond in protein folding.

    Evidence DNA sequencing with clinical color vision phenotyping in affected individuals

    PMID:1302020

    Open questions at the time
    • No in vitro expression or spectroscopic confirmation of C203R at this stage
    • Mechanism of folding defect inferred from conservation rather than demonstrated
  5. 1994 High

    Systematic mutagenesis resolved the spectral tuning code to exactly seven amino acid positions, answering a decade-long question about which residues account for the 31 nm red–green shift and enabling prediction of hybrid gene phenotypes.

    Evidence 28 chimeric and 30 point-mutant opsins expressed and characterized by UV-Vis spectroscopy

    PMID:8185948

    Open questions at the time
    • Structural mechanism by which each residue shifts absorption not determined
    • In vivo validation of all positions not performed
  6. 1996 High

    Discovery that the RanBP2 cyclophilin domain acts as a specific molecular chaperone for L/M opsins revealed a post-translational folding requirement unique to cone pigments and explained why mutations disrupting folding are particularly pathogenic.

    Evidence Biochemical binding assays and domain dissection across Drosophila and vertebrate systems

    PMID:8857542

    Open questions at the time
    • Whether RanBP2 chaperoning involves proline isomerization in vivo unresolved
    • Stoichiometry and kinetics of the chaperone interaction unknown
  7. 1998 High

    Purification and functional reconstitution of recombinant OPN1MW demonstrated that it activates transducin at roughly half the rate of rhodopsin and exhibits distinct photo-intermediate kinetics (pH-independent Meta I–Meta II equilibrium, faster Meta II decay), establishing core differences between cone and rod signaling.

    Evidence Baculovirus expression in Sf9 cells, affinity purification, UV-Vis spectroscopy, GTPγS-based transducin activation assay

    PMID:9494086

    Open questions at the time
    • Lipid-dependence of photo-intermediate kinetics not fully characterized
    • Comparison to OPN1LW under identical conditions not reported
  8. 1999 High

    Position-dependent expression within the tandem array was demonstrated: only the first or second gene copy is transcribed, explaining why the same hybrid gene causes deuteranomaly in one array position but is phenotypically silent in more distal positions.

    Evidence Long-range PCR with mRNA expression analysis in post-mortem human retinae

    PMID:10319869

    Open questions at the time
    • Locus control region mechanism not fully elucidated
    • Whether position-dependence is absolute or probabilistic unclear
  9. 2002 High

    Functional expression of disease-associated missense mutants (Asn94Lys in OPN1MW; Arg330Gln, Gly338Glu in OPN1LW) demonstrated that color vision deficiency can arise from complete loss of chromophore binding due to misfolding, not only from spectral shifts.

    Evidence Expression in COS-7 cells, reconstitution with 11-cis-retinal, UV-Vis spectrophotometry

    PMID:12051694

    Open questions at the time
    • Folding intermediate trapped by each mutation not characterized
    • Whether pharmacological rescue is possible not tested
  10. 2003 High

    Demonstration that GRK1 phosphorylates light-activated M-cone opsin and that cone arrestin binds the phosphorylated pigment established the canonical desensitization pathway for M-cones, paralleling but distinct from the rod cascade.

    Evidence In situ phosphorylation, isoelectric focusing, immunoprecipitation in Nrl−/−Grk1−/− double-knockout mice

    PMID:12853434

    Open questions at the time
    • Exact phosphorylation sites on OPN1MW not mapped
    • Whether GRK7 contributes in human cones not addressed
  11. 2009 High

    11-cis-retinol was shown to act as an inverse agonist of OPN1MW, suppressing constitutive transducin activation and promoting chromophore binding in cones, revealing a retinoid-handling mechanism absent in rods.

    Evidence Cell-free GTPγS incorporation assay with expressed green opsin, microspectrophotometry of salamander cones

    PMID:19386593

    Open questions at the time
    • Physiological relevance of inverse agonism in intact human cones not demonstrated
    • Source and trafficking of 11-cis-retinol in the cone-Müller cell cycle not resolved
  12. 2010 High

    The W177R mutation was shown to cause ER retention and misfolding-driven cone dystrophy that is refractory to 9-cis-retinal pharmacological chaperone rescue, distinguishing this pathogenic mechanism from the rescuable P23H rhodopsin mutation and highlighting the severity of M-opsin folding mutations.

