Affinage

OPRM1

Mu-type opioid receptor · UniProt P35372

Length
400 aa
Mass
44.8 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OPRM1 encodes the mu-opioid receptor (MOR1), a G protein-coupled receptor that is preferentially targeted to the somatodendritic domain of most neurons, with discrete axonal targeting in some primary afferent populations (PMID:7751913), and which couples agonist binding to G protein activation and adenylate cyclase regulation (PMID:9466465). The gene undergoes extensive alternative splicing of both N-terminal and C-terminal exons, generating pharmacologically distinct isoforms: N-terminal variants alter G protein coupling efficiency (PMID:21255438) while full-length 7TM C-terminal variants display agonist- and isoform-dependent biases in G protein versus β-arrestin2 signaling, with exon 7-associated MOR-1O showing greater β-arrestin2 bias than exon 4-associated MOR-1 (PMID:33033993). OPRM1 expression is tightly controlled at multiple post-transcriptional and epigenetic levels: miRNA23b binds a K box motif in the 3'-UTR to block polysome association and translation, a repression that is amplified by chronic morphine (PMID:18716031, PMID:19144786), while in sensory neurons MBD1/DNMT3a and MeCP2/HDAC1 are recruited to the Oprm1 promoter to silence transcription under pain conditions (PMID:30266739, PMID:34803588). Functionally, MOR signaling governs antinociception, opioid reward, and social behavior through defined circuits — it shapes excitatory/inhibitory balance and firing of VTA dopaminergic neurons (PMID:31109961) and regulates inhibitory synaptic input onto nucleus accumbens MSNs, with NAc MOR-expressing neurons playing a cell-type-specific, sex-differentiated role in opioid self-administration (PMID:34301826, PMID:36717230). The common A118G (N40D) variant reduces OPRM1 mRNA and protein via a transcription/mRNA maturation defect (PMID:16046395) and lowers receptor availability in human brain (PMID:21576462). Activation of OPRM1 can also drive IP3R-mediated ER Ca2+ release and a calpain-1–Bid–cytochrome C–caspase apoptotic cascade in leukemic cells (PMID:33441856).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 Medium

    Establishing where MOR1 protein resides and which neurons express it was needed to map opioid action; immunolocalization showed somatodendritic targeting with discrete axonal targeting, and that spinal MOR1+ neurons are predominantly excitatory interneurons.

    Evidence Immunohistochemistry with C-terminal antisera, MAP2 double-labeling, and GABA/glycine co-labeling in rat brain and spinal cord

    PMID:7751913 PMID:8938756

    Open questions at the time
    • Single-lab antisera-based localization
    • Functional consequence of differential targeting not tested
    • Human distribution not directly addressed
  2. 1998 Medium

    Whether splice isoforms differ functionally was unknown; rMOR1 versus rMOR1B showed similar binding but distinct agonist-induced desensitization and differential anatomical distribution, establishing isoform-specific pharmacology.

    Evidence Isoform-specific antibodies, immunocytochemistry, and adenylate cyclase desensitization assays in rat

    PMID:9466465

    Open questions at the time
    • Mechanism of differential desensitization not resolved
    • Single lab
    • Human isoform relevance untested
  3. 2005 High

    The molecular basis of the A118G (N40D) functional effect was unclear; allelic expression showed the G allele reduces mRNA ~1.5-fold and protein >10-fold via a transcription/mRNA maturation defect rather than altered stability.

    Evidence Allele-specific expression in human autopsy brain and CHO cells, Western blot, binding, and actinomycin D stability assay

    PMID:16046395

    Open questions at the time
    • Exact transcription/maturation step affected not pinpointed
    • Heterologous cell context
    • Disconnect between mRNA and protein magnitude unexplained
  4. 2009 High

    How MOR1 protein is post-transcriptionally tuned was unknown; miRNA23b was shown to bind a 3'-UTR K box and block polysome association, and chronic morphine was shown to upregulate miRNA23b, linking opioid exposure to translational downregulation.

