Affinage

OPRM1

Mu-type opioid receptor · UniProt P35372

Length
400 aa
Mass
44.8 kDa
Annotated
2026-04-29
100 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OPRM1 encodes the mu-opioid receptor (MOR), a Gi/o-coupled GPCR that is the principal mediator of opioid analgesia and a critical modulator of reward, social behavior, and nociceptive processing. The receptor is preferentially targeted to somatodendritic compartments of neurons, with predominant expression on excitatory interneurons in the spinal dorsal horn, and couples to adenylate cyclase inhibition and GIRK channel activation (PMID:7751913, PMID:8938756, PMID:24527749). Extensive alternative splicing generates isoforms with distinct regional distributions and desensitization properties—including exon 11-containing variants selectively required for heroin, M6G, and fentanyl but not morphine analgesia (PMID:9466465, PMID:19273844). OPRM1 expression is regulated at multiple levels: post-transcriptionally by miRNA-23b-mediated translational repression that is upregulated by chronic morphine (PMID:18716031, PMID:19144786), translationally by an upstream AUG-initiated isoform degraded via the ubiquitin–proteasome pathway (PMID:19609488), and epigenetically by MBD1/DNMT3a- and MeCP2/HDAC1-dependent promoter silencing in DRG neurons (PMID:30266739, PMID:34803588), while the common A118G (N40D) variant reduces receptor mRNA and protein levels and alters morphine-induced antinociception and social behavior in knock-in mice (PMID:16046395, PMID:19528658, PMID:25716856).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1995 High

    Establishing that MOR is a polarized neuronal protein resolved how a single receptor could mediate both pre- and postsynaptic opioid actions across brain regions.

    Evidence Immunohistochemistry with C-terminal antisera and MAP2 double-labeling in rat brain sections

    PMID:7751913

    Open questions at the time
    • Sorting signals directing somatodendritic vs. axonal targeting not identified
    • No live-cell trafficking data
  2. 1996 High

    Identifying MOR expression predominantly on non-GABAergic, non-glycinergic dorsal horn neurons established that mu-opioid analgesia operates by inhibiting excitatory interneurons relaying nociceptive input.

    Evidence Pre-embedding MOR1 immunocytochemistry combined with post-embedding GABA/glycine immunolabeling in spinal cord

    PMID:8938756

    Open questions at the time
    • Specific excitatory interneuron subtypes not molecularly defined
    • No electrophysiological confirmation of opioid-mediated inhibition of these neurons
  3. 1998 High

    Demonstrating that alternatively spliced MOR isoforms (MOR1 vs. MOR1B) have distinct CNS distributions and differ in agonist-induced desensitization revealed that C-terminal tail diversity generates functionally distinct receptor populations.

    Evidence Isoform-specific antibodies with immunocytochemistry and adenylate cyclase coupling assays in rat brain

    PMID:9466465

    Open questions at the time
    • Molecular basis of differential desensitization (phosphorylation sites, arrestin recruitment) not mapped
    • In vivo behavioral consequence of MOR1B-selective signaling unknown
  4. 2005 High

    Quantifying the A118G (N40D) variant's effect on mRNA and protein levels resolved a longstanding debate by showing >10-fold reduced protein with only modest mRNA decrease, implicating a transcriptional or mRNA maturation defect rather than altered stability.

    Evidence Allele-specific mRNA quantification in human autopsy brain, CHO transfection, Western blot, binding assays, actinomycin D stability assay

    PMID:16046395

    Open questions at the time
    • Exact step in mRNA biogenesis affected (splicing, export, transcription initiation) not pinpointed
    • N40D effect on receptor trafficking and signaling efficacy in neurons not tested
  5. 2007 High

    Discovering that endothelial MOR transactivates S1P3 via RhoA/ROCK to regulate vascular permeability extended MOR function beyond neuronal signaling to peripheral barrier regulation.

    Evidence siRNA knockdown of MOR and S1P3 in human pulmonary endothelial cells with in vitro permeability and in vivo lung vascular assays

    PMID:17395891

    Open questions at the time
    • Direct physical interaction between MOR and S1P3 not shown
    • Relevance to clinical opioid-induced pulmonary edema not established
  6. 2008 High

    Identification of miRNA-23b as a translational repressor of MOR1 via a 3′-UTR K box motif established the first post-transcriptional regulatory mechanism for MOR that operates at the polysome level without altering mRNA abundance.