    Evidence Cell-based expression with ER localization and pharmacological chaperone rescue assays

    PMID:20579627

    Open questions at the time
    • Structural basis for why W177R is unrescuable not determined
    • Whether other chaperone strategies could rescue W177R untested
  13. 2015 Medium

    Discovery that OPN1MW regenerates via an unprotonated Schiff base intermediate, unlike OPN1LW which uses a protonated intermediate, identified a fundamental mechanistic difference between the two highly similar cone pigments and implicated specific structural divergences in the photoactivated state.

    Evidence UV-Vis and fluorescence spectroscopy, site-directed mutagenesis, molecular modeling

    PMID:26387074

    Open questions at the time
    • Single-lab observation not yet independently confirmed
    • Crystal or cryo-EM structure of the intermediate not available
  14. 2016 High

    Biophysical measurement showed OPN1MW has weak dimerization propensity compared to OPN1LW, and the dimerization interface residues (I230, A233, M236 in TM5) overlap with spectral-tuning sites, linking oligomerization state to spectral identity.

    Evidence Time-resolved fluorescence measuring dimerization affinity, site-directed mutagenesis

    PMID:28045251

    Open questions at the time
    • In vivo oligomeric state in cone outer segments not known
    • Functional consequence of differing dimerization propensity on phototransduction not tested
  15. 2016 High

    Functional splicing assays established that specific exon 3 haplotypes (LIAVA, LVAVA) in OPN1MW cause exon 3 skipping, and pedigree analysis demonstrated that intrachromosomal gene conversion generates these pathogenic haplotypes de novo, providing a molecular mechanism for recurrent Blue Cone Monochromacy.

    Evidence Semi-quantitative minigene splicing assay, molecular haplotyping, pedigree analysis

    PMID:27339364 PMID:34440353

    Open questions at the time
    • Splicing regulatory elements mediating exon 3 skipping not identified
    • Frequency of de novo gene conversion events in population not quantified
  16. 2018 High

    AAV5-mediated delivery of human M- or L-opsin into M-opsin knockout mice rescued cone outer segment regrowth and ERG function for at least 13 months, providing the first proof-of-concept for gene therapy of Blue Cone Monochromacy.

    Evidence Subretinal AAV5 injection, ERG, immunohistochemistry, western blotting in Opn1mw−/− mice

    PMID:29386880

    Open questions at the time
    • Optimal therapeutic window not defined
    • Translation to primate retina not yet demonstrated
  17. 2019 High

    O-glycosylation at a conserved N-terminal Ser/Thr domain was identified on human L/M opsins, revealing a previously unrecognized post-translational modification conserved across vertebrates whose functional role remains unknown.

    Evidence Monoclonal antibody recognition, O-glycosidase treatment, jacalin lectin binding, mass spectrometry on native human retina

    PMID:30948514

    Open questions at the time
    • Functional role of O-glycosylation in opsin trafficking or stability not determined
    • Glycosyltransferase responsible not identified
  18. 2022 High

    A critical therapeutic window was defined: AAV-mediated opsin gene therapy rescues M-cone structure and function only when delivered by 2 months in Opn1mw−/− mice, with efficacy declining sharply thereafter, indicating that cone degeneration becomes irreversible and is not driven by proteasomal stress.

    Evidence Subretinal AAV injection at multiple ages, ERG, immunohistochemistry, proteasomal reporter mouse cross

    PMID:35272502

    Open questions at the time
    • Mechanism of irreversible cone loss beyond the window not identified
    • Whether human cones have a comparably narrow window unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structure of OPN1MW (and its photo-intermediates), the functional significance of O-glycosylation and differential dimerization, the identity of splicing regulatory elements governing exon 3 inclusion, and the translational therapeutic window for gene therapy in human Blue Cone Monochromacy patients.
  • No crystal or cryo-EM structure of OPN1MW
  • O-glycosylation function uncharacterized
  • Therapeutic window in primate/human retina undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-9709957 Sensory Perception 5 R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3
Partners
ARR3GNAT2GRK1OPN1LWRANBP2