    Evidence 3'-UTR reporter assays, polysome fractionation, miRNA23b knockdown in NS20Y cells, and dose/time morphine treatment

    PMID:18716031 PMID:19144786

    Open questions at the time
    • In vivo physiological role of miRNA23b not established
    • Cell line context
    • Link to behavioral tolerance not tested
  5. 2009 High

    Whether the A118G effect translates to organismal opioid responses was untested; an A112G knock-in mouse recapitulated reduced mRNA/protein and showed reduced morphine antinociception, sensitization, and sex-specific reward/withdrawal changes.

    Evidence A112G knock-in mouse, binding, Western blot, and behavioral pharmacology

    PMID:19528658

    Open questions at the time
    • Circuit basis of behavioral changes not resolved here
    • Sex-difference mechanism unknown
  6. 2011 Medium

    Whether the A118G effect alters receptor availability in living human brain was unknown; PET imaging showed AA homozygotes have higher mu-receptor binding potential in amygdala, thalamus, and anterior cingulate than G carriers.

    Evidence [11C]carfentanil PET in genotyped human smokers

    PMID:21576462

    Open questions at the time
    • Smoker-only cohort
    • Single radioligand method
    • Causal link to behavior not established
  7. 2011 Medium

    Whether N-terminal sequence influences signaling was open; the exon 11-associated variant rMOR-1H2 with an extended N-terminus altered agonist-induced G protein activation without changing binding, showing the N-terminus tunes coupling efficiency.

    Evidence RT-PCR variant identification and CHO-cell G protein activation and binding assays

    PMID:21255438

    Open questions at the time
    • In vivo expression and role of rMOR-1H2 unknown
    • Single heterologous system
  8. 2018 High

    How Oprm1 is transcriptionally silenced in pain states was unknown; MBD1 was shown to recruit DNMT3a to the Oprm1 promoter in DRG neurons, with MBD1 loss/gain bidirectionally controlling pain sensitivity.

    Evidence MBD1 knockout and DRG overexpression mice, DNMT3a recruitment assay, and pain behavior

    PMID:30266739

    Open questions at the time
    • Trigger for MBD1 promoter recruitment unclear
    • Whether MOR is the sole MBD1 target mediating pain not resolved
  9. 2021 High

    A second epigenetic silencing route in injured sensory neurons was defined; MeCP2 recruits HDAC1 to hypermethylated Oprm1 promoter regions, reducing H3 acetylation and MOR expression, with knockdown restoring MOR and morphine analgesia.

    Evidence MeCP2 knockdown/overexpression, HDAC inhibition, chromatin assays, qPCR, Western blot, and morphine analgesia testing

    PMID:34803588

    Open questions at the time
    • Interplay between MBD1/DNMT3a and MeCP2/HDAC1 routes not integrated
    • Human relevance untested
  10. 2020 Medium

    Whether C-terminal splice variants differ in signaling bias was open; full-length 7TM variants showed agonist- and isoform-dependent G protein versus β-arrestin2 recruitment, with MOR-1O more β-arrestin2-biased than MOR-1.

    Evidence Cell-based G protein activation and β-arrestin2 recruitment assays across multiple variants and agonists

    PMID:33033993

    Open questions at the time
    • In vivo consequences of variant-specific bias not shown
    • Single lab heterologous assays
  11. 2019 High

    The circuit mechanism by which A118G alters reward was unknown; in A112G mice MOR agonists shifted E/I balance and firing of NAc-projecting VTA dopamine neurons, with G/G mice showing blunted sensitivity and presynaptic GABAB-mediated mEPSC facilitation predominant in A/A mice.

    Evidence Electrophysiology (mIPSC, mEPSC, firing) in VTA dopamine neurons from A112G knock-in mice with pharmacological dissection

    PMID:31109961

    Open questions at the time
    • Behavioral linkage of the firing shift not directly demonstrated here
    • Mechanism of GABAB recruitment differences unclear
  12. 2021 High

    How OPRM1 shapes social reward circuitry was unresolved; heterozygous Oprm1 knockout selectively increased inhibitory transmission and gephyrin/synaptic puncta at NAc D2-MSNs, accompanied by social reward and interaction deficits.