    Evidence Reporter assays with MOR1 3′-UTR, polysome fractionation, and miRNA-23b knockdown in NS20Y neuroblastoma cells

    PMID:18716031

    Open questions at the time
    • Other miRNAs targeting MOR 3′-UTR not systematically evaluated
    • In vivo neuronal relevance of miR-23b regulation not demonstrated
  7. 2009 High

    Four contemporaneous studies collectively established that (1) chronic morphine upregulates miR-23b to repress MOR translation, (2) an upstream AUG produces a proteasomally degraded long MOR isoform that competes with canonical translation, (3) exon 11-containing splice variants are selectively required for heroin/M6G/fentanyl analgesia, and (4) the A112G knock-in mouse recapitulates reduced MOR expression with sex-specific behavioral consequences—together revealing multilayered transcriptional, translational, and splice-variant-specific control of opioid pharmacology.

    Evidence Morphine-treated polysome/reporter assays; upstream AUG mutagenesis with proteasome inhibition; exon 11 knockout mice with tail-flick/hot-plate assays; A112G knock-in mice with CPP and locomotor assays

    PMID:19144786 PMID:19273844 PMID:19528658 PMID:19609488

    Open questions at the time
    • In vivo stoichiometry of upstream-AUG long form vs. canonical MOR unknown
    • Whether exon 11 variants signal through distinct G-protein subtypes not tested
    • Molecular basis of sex-specific effects of A112G on reward circuitry unresolved
  8. 2012 Medium

    Genetic epistasis showing that Oprm1 reduction rescued social deficits in MECP2 duplication mice positioned MOR as a functionally relevant transcriptional target of MeCP2 in social behavior circuits.

    Evidence MECP2 duplication mice crossed with Oprm1 reduction; behavioral assays for social interaction

    PMID:22231481

    Open questions at the time
    • Whether MeCP2 directly binds the Oprm1 promoter in social-behavior-relevant brain regions not shown in this study
    • Mechanism by which reduced Oprm1 rescues social behavior unclear
  9. 2014 Medium

    Identification of filamin A (FLNA) as a MOR-1K interaction partner that redistributes this excitatory splice variant to the cell surface provided the first evidence that cytoskeletal scaffolding regulates MOR isoform trafficking.

    Evidence FLNA overexpression in HEK293 cells with subcellular imaging of MOR-1K localization

    PMID:24413261

    Open questions at the time
    • FLNA–MOR-1K interaction not validated by reciprocal pulldown or endogenous co-IP
    • Functional consequence of surface redistribution on excitatory signaling not tested
    • Single overexpression system limits generalizability
  10. 2015 High

    Demonstrating that A112G knock-in mice show increased sociability and resilience to social defeat—blocked by naloxone—established that the A118G variant alters endogenous opioid tone governing social reward circuitry.

    Evidence Knock-in mice with social interaction/dominance assays, social defeat, c-fos mapping in NAc and PAG, naloxone challenge

    PMID:25716856

    Open questions at the time
    • Which endogenous opioid peptide drives the altered tone not identified
    • Circuit-specific mechanisms in NAc vs. PAG not dissected
  11. 2018 High

    Demonstrating that MBD1 recruits DNMT3a to the Oprm1 promoter in DRG neurons to silence transcription, with bidirectional effects on pain behavior, identified a specific epigenetic writer complex controlling peripheral MOR expression.

    Evidence MBD1 conditional knockout and DRG-specific overexpression, ChIP for DNMT3a at Oprm1 promoter, behavioral pain assays

    PMID:30266739

    Open questions at the time
    • Specific CpG sites methylated by recruited DNMT3a not mapped at single-nucleotide resolution
    • Whether MBD1/DNMT3a complex also operates in CNS neurons unknown
  12. 2021 High

    Showing that MeCP2 recruits HDAC1 to deacetylate histone H3 at the Oprm1 promoter after nerve injury, and that HDAC inhibition restores MOR expression and morphine analgesia, defined a second epigenetic silencing axis complementing the MBD1/DNMT3a pathway.

    Evidence MeCP2 knockdown/overexpression in DRG, ChIP for MeCP2, HDAC1, and H3 acetylation at Oprm1 promoter, SAHA treatment, behavioral analgesia assays

    PMID:34803588

    Open questions at the time
    • Crosstalk between MBD1/DNMT3a and MeCP2/HDAC1 pathways at the same promoter not examined
    • Whether these mechanisms explain clinical opioid tolerance after nerve injury untested
  13. 2021 High

    Heterozygous Oprm1 loss increasing inhibitory synaptic transmission onto D2-MSNs and impairing social behavior revealed a specific circuit mechanism linking partial MOR deficiency to social reward deficits.