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 OPN1MW (green cone opsin) gene was isolated and sequenced from the human X chromosome (Xq28), revealing it is arranged in a head-to-tail tandem array with the red opsin gene. The deduced amino acid sequence shows 96% identity with red opsin and 43% identity with blue opsin, establishing the molecular basis of human trichromatic color vision. Genomic and cDNA cloning, DNA sequencing, Southern blotting Science High 2937147
1983 The green cone photoreceptor (M-cone) visual pigment was characterized by microspectrophotometry, establishing an absorption maximum of approximately 530.8 nm (with evidence for a bimodal sub-population distribution at ~533.7 and ~527.8 nm) in human foveal and parafoveal retina. Microspectrophotometry of human cone outer segments Proceedings of the Royal Society of London. Series B High 6140680
1989 A fusion gene derived from recombination between OPN1LW and OPN1MW was sequenced and its encoded photopigment characterized spectroscopically; the pigment encoded by this hybrid gene absorbed light similar to normal M-cone (green) pigment (~530 nm) despite containing coding sequence from both genes, directly linking gene structure to pigment spectral properties. DNA sequencing of fusion gene, pigment spectroscopy Nature High 2574415
1994 The spectral difference (31 nm) between human red (OPN1LW) and green (OPN1MW) cone opsins is determined by exactly 7 amino acid residues (positions 116, 180, 230, 233, 277, 285, and 309), identified through an extensive mutagenesis study of 28 chimeric proteins and 30 point mutants. Replacing these residues converts red-to-green pigment spectral properties. Site-directed mutagenesis, expression of chimeric and point-mutant opsins, spectroscopic characterization Neuron High 8185948
1996 RanBP2, a large cyclophilin-related protein (containing Ran-binding domain 4 [RBD4] and cyclophilin domains), acts as a molecular chaperone specifically for red/green (L/M) opsin in cone photoreceptors. The cyclophilin domain augments and stabilizes the interaction between red/green opsin and RBD4, possibly via proline isomerization, but does not bind opsin directly. Biochemical binding assays, domain dissection, functional chaperone assays in Drosophila/vertebrate systems Nature High 8857542
1998 The human green cone pigment (OPN1MW) was functionally expressed in large-scale Sf9 insect cell cultures using recombinant baculovirus and purified via immobilized metal affinity chromatography. The purified pigment activated rod G-protein transducin at about half the rate of rhodopsin. Photo-intermediate analysis (Meta I, Meta II, Meta III) revealed the Meta I–Meta II equilibrium lacks pH dependence (unlike rod pigment), and the rate of Meta II decay was significantly faster than in rhodopsin. Recombinant expression in Sf9 cells, immobilized metal affinity chromatography purification, UV-Vis spectroscopy, G-protein activation assay, lipid reconstitution The Biochemical Journal High 9494086
1999 The position of a green-red hybrid gene within the OPN1LW/OPN1MW tandem array determines color vision phenotype: the hybrid gene causes deuteranomaly only when it occupies the second position (where it is expressed), and does not cause color vision defects when it is in the third or more distal position (where it is not expressed). mRNA expression analysis confirmed position-dependent expression. Long-range PCR, gene sequencing, mRNA expression analysis in post-mortem retinae Nature Genetics High 10319869
2003 GRK1 (G protein-coupled receptor kinase 1) phosphorylates light-activated M-cone opsin (OPN1MW) at multiple sites in a light-dependent manner in mouse retina. Following phosphorylation, cone arrestin (mCAR) binds to the phosphorylated, light-activated M-cone opsin, quenching phototransduction. In Nrl−/−Grk1−/− double-knockout mice, cone opsins are neither phosphorylated nor bound by cone arrestin. In situ phosphorylation, isoelectric focusing, immunoprecipitation with cone opsin and cone arrestin antibodies, genetic knockout mouse models The Journal of Neuroscience High 12853434
2009 11-cis-retinol acts as an inverse agonist on expressed human green cone opsin (OPN1MW), inactivating its constitutive activity (measured as transducin activation). It also promotes pigment formation (chromophore binding) in salamander cone photoreceptors, supporting a distinct retinoid handling mechanism in cones compared to rods. Cell-free transducin activation assay (GTPγS incorporation), microspectrophotometry of isolated photoreceptors, comparative pharmacology The Journal of Biological Chemistry High 19386593
2002 Three novel missense mutations in OPN1MW (Asn94Lys) and OPN1LW (Arg330Gln, Gly338Glu) cause red/green color vision deficiencies by disrupting visual pigment formation: Asn94Lys and Gly338Glu mutations abolish all detectable absorbance (loss of pigment), while Arg330Gln yields a low-absorbance pigment with λmax of 530 nm, indicating these mutations impair protein folding required for chromophore binding. Mutation identification by DNA sequencing, expression of mutant opsins in COS-7 cells, reconstitution with 11-cis-retinal, UV-Vis spectrophotometry Biochemical and Biophysical Research Communications High 12051694