    Evidence Oprm1 knockout mice, D1/D2-MSN electrophysiology, gephyrin RNAscope, synaptic immunofluorescence, and social behavior assays

    PMID:34301826

    Open questions at the time
    • Cell-autonomous versus circuit origin of synaptic change not separated
    • Sex difference in electrophysiology mechanism unknown
  13. 2015 High

    Whether NAc MOR+ neurons are causally required for opioid reinforcement was untested; Cre-dependent caspase ablation of NAc MOR+ cells in Oprm1-Cre rats reduced heroin self-administration acquisition in males and effort in females, establishing a sex-differentiated cell-type-specific role.

    Evidence Oprm1-Cre knock-in rat, AAV-caspase lesion, heroin self-administration, and HCR-FISH validation

    PMID:36717230

    Open questions at the time
    • Identity of the relevant NAc MOR+ neuron subtypes not fully defined
    • Mechanism of sex difference unresolved
  14. 2018 Medium

    OPRM1 was placed in social-behavior and addiction genetic networks; it acts as a downstream effector of MeCP2 overexpression mediating social deficits, its A112G G allele confers social resilience via naloxone-sensitive endogenous opioid tone, and it interacts epistatically with Taar1 to set methamphetamine intake.

    Evidence MECP2 duplication mouse epistasis, A112G knock-in social/defeat assays with naloxone and c-fos mapping, and recombinant inbred Taar1×Oprm1 interval mapping

    PMID:22231481 PMID:25716856 PMID:31274109

    Open questions at the time
    • Molecular basis of Oprm1-Taar1 epistasis unknown
    • Human translation of social-resilience phenotype untested
  15. 2019 High

    A non-neuronal pro-apoptotic role and an additional regulatory miRNA were identified; OPRM1 activation by D,L-methadone triggers an IP3R/Ca2+–calpain-1–Bid–cytochrome C–caspase cascade in leukemic cells, and tumor-derived exosomal let-7d-5p directly suppresses OPRM1 in DRG neurons to drive cancer pain.

    Evidence OPRM1 loss-of-function, Ca2+ imaging, BAPTA-AM rescue and apoptotic-marker assays in leukemic cells; exosomal let-7d-5p uptake, target validation, and bone-pain model

    PMID:33441856 PMID:34124049

    Open questions at the time
    • Generality of the apoptotic pathway beyond leukemic cells unknown
    • Endogenous physiological relevance of methadone-driven Ca2+ pathway unclear
  16. 2023 Medium

    Tools for cell-type-specific access to MOR+ neurons were lacking; MOR promoter-based AAV constructs drove selective expression in endogenous MOR+ neurons across mouse, rat, shrew, iPSC-derived nociceptors, and macaque, enabling targeted manipulation of mu-opioidergic cells.

    Evidence AAV MOR-promoter constructs with fiber photometry, DREADD chemogenetics, and cross-species validation

    PMID:37704594

    Open questions at the time
    • Promoter fidelity relative to full endogenous OPRM1 expression incomplete
    • Long-term and clinical applicability not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory layers — alternative splicing, miRNA repression, and competing MBD1/DNMT3a versus MeCP2/HDAC1 epigenetic silencing — are integrated to set MOR levels in specific neuron types and circuits, and how A118G acts mechanistically at the transcription/maturation step, remain unresolved.
  • No unified model linking splice-variant bias to circuit-specific behavior
  • Exact molecular lesion of A118G undefined
  • Cross-talk among regulatory layers unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-5357801 Programmed Cell Death 1
Partners
ARRB2DNMT3AFLNAHDAC1MBD1MECP2