    Evidence Oprm1+/- mice, electrophysiology of D2-MSN inhibitory currents, FISH for gephyrin, social CPP and interaction assays

    PMID:34301826

    Open questions at the time
    • Whether increased inhibition is cell-autonomous or network-driven not resolved
    • Sufficiency of D2-MSN inhibitory changes for social deficits not tested with circuit-specific rescue

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how the multiple epigenetic, post-transcriptional, and splice-variant mechanisms are integrated in single neurons to set MOR expression levels; which endogenous opioid peptides preferentially activate exon 11-containing vs. canonical isoforms; and the structural basis by which the N40D substitution reduces protein yield.
  • No integrative model of combinatorial MOR expression regulation in individual cell types
  • Endogenous ligand selectivity for splice variants unknown
  • Structural mechanism of N40D-mediated protein reduction unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-112316 Neuronal System 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 3
Partners
DNMT3AFLNAHDAC1MBD1MECP2S1PR3

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 MOR1 (OPRM1) protein is preferentially targeted to the somatodendritic domain of neurons in most brain regions, as determined by double-labeling with MAP2; however, discrete neuronal populations (including some primary afferent neurons) target MOR1 to axons, establishing both pre- and postsynaptic localization. Anti-peptide antisera against MOR1 C-terminal peptide, immunohistochemistry, double-labeling with MAP2, Western blot, immunoisolation The Journal of neuroscience High 7751913
1998 Two MOR1 isoforms (MOR1 and MOR1B), arising from alternative splicing of the cytoplasmic tail, show strikingly different distributions in the rat CNS: MOR1 is widely distributed in pain-controlling regions (spinal cord dorsal horn, raphe nuclei, periaqueductal gray), while MOR1B is predominantly localized to the olfactory bulb external plexiform layer, and the isoforms differ in agonist-induced desensitization of coupling to adenylate cyclase. Isoform-specific polyclonal antibodies, immunocytochemical localization, adenylate cyclase coupling assay Neuroscience High 9466465
1996 MOR1 immunoreactivity in the superficial dorsal horn is restricted predominantly to non-GABAergic, non-glycinergic neurons (94% GABA/glycine-negative), suggesting that mu-opioid agonists inhibit excitatory interneurons that relay nociceptive input. Pre-embedding immunocytochemistry for MOR1 combined with post-embedding immunolabeling for GABA and glycine Neuroscience High 8938756
2005 The OPRM1 A118G (N40D) variant results in >10-fold lower protein levels and ~1.5-fold lower mRNA levels compared to the A118 allele when transfected into CHO cells; the reduction is not due to altered mRNA stability but to a defect in transcription or mRNA maturation, and allelic imbalance (A118 allele 1.5–2.5-fold more abundant) was confirmed in human autopsy brain tissue. Allele-specific mRNA quantification in human brain tissue, CHO cell transfection with coding-region cDNA variants, Western blot, receptor binding assay, actinomycin D mRNA stability assay The Journal of biological chemistry High 16046395
2008 miRNA23b binds to a K box motif in the 3'-UTR of MOR1 mRNA and suppresses MOR1 protein production by inhibiting MOR1 mRNA association with polysomes (translational repression), without altering mRNA levels. Reporter assays with MOR1 3'-UTR, polysome fractionation, miRNA23b knockdown in NS20Y neuroblastoma cells FASEB journal High 18716031
2009 Long-term morphine treatment increases miRNA23b expression in a dose- and time-dependent manner, which in turn represses MOR1 mRNA association with polysomes via the MOR1 3'-UTR, providing a post-transcriptional mechanism for morphine-induced downregulation of MOR expression. miRNA23b quantification after morphine treatment, polysome-mRNA association assay, translational luciferase reporter assay with MOR1 3'-UTR Molecular pharmacology High 19144786