1992 A missense mutation in OPN1MW (C203R, cysteine to arginine at position 203) causes severe deuteranomaly (green color vision deficiency). This conserved cysteine is necessary for normal green opsin function, presumably for correct protein folding. DNA sequencing, clinical color vision phenotyping Nature Genetics Medium 1302020
2010 The W177R missense mutation affecting OPN1MW (arising by gene conversion making both opsin genes identical to the MW sequence) causes protein misfolding and retention in the endoplasmic reticulum, leading to X-linked cone dystrophy. Unlike the P23H rod opsin mutation, W177R misfolding is not rescued by pharmacological chaperone 9-cis-retinal. Molecular genetic analysis, cell-based expression with ER localization assay, pharmacological chaperone treatment assay American Journal of Human Genetics High 20579627
2015 Human green cone opsin (OPN1MW) and red cone opsin (OPN1LW) adopt different transient conformations during chromophore regeneration: photoactivated green cone opsin regenerates via an unprotonated Schiff base intermediate, whereas red cone opsin forms a typical protonated Schiff base. Site-directed mutagenesis and molecular modeling identified structural differences in the photoactivated state between the two pigments. UV-Vis and fluorescence spectroscopy, site-directed mutagenesis, molecular modeling Cellular and Molecular Life Sciences Medium 26387074
2016 Human red cone opsin (OPN1LW) exhibits a strong propensity for dimerization via a specific interface in the fifth transmembrane helix involving residues I230, A233, and M236, identified by mutagenesis. Green cone opsin (OPN1MW) does not dimerize strongly. Notably, the same residues (I230, A233) responsible for red opsin dimerization are also partially responsible for spectral tuning differences between red and green opsins. Time-resolved fluorescence (measuring dimerization affinity), site-directed mutagenesis, spectroscopic analysis Biochemistry High 28045251
2019 Human red and green cone opsins (OPN1LW and OPN1MW) are O-glycosylated at a conserved N-terminal Ser/Thr-rich domain (at Ser22 in bovine OPSR) in addition to N-glycosylation at Asn34. This O-glycosylation is conserved across vertebrates (mammals, birds, amphibians), as demonstrated by jacalin lectin binding, O-glycosidase treatment revealing the underlying epitope, and mass spectrometry identifying O-glycan on Ser22. Monoclonal antibody recognition assay, O-glycosidase treatment, jacalin lectin binding, mass spectrometry, cross-species analysis The Journal of Biological Chemistry High 30948514
2021 Specific exon 3 haplotypes of OPN1MW (e.g., 'LIAVA', 'LVAVA') cause exon 3 skipping during pre-mRNA splicing, abolishing or severely reducing correctly spliced transcripts, leading to vision disorders including Blue Cone Monochromacy. Intrachromosomal gene conversion between OPN1LW and OPN1MW in the male germline was demonstrated to generate pathogenic haplotypes de novo (e.g., 'LIAVA' from ancestral 'LIAVS'). Semi-quantitative minigene splicing assay, molecular haplotyping, pedigree analysis demonstrating de novo gene conversion Genes High 27339364 34440353
2018 AAV5-mediated subretinal delivery of human OPN1MW or OPN1LW into Opn1mw−/− mice (M-opsin knockout model of Blue Cone Monochromacy) promotes regrowth of cone outer segments in the dorsal retina and rescues M-cone-mediated ERG function. Both M- and L-opsin constructs are effective, and rescue is maintained for at least 13 months post-injection. Subretinal AAV5 gene delivery, electroretinography (ERG), immunohistochemistry, western blotting Molecular Vision High 29386880
2019 AAV5-mediated L-opsin gene therapy can rescue M-cone function and outer segment structure in aged Opn1mw−/− mice (up to 15 months old), demonstrating that the remaining viable cones retain the capacity to respond to opsin gene delivery even at advanced age, though cone outer segment degeneration begins early and ventral S-opsin-dominant cones remain normal. Subretinal AAV5 injection, electroretinography, PNA staining for cone quantification, immunohistochemistry Investigative Ophthalmology & Visual Science High 31469404
2022 Gene augmentation therapy with AAV-mediated human L-opsin delivery rescues cone outer segment structure and function in Opn1mw−/− mice (lacking both M- and S-opsin, a more stringent BCM model), but only when delivered at 2 months of age or younger; therapeutic efficacy is significantly reduced at 5–7 months. Impaired proteasomal activity was excluded as a contributing stress factor in cone degeneration. Subretinal AAV injection, ERG, immunohistochemistry, crossing with proteasomal reporter mouse (UbG76V-GFP) Human Gene Therapy High 35272502