2009 OPRM1 exon 11-associated splice variants (lacking exon 1) are selectively required for analgesia produced by heroin, morphine-6β-glucuronide (M6G), and fentanyl, but not morphine or methadone, as demonstrated by exon 11 knockout mice showing markedly diminished heroin/M6G/fentanyl analgesia with normal morphine analgesia. Exon 11 knockout mouse model, radiant heat tail-flick and hot-plate analgesic assays, gastrointestinal transit inhibition assay Proceedings of the National Academy of Sciences High 19273844
2009 A mouse model carrying the Oprm1 A112G SNP (equivalent to human A118G) shows reduced MOR mRNA and protein levels and reduced morphine-mediated antinociception and hyperactivity, with sex-specific reductions in morphine reward and naloxone-precipitated withdrawal aversion. Knock-in mouse model, quantitative PCR, Western blot, antinociception assays, locomotor sensitization, conditioned place preference Proceedings of the National Academy of Sciences High 19528658
2007 Attenuation of endothelial barrier disruption by mu opioid receptor (MOR/OPRM1) agonists is mediated via RhoA/ROCK-dependent threonine phosphorylation and transactivation of the sphingosine 1-phosphate receptor S1P3; silencing mOP-R with siRNA attenuated morphine- and DAMGO-induced barrier disruption, while S1P3 silencing abolished permeability responses to all edemagenic agonists. siRNA knockdown of mOP-R and S1P3 in human pulmonary endothelial cells, in vitro barrier permeability assay, S1P3 phosphorylation assay, in vivo murine lung vascular permeability American journal of respiratory cell and molecular biology High 17395891
2009 The 5'-UTR of OPRM1 contains an in-frame upstream translation initiation codon that produces a longer MOR protein isoform with a short half-life due to ubiquitin-proteasome degradation; initiation at the upstream AUG decreases translation from the main AUG, and mutation of the second and third lysines of the long form reduces ubiquitin-dependent proteasome degradation. Reporter and degradation assays, mutagenesis of upstream AUG and lysine residues, proteasome inhibition, in vitro and in vivo translation studies Cellular and molecular life sciences High 19609488
2008 Increased DNA methylation at the OPRM1 promoter (at CpG sites located in potential Sp1 transcription factor-binding sites) is observed in lymphocytes of methadone-maintained former heroin addicts compared to controls, suggesting that methylation of these sites may reduce OPRM1 expression. Bisulfite sequencing of OPRM1 promoter CpG dinucleotides in blood DNA from 194 cases and 135 controls Neuropsychopharmacology Medium 18650805
2018 MBD1 (methyl-CpG-binding domain protein 1) represses Oprm1 gene expression in DRG primary sensory neurons by recruiting DNA methyltransferase DNMT3a to the Oprm1 promoter; MBD1-deficient mice show reduced acute and neuropathic pain responses, and DRG-specific MBD1 overexpression produces pain hypersensitivity and reduces Oprm1 expression. MBD1 conditional knockout and overexpression in DRG neurons, ChIP assay (DNMT3a recruitment), behavioral pain assays, quantitative PCR The Journal of neuroscience High 30266739
2021 MeCP2 upregulation in injured DRG recruits HDAC1 to hypermethylated regions of the Oprm1 promoter, reduces histone H3 acetylation at the Oprm1 promoter, and suppresses Oprm1 transcription, thereby reducing MOR expression and morphine analgesia; HDAC1 inhibition with SAHA restored MOR expression. MeCP2 knockdown and viral vector overexpression in DRG, ChIP assay for MeCP2 and HDAC1 binding and H3 acetylation at Oprm1 promoter, HDAC inhibitor treatment, morphine analgesia behavioral assay Frontiers in neuroscience High 34803588
2012 In the MECP2 duplication mouse model, increased MeCP2 levels reduce Oprm1 expression; reducing Oprm1 expression specifically improved abnormal social behavior deficits, establishing that Oprm1 downregulation downstream of MeCP2 overexpression mediates social behavior phenotypes. Genetic epistasis using MECP2 duplication mice with reduced Oprm1 expression; behavioral assays for social behavior Nature genetics Medium 22231481
2021 Heterozygous genetic knockout of Oprm1 (Oprm1+/-) in mice increases inhibitory synaptic transmission in D2-MSNs of the nucleus accumbens (sex-dependently), increases gephyrin mRNA and inhibitory synaptic puncta density at D2-MSN cell bodies, and diminishes social conditioned place preference and reciprocal social interaction. Heterozygous Oprm1 knockout mice, electrophysiology of inhibitory synaptic transmission, fluorescence in situ hybridization, behavioral assays (social CPP, social interaction, social preference) The Journal of neuroscience High 34301826
2014 The OPRM1 N-terminal splice variant MOR-1K, which mediates excitatory cellular signaling, shows cell-type-specific expression segregation in the nervous system; in HIV-infected individuals with HIVE, MOR-1K expression is upregulated and correlates with neurocognitive impairment; filamin A (FLNA) was identified as an interaction partner that redistributes MOR-1K from intracellular compartments to the cell surface when overexpressed. RT-PCR expression analysis, microarray network analysis, FLNA overexpression in HEK293 cells with subcellular localization imaging AIDS Medium 24413261
2014 Multiple non-synonymous SNPs in OPRM1 coding regions alter receptor expression, coupling to second messengers (e.g., cAMP inhibition, GIRK activation), and agonist-dependent regulation in vitro, indicating that structural changes from SNPs affect functional receptor properties. In vitro transfection of OPRM1 SNP variants, radioligand binding, cAMP assay, GIRK current recording, receptor internalization assays British journal of pharmacology Medium 24527749
2023 Adeno-associated viral vectors driven by the mouse or human OPRM1 promoter (MORp) selectively transduce endogenous MOR+ neurons in mouse brain, spinal cord, and periphery, enabling fiber photometry, chemogenetics, and intersectional genetic strategies; the human MORp efficiently transduced macaque cortical OPRM1+ cells and human iPSC-derived nociceptors. AAV-MORp viral constructs, in vivo and in vitro transduction efficiency/selectivity validation, fiber photometry, DREADD-based chemogenetics, immunohistochemistry Nature communications High 37704594
2015 Oprm1 A112G knock-in mice (equivalent to human A118G) show increased sociability, dominance, and resilience to social defeat; protection from social defeat correlated with greater c-fos induction in nucleus accumbens and periaqueductal gray; naloxone pretreatment blocked the increase in social affiliation in G-allele carriers, implicating altered endogenous opioid tone. Knock-in mouse model, social interaction and dominance assays, social defeat paradigm, intracranial self-stimulation, c-fos immunohistochemistry, naloxone pharmacological challenge The Journal of neuroscience High 25716856
2021 Lung cancer cell-derived exosomal let-7d-5p is taken up by DRG neurons and inhibits OPRM1 protein levels, contributing to cancer-induced bone pain; this was confirmed in vivo showing exosomal let-7d-5p mediates generation and maintenance of bone pain through OPRM1 suppression. Exosome isolation from A549/NCI-H1299 cells, qRT-PCR, in vitro DRG neuron uptake, Western blot of OPRM1, in vivo bone pain model Frontiers in cell and developmental biology Medium 34124049
2016 Mu-opioid receptor (MOP)-mediated G-protein signaling (measured by [35S]GTPγS binding with DAMGO) is significantly impaired in thalamus, olfactory bulb, prefrontal cortex, and hippocampus in a rat model of schizophrenia, and the potency of DAMGO to activate G-proteins is also reduced in these regions. [35S]GTPγS binding assay in brain membrane preparations from schizophrenia model rats vs. controls, DAMGO as selective MOP agonist Neuroscience letters Medium 26946106