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1986 Molecular genetics of human color vision: the genes encoding blue, green, and red pigments. Science (New York, N.Y.) 1221 2937147
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2015 Cannabidiol (CBD) and its analogs: a review of their effects on inflammation. Bioorganic & medicinal chemistry 397 25703248
1994 Molecular determinants of human red/green color discrimination. Neuron 325 8185948
2005 GCP-WD is a gamma-tubulin targeting factor required for centrosomal and chromatin-mediated microtubule nucleation. Nature cell biology 269 16378099
2015 Fatty acid-binding proteins (FABPs) are intracellular carriers for Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). The Journal of biological chemistry 251 25666611
1983 Human visual pigments: microspectrophotometric results from the eyes of seven persons. Proceedings of the Royal Society of London. Series B, Biological sciences 248 6140680
1986 Molecular biology of the visual pigments. Vision research 237 3303660
1995 Rod photoreceptor neurite sprouting in retinitis pigmentosa. The Journal of neuroscience : the official journal of the Society for Neuroscience 197 7643192
2022 A narrative review of molecular mechanism and therapeutic effect of cannabidiol (CBD). Basic & clinical pharmacology & toxicology 193 35083862
2020 Diversity of molecular targets and signaling pathways for CBD. Pharmacology research & perspectives 187 33169541
1996 Cyclophilin-related protein RanBP2 acts as chaperone for red/green opsin. Nature 186 8857542
2006 Murine CXCR1 is a functional receptor for GCP-2/CXCL6 and interleukin-8/CXCL8. The Journal of biological chemistry 175 17197447
2020 The proposed mechanisms of action of CBD in epilepsy. Epileptic disorders : international epilepsy journal with videotape 152 32053110
2005 GCP-2/CXCL6 synergizes with other endothelial cell-derived chemokines in neutrophil mobilization and is associated with angiogenesis in gastrointestinal tumors. Experimental cell research 141 15652347
2018 Cannabidiol (CBD) Is a Novel Inhibitor for Exosome and Microvesicle (EMV) Release in Cancer. Frontiers in pharmacology 117 30150937
2003 Pharmacological modulation of interleukin-17-induced GCP-2-, GRO-alpha- and interleukin-8 release in human bronchial epithelial cells. European journal of pharmacology 116 12591113
2021 A new Cannabis genome assembly associates elevated cannabidiol (CBD) with hemp introgressed into marijuana. The New phytologist 107 33521943
2003 GRK1-dependent phosphorylation of S and M opsins and their binding to cone arrestin during cone phototransduction in the mouse retina. The Journal of neuroscience : the official journal of the Society for Neuroscience 103 12853434
2003 The CXC chemokine GCP-2/CXCL6 is predominantly induced in mesenchymal cells by interleukin-1beta and is down-regulated by interferon-gamma: comparison with interleukin-8/CXCL8. Laboratory investigation; a journal of technical methods and pathology 85 12533683
2018 The Cannabinoids Δ8THC, CBD, and HU-308 Act via Distinct Receptors to Reduce Corneal Pain and Inflammation. Cannabis and cannabinoid research 83 29450258
2012 The effect of cone opsin mutations on retinal structure and the integrity of the photoreceptor mosaic. Investigative ophthalmology & visual science 80 23139274
2019 CBD loaded microparticles as a potential formulation to improve paclitaxel and doxorubicin-based chemotherapy in breast cancer. International journal of pharmaceutics 77 31811927
2009 Fulfilling the promise of personalized medicine? Systematic review and field synopsis of pharmacogenetic studies. PloS one 73 19956635
1999 Position of a 'green-red' hybrid gene in the visual pigment array determines colour-vision phenotype. Nature genetics 73 10319869