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Distribution and targeting of a mu-opioid receptor (MOR1) in brain and spinal cord. The Journal of neuroscience : the official journal of the Society for Neuroscience 542 7751913
2005 Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G. The Journal of biological chemistry 450 16046395
2021 Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clinical pharmacology and therapeutics 300 33387367
2007 Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief. Clinical pharmacology and therapeutics 245 17898703
2003 The multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) exporter superfamily. European journal of biochemistry 195 12603313
2013 Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome. JAMA 149 23632726
2009 Mouse model of OPRM1 (A118G) polymorphism has sex-specific effects on drug-mediated behavior. Proceedings of the National Academy of Sciences of the United States of America 143 19528658
2008 Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates. Proceedings of the National Academy of Sciences of the United States of America 137 18378897
2020 Association of OPRM1 Functional Coding Variant With Opioid Use Disorder: A Genome-Wide Association Study. JAMA psychiatry 134 32492095
2008 Increased OPRM1 DNA methylation in lymphocytes of methadone-maintained former heroin addicts. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 127 18650805
2008 Analgesic requirements after major abdominal surgery are associated with OPRM1 gene polymorphism genotype and haplotype. Pharmacogenomics 119 19018716
2012 Crh and Oprm1 mediate anxiety-related behavior and social approach in a mouse model of MECP2 duplication syndrome. Nature genetics 116 22231481
2010 OPRM1 SNP (A118G): involvement in disease development, treatment response, and animal models. Drug and alcohol dependence 114 20074870
2005 Polymorphism of mu-opioid receptor gene (OPRM1:c.118A>G) does not protect against opioid-induced respiratory depression despite reduced analgesic response. Anesthesiology 111 15731588
2002 Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin. Human mutation 108 11933204
2011 Human Mu Opioid Receptor (OPRM1 A118G) polymorphism is associated with brain mu-opioid receptor binding potential in smokers. Proceedings of the National Academy of Sciences of the United States of America 107 21576462
2009 Association between OPRM1 gene polymorphisms and fentanyl sensitivity in patients undergoing painful cosmetic surgery. Pain 106 19783098
2002 The plant cytoskeleton: recent advances in the study of the plant microtubule-associated proteins MAP-65, MAP-190 and the Xenopus MAP215-like protein, MOR1. Plant molecular biology 102 12516862
2007 Attenuation of vascular permeability by methylnaltrexone: role of mOP-R and S1P3 transactivation. American journal of respiratory cell and molecular biology 94 17395891
2009 Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions. Proceedings of the National Academy of Sciences of the United States of America 93 19273844
2011 Elevated levels of DNA methylation at the OPRM1 promoter in blood and sperm from male opioid addicts. Journal of opioid management 92 21957825
2013 Pharmacogenetics of OPRM1. Pharmacology, biochemistry, and behavior 77 24201053
2012 Interacting effects of naltrexone and OPRM1 and DAT1 variation on the neural response to alcohol cues. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 73 23032071
2009 Long-term morphine treatment decreases the association of mu-opioid receptor (MOR1) mRNA with polysomes through miRNA23b. Molecular pharmacology 71 19144786
2013 OPRM1 rs1799971 polymorphism and opioid dependence: evidence from a meta-analysis. Pharmacogenomics 69 23651028
2008 MOR1, the Arabidopsis thaliana homologue of Xenopus MAP215, promotes rapid growth and shrinkage, and suppresses the pausing of microtubules in vivo. Journal of cell science 69 19033380
2012 Ethnicity interacts with the OPRM1 gene in experimental pain sensitivity. Pain 67 22717102
1998 Immunolocalization of two mu-opioid receptor isoforms (MOR1 and MOR1B) in the rat central nervous system. Neuroscience 66 9466465
1996 The mu-opioid receptor (MOR1) is mainly restricted to neurons that do not contain GABA or glycine in the superficial dorsal horn of the rat spinal cord. Neuroscience 64 8938756
2022 Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond. Scientific reports 61 36207451
1991 Photoprotection and 5-MOP photochemoprotection from UVR-induced DNA damage in humans: the role of skin type. The Journal of investigative dermatology 58 1919058
2011 Mu-opioid receptor (OPRM1) variation, oxytocin levels and maternal attachment in free-ranging rhesus macaques Macaca mulatta. Behavioral neuroscience 54 21463018
2011 Variation in the μ-opioid receptor gene (OPRM1) moderates the influence of early maternal care on fearful attachment. Social cognitive and affective neuroscience 54 21742765
2015 Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1. Biological psychiatry 53 25744370
2018 MBD1 Contributes to the Genesis of Acute Pain and Neuropathic Pain by Epigenetic Silencing of Oprm1 and Kcna2 Genes in Primary Sensory Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 50 30266739
2014 Influence of UGT2B7, OPRM1 and ABCB1 gene polymorphisms on postoperative morphine consumption. Basic & clinical pharmacology & toxicology 50 24703092
2013 The role of hydromorphone and OPRM1 in postoperative pain relief with hydrocodone. Pain physician 48 23703421
2012 Hypermethylation of OPRM1 promoter region in European Americans with alcohol dependence. Journal of human genetics 48 22914673
2008 Post-transcriptional regulation of mouse mu opioid receptor (MOR1) via its 3' untranslated region: a role for microRNA23b. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 48 18716031
2010 OPRM1 and CYP2B6 gene variants as risk factors in methadone-related deaths. Clinical pharmacology and therapeutics 47 20668445
2013 Gene polymorphisms of OPRM1 A118G and ABCB1 C3435T may influence opioid requirements in Chinese patients with cancer pain. Asian Pacific journal of cancer prevention : APJCP 46 23803057
2011 CYP2B6 and OPRM1 gene variations predict methadone-related deaths. Addiction biology 46 21158011
2004 Characterization of a 200 kDa microtubule-associated protein of tobacco BY-2 cells, a member of the XMAP215/MOR1 family. Plant & cell physiology 46 15509846
2013 Initial evidence that OPRM1 genotype moderates ventral and dorsal striatum functional connectivity during alcohol cues. Alcoholism, clinical and experimental research 45 23876228
2019 Overexpression of the long non-coding RNA Oprm1 alleviates apoptosis from cerebral ischemia-reperfusion injury through the Oprm1/miR-155/GATA3 axis. Artificial cells, nanomedicine, and biotechnology 40 31187646
2014 Associations of OPRM1 A118G and alcohol sensitivity with intravenous alcohol self-administration in young adults. Addiction biology 40 25039301
2007 Evaluation of OPRM1 variants in heroin dependence by family-based association testing and meta-analysis. Drug and alcohol dependence 40 17416470
2019 OPRM1 rs1799971, COMT rs4680, and FAAH rs324420 genes interact with placebo procedures to induce hypoalgesia. Pain 39 31335650
2018 Epigenetic variation in OPRM1 gene in opioid-exposed mother-infant dyads. Genes, brain, and behavior 38 29575474
2020 Effect of short-term prescription opioids on DNA methylation of the OPRM1 promoter. Clinical epigenetics 37 32493461
2017 Increased DNA Methylation of ABCB1, CYP2D6, and OPRM1 Genes in Newborn Infants of Methadone-Maintained Opioid-Dependent Mothers. The Journal of pediatrics 37 28867064
2015 Mouse model of OPRM1 (A118G) polymorphism increases sociability and dominance and confers resilience to social defeat. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 25716856
2014 Differential expressions of the alternatively spliced variant mRNAs of the µ opioid receptor gene, OPRM1, in brain regions of four inbred mouse strains. PloS one 36 25343478
2018 Suggestive association between OPRM1 and impulse control disorders in Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society 35 30444952
2017 Elevated levels of DNA methylation at the OPRM1 promoter region in men with opioid use disorder. The American journal of drug and alcohol abuse 34 28121474
2014 Interactive effects of OPRM1 and DAT1 genetic variation on subjective responses to alcohol. Alcohol and alcoholism (Oxford, Oxfordshire) 33 24421289
2007 Identification of five mouse mu-opioid receptor (MOR) gene (Oprm1) splice variants containing a newly identified alternatively spliced exon. Gene 32 17398041
2021 μ-Opioid Receptor (Oprm1) Copy Number Influences Nucleus Accumbens Microcircuitry and Reciprocal Social Behaviors. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 34301826
2019 Neurobehavioral effects of neonatal opioid exposure in mice: Influence of the OPRM1 SNP. Addiction biology 29 31267641
2013 Low frequency genetic variants in the μ-opioid receptor (OPRM1) affect risk for addiction to heroin and cocaine. Neuroscience letters 28 23454283
2018 Elevated methylation of OPRM1 and OPRL1 genes in Alzheimer's disease. Molecular medicine reports 27 30152845
2006 Identification of three mouse mu-opioid receptor (MOR) gene (Oprm1) splice variants containing a newly identified alternatively spliced exon. Gene 27 17156941
1996 Kinetic analysis of apoptosis induction in human cell lines by UVA and 8-MOP. Photochemistry and photobiology 27 8628747
2021 Alternative Pre-mRNA Splicing of the Mu Opioid Receptor Gene, OPRM1: Insight into Complex Mu Opioid Actions. Biomolecules 26 34680158
2019 The Relevance of the OPRM1 118A>G Genetic Variant for Opioid Requirement in Pain Treatment: A Meta-Analysis. Pain physician 26 31337162
2015 μ-Opioid receptor gene (OPRM1) polymorphism in patients with breast cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 26 25618602
2014 Differential expression of the alternatively spliced OPRM1 isoform μ-opioid receptor-1K in HIV-infected individuals. AIDS (London, England) 26 24413261
2014 MOR1 expression in gastric cancer: a biomarker associated with poor outcome. Clinical and translational science 26 25441763