1992 Defective colour vision associated with a missense mutation in the human green visual pigment gene. Nature genetics 71 1302020
2012 Nek9 phosphorylation of NEDD1/GCP-WD contributes to Plk1 control of γ-tubulin recruitment to the mitotic centrosome. Current biology : CB 68 22818914
2022 Mechanisms of Cannabidiol (CBD) in Cancer Treatment: A Review. Biology 65 35741337
2004 CXCR1-binding chemokines in inflammatory bowel diseases: down-regulated IL-8/CXCL8 production by leukocytes in Crohn's disease and selective GCP-2/CXCL6 expression in inflamed intestinal tissue. European journal of immunology 65 15214047
2004 A concentrated aglycone isoflavone preparation (GCP) that demonstrates potent anti-prostate cancer activity in vitro and in vivo. Clinical cancer research : an official journal of the American Association for Cancer Research 64 15297432
2008 The human CXC chemokine granulocyte chemotactic protein 2 (GCP-2)/CXCL6 possesses membrane-disrupting properties and is antibacterial. Antimicrobial agents and chemotherapy 63 18443119
2012 The role of glutamate signaling in pain processes and its regulation by GCP II inhibition. Current medicinal chemistry 62 22304711
2012 G protein-coupled receptors participate in cytokinesis. Cytoskeleton (Hoboken, N.J.) 60 22888021
2011 Interaction between non-psychotropic cannabinoids in marihuana: effect of cannabigerol (CBG) on the anti-nausea or anti-emetic effects of cannabidiol (CBD) in rats and shrews. Psychopharmacology 60 21243485
2022 Extracellular vesicles of cannabis with high CBD content induce anticancer signaling in human hepatocellular carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 59 35667235
2018 The non-psychoactive phytocannabinoid cannabidiol (CBD) attenuates pro-inflammatory mediators, T cell infiltration, and thermal sensitivity following spinal cord injury in mice. Cellular immunology 57 29784129
2005 Lipid peroxides, superoxide dismutase and circulating IL-8 and GCP-2 in patients with severe obstructive sleep apnea: a pilot study. Sleep & breathing = Schlaf & Atmung 57 15988615
1989 Analysis of fusion gene and encoded photopigment of colour-blind humans. Nature 53 2574415
2011 Isotypic neutralizing antibodies against mouse GCP-2/CXCL6 inhibit melanoma growth and metastasis. Cancer letters 52 21236563
2021 CBD activation of TRPV1 induces oxidative signaling and subsequent ER stress in breast cancer cell lines. Biotechnology and applied biochemistry 49 33604949
2020 A Critical Review of the Role of the Cannabinoid Compounds Δ9-Tetrahydrocannabinol (Δ9-THC) and Cannabidiol (CBD) and their Combination in Multiple Sclerosis Treatment. Molecules (Basel, Switzerland) 48 33113776
2022 Cannabidiol (CBD) Dosing: Plasma Pharmacokinetics and Effects on Accumulation in Skeletal Muscle, Liver and Adipose Tissue. Nutrients 45 35631242
2020 Cannabidiol (CBD) enhanced the hippocampal immune response and autophagy of APP/PS1 Alzheimer's mice uncovered by RNA-seq. Life sciences 43 33096116
1995 Expression of the cbbLcbbS and cbbM genes and distinct organization of the cbb Calvin cycle structural genes of Rhodobacter capsulatus. Archives of microbiology 42 8588741
2022 Label accuracy of unregulated cannabidiol (CBD) products: measured concentration vs. label claim. Journal of cannabis research 41 35658956
2020 CBD modulates DNA methylation in the prefrontal cortex and hippocampus of mice exposed to forced swim. Behavioural brain research 41 32348868
2010 X-linked cone dystrophy caused by mutation of the red and green cone opsins. American journal of human genetics 41 20579627
2021 Food effects on the formulation, dosing, and administration of cannabidiol (CBD) in humans: A systematic review of clinical studies. Pharmacotherapy 39 33583102