2000 Potato mop-top virus RNA can move long distance in the absence of coat protein: evidence from resistant, transgenic plants. Molecular plant-microbe interactions : MPMI 25 10656594
2016 Evidence for nociceptin/orphanin FQ (NOP) but not µ (MOP), δ (DOP) or κ (KOP) opioid receptor mRNA in whole human blood. British journal of anaesthesia 24 26865135
2012 A systematic review of the A118G (Asn40Asp) variant of OPRM1 in relation to smoking initiation, nicotine dependence and smoking cessation. Pharmacogenomics 24 22676196
1996 4'-Methyl derivatives of 5-MOP and 5-MOA: synthesis, photoreactivity, and photobiological activity. Journal of medicinal chemistry 24 8893844
2021 Lung Cancer Cell-Derived Exosomal let-7d-5p Down-Regulates OPRM1 to Promote Cancer-Induced Bone Pain. Frontiers in cell and developmental biology 23 34124049
2018 The opioid receptor mu 1 (OPRM1) rs1799971 and catechol-O-methyltransferase (COMT) rs4680 as genetic markers for placebo analgesia. Pain 23 30130297
2023 Human OPRM1 and murine Oprm1 promoter driven viral constructs for genetic access to μ-opioidergic cell types. Nature communications 22 37704594
2018 Fundamental Considerations for Genetically-Guided Pain Management with Opioids Based on CYP2D6 and OPRM1 Polymorphisms. Pain physician 22 30508992
2016 Mu-Opioid (MOP) receptor mediated G-protein signaling is impaired in specific brain regions in a rat model of schizophrenia. Neuroscience letters 22 26946106
2015 Effect of gene polymorphism of COMT and OPRM1 on the preoperative pain sensitivity in patients with cancer. International journal of clinical and experimental medicine 22 26309696
2015 OPRM1 and ABCB1 polymorphisms and their effect on postoperative pain relief with piritramide. Physiological research 22 26681082
2021 MeCP2 Epigenetic Silencing of Oprm1 Gene in Primary Sensory Neurons Under Neuropathic Pain Conditions. Frontiers in neuroscience 21 34803588
2020 OPRM1 and COMT polymorphisms: implications on postoperative acute, chronic and experimental pain after cardiac surgery. Pharmacogenomics 21 31967515
2020 LncRNA Oprm1 overexpression attenuates myocardial ischemia/reperfusion injury by increasing endogenous hydrogen sulfide via Oprm1/miR-30b-5p/CSE axis. Life sciences 21 32437793
2013 Lack of association between DRD2 and OPRM1 genotypes and adiposity. International journal of obesity (2005) 21 23917806
1986 Purification and characterization of a molybdenum-pterin-binding protein (Mop) in Clostridium pasteurianum W5. Journal of bacteriology 21 3782020
2018 Nociceptin/orphanin FQ opioid peptide (NOP) receptor and µ-opioid peptide (MOP) receptors both contribute to the anti-hypersensitive effect of cebranopadol in a rat model of arthritic pain. European journal of pharmacology 20 29753041
2017 Buprenorphine requires concomitant activation of NOP and MOP receptors to reduce cocaine consumption. Addiction biology 20 28635181
2001 Plant microtubule-associated proteins: the HEAT is off in temperature-sensitive mor1. Trends in plant science 20 11544108
1983 Induction of SCE by DNA cross-links in human fibroblasts exposed to 8-MOP and UVA irradiation. Mutation research 20 6877268
2022 MOR1/MAP215 acts synergistically with katanin to control cell division and anisotropic cell elongation in Arabidopsis. The Plant cell 19 35579372
2019 Influences of COMT rs4680 and OPRM1 rs1799971 Polymorphisms on Chronic Postsurgical Pain, Acute Pain, and Analgesic Consumption After Elective Cesarean Delivery. The Clinical journal of pain 19 30234521
2018 The OPRM1 A118G polymorphism: converging evidence against associations with alcohol sensitivity and consumption. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 18 29497164
2014 Cellular signalling of non-synonymous single-nucleotide polymorphisms of the human μ-opioid receptor (OPRM1). British journal of pharmacology 18 24527749
2012 The N-terminal TOG domain of Arabidopsis MOR1 modulates affinity for microtubule polymers. Journal of cell science 18 22825869
2011 Functional polymorphism of the mu-opioid receptor gene (OPRM1) influences reinforcement learning in humans. PloS one 18 21912675
2009 Differential use of an in-frame translation initiation codon regulates human mu opioid receptor (OPRM1). Cellular and molecular life sciences : CMLS 18 19609488
1977 Induction of multinucleate cells by 8-MOP and UV treatment in vitro and in vivo. Dermatologica 18 892116
2017 Mu-opioid peptide (MOP) and nociceptin/orphanin FQ peptide (NOP) receptor activation both contribute to the discriminative stimulus properties of cebranopadol in the rat. Neuropharmacology 17 29155273
2015 Prenatal exposure to cigarette smoke interacts with OPRM1 to modulate dietary preference for fat. Journal of psychiatry & neuroscience : JPN 17 25266401
2015 Influence of UGT2B7, CYP3A4, and OPRM1 Gene Polymorphisms on Transdermal Buprenorphine Pain Control in Patients with Critical Lower Limb Ischemia Awaiting Revascularization. Pain practice : the official journal of World Institute of Pain 17 26407542
2013 Effects of OPRM1 A118G polymorphism on epidural analgesia with fentanyl during labor: a meta-analysis. Genetic testing and molecular biomarkers 17 23909491