2010 Variable retinal phenotypes caused by mutations in the X-linked photopigment gene array. Investigative ophthalmology & visual science 39 20220053
2002 Morphine tolerance and reward but not expression of morphine dependence are inhibited by the selective glutamate carboxypeptidase II (GCP II, NAALADase) inhibitor, 2-PMPA. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 39 12629525
2012 Synthesis of galactooligosaccharides by CBD fusion β-galactosidase immobilized on cellulose. Bioresource technology 38 22525263
2016 Cannabidiol (CBD) induces functional Tregs in response to low-level T cell activation. Cellular immunology 37 27865421
2023 Review of the oral toxicity of cannabidiol (CBD). Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 36 37088127
2022 Cannabinoid CB1 Receptor Involvement in the Actions of CBD on Anxiety and Coping Behaviors in Mice. Pharmaceuticals (Basel, Switzerland) 35 35455470
2022 Fabrication and Preliminary In Vitro Evaluation of 3D-Printed Alginate Films with Cannabidiol (CBD) and Cannabigerol (CBG) Nanoparticles for Potential Wound-Healing Applications. Pharmaceutics 35 36015263
2019 DMH-CBD, a cannabidiol analog with reduced cytotoxicity, inhibits TNF production by targeting NF-kB activity dependent on A2A receptor. Toxicology and applied pharmacology 35 30796934
2009 The action of 11-cis-retinol on cone opsins and intact cone photoreceptors. The Journal of biological chemistry 34 19386593
2016 Cone Photoreceptor Structure in Patients With X-Linked Cone Dysfunction and Red-Green Color Vision Deficiency. Investigative ophthalmology & visual science 33 27447086
2002 Novel missense mutations in red/green opsin genes in congenital color-vision deficiencies. Biochemical and biophysical research communications 33 12051694
2021 CBD Alleviates Liver Injuries in Alcoholics With High-Fat High-Cholesterol Diet Through Regulating NLRP3 Inflammasome-Pyroptosis Pathway. Frontiers in pharmacology 32 34630100
2022 Differential Effects of D9 Tetrahydrocannabinol (THC)- and Cannabidiol (CBD)-Based Cannabinoid Treatments on Macrophage Immune Function In Vitro and on Gastrointestinal Inflammation in a Murine Model. Biomedicines 31 35892693
2021 Effects of cannabinoid (CBD) on blood brain barrier permeability after brain injury in rats. Brain research 31 34289379
2014 GCP-WD mediates γ-TuRC recruitment and the geometry of microtubule nucleation in interphase arrays of Arabidopsis. Current biology : CB 31 25438942
2008 Granulocyte chemotactic protein 2 (gcp-2/cxcl6) complements interleukin-8 in periodontal disease. Journal of periodontal research 31 18842116
2022 The Anti-Inflammatory Effects of Cannabidiol (CBD) on Acne. Journal of inflammation research 30 35535052
2007 Stimulation of angiostatic platelet factor-4 variant (CXCL4L1/PF-4var) versus inhibition of angiogenic granulocyte chemotactic protein-2 (CXCL6/GCP-2) in normal and tumoral mesenchymal cells. Journal of leukocyte biology 30 17827342
2021 Effect of Cannabidiol (CBD) on Canine Inflammatory Response: An Ex Vivo Study on LPS Stimulated Whole Blood. Veterinary sciences 29 34564578
2020 Developmental exposure to cannabidiol (CBD) alters longevity and health span of zebrafish (Danio rerio). GeroScience 29 32221778
2016 De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy. Scientific reports 29 27339364
2023 Cautious Hope for Cannabidiol (CBD) in Rheumatology Care. Arthritis care & research 28 32144889
2013 Impact of enzymatic and alkaline hydrolysis on CBD concentration in urine. Analytical and bioanalytical chemistry 28 23494274
2008 Constitutive expression of the antibacterial CXC chemokine GCP-2/CXCL6 by epithelial cells of the male reproductive tract. Journal of reproductive immunology 28 18809212
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