Evidence

Reading pass · 22 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 in most neurons, but discrete neuronal populations (including some primary afferent neurons co-expressing DOR1) target MOR1 to axons, as determined by double-labeling with MAP2 and immunohistochemistry in brain and spinal cord. Immunohistochemistry with anti-C-terminal peptide antisera, Western blot, immunoisolation, double-labeling with MAP2 The Journal of neuroscience Medium 7751913
1998 Alternative splicing of the rat OPRM1 gene generates two isoforms, rMOR1 and rMOR1B, which exhibit similar pharmacological profiles but differ in agonist-induced desensitization of coupling to adenylate cyclase. MOR1B is predominantly localized to the olfactory bulb (external plexiform layer/mitral cell dendrites), while MOR1 is broadly distributed in pain-controlling brain areas including spinal cord dorsal horn, raphe nuclei, and periaqueductal gray. Isoform-specific polyclonal antibodies, immunocytochemistry, adenylate cyclase desensitization assays Neuroscience Medium 9466465
1996 In the superficial dorsal horn of the rat spinal cord, MOR1 immunoreactivity is present on cell bodies and dendrites of neurons in lamina II-III, and 94% of MOR1-immunoreactive neurons are neither GABA- nor glycine-immunoreactive, indicating they are predominantly excitatory interneurons rather than inhibitory neurons. Pre-embedding immunocytochemistry for MOR1 combined with post-embedding immunolabeling for GABA and glycine Neuroscience Medium 8938756
2005 The OPRM1 A118G SNP (N40D substitution) reduces OPRM1 mRNA levels approximately 1.5-fold and reduces protein levels more than 10-fold compared to the A118 allele when expressed in CHO cells; this effect is due to a defect in transcription or mRNA maturation rather than altered mRNA stability, as mRNA turnover after actinomycin D treatment is not different between alleles. Allele-specific mRNA expression in human autopsy brain tissue, CHO cell transfection with allelic cDNA constructs, Western blot, receptor binding assay, actinomycin D mRNA stability assay The Journal of biological chemistry High 16046395
2008 miRNA23b suppresses MOR1 (OPRM1) protein expression by interacting with a K box motif in the 3'-UTR of MOR1 mRNA and blocking its association with polysomes, thereby inhibiting translation; knockdown of endogenous miRNA23b in NS20Y cells increases MOR1 protein expression. 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 through the MOR1 3'-UTR, linking chronic morphine exposure to post-transcriptional downregulation of MOR1 protein. Dose-response morphine treatment, polysome-mRNA association assay, translational luciferase reporter assay with MOR1 3'-UTR Molecular pharmacology High 19144786
2009 A mouse model carrying the equivalent of the human OPRM1 A118G SNP (A112G in mice) shows reduced Oprm1 mRNA expression and reduced receptor protein levels, along with reduced morphine-mediated antinociception, reduced morphine-mediated hyperactivity, and reduced locomotor sensitization; sex-specific reductions in morphine reward and naloxone-precipitated withdrawal aversion were also observed. Knock-in mouse model with A112G nucleotide substitution, receptor binding assay, Western blot, behavioral pharmacology (antinociception, locomotor activity, conditioned place preference, naloxone-precipitated withdrawal) Proceedings of the National Academy of Sciences High 19528658
2011 In vivo PET imaging with [11C]carfentanil shows that smokers homozygous for the wild-type OPRM1 A allele have significantly higher mu-opioid receptor binding potential (receptor availability) in bilateral amygdala, left thalamus, and left anterior cingulate cortex compared to G allele carriers, demonstrating that the A118G SNP affects in vivo receptor levels in human brain. [11C]carfentanil PET imaging in genotyped human smokers Proceedings of the National Academy of Sciences Medium 21576462
2011 Seven new exon 11-associated splice variants of rat OPRM1 were identified; one novel variant, rMOR-1H2, contains an additional 50 amino acids at the N-terminus and when expressed in CHO cells significantly alters agonist-induced G protein activation with little effect on opioid binding, indicating the N-terminal sequence influences G protein coupling efficiency. RT-PCR splice variant identification, CHO cell expression, G protein activation assay, opioid binding assay Molecular pain Medium 21255438
2018 MBD1 (methyl-CpG-binding domain protein 1) in DRG primary sensory neurons represses Oprm1 gene expression by recruiting DNA methyltransferase DNMT3a to the Oprm1 promoter; MBD1-deficient mice show reduced acute pain responses and blunted neuropathic pain, while DRG overexpression of MBD1 produces pain hypersensitivity and rescues acute pain sensitivity in MBD1-deficient mice. MBD1 knockout mice, DRG-specific overexpression via viral vector, ChIP-style recruitment assay of DNMT3a to Oprm1 promoter, behavioral pain testing The Journal of neuroscience High 30266739
2020 mu-Opioid agonists produce markedly different levels of G protein activation and β-arrestin2 recruitment among the full-length 7TM C-terminal splice variants of Oprm1 (e.g., MOR-1 vs. MOR-1O), leading to biased signaling that varies by both agonist and splice variant; MOR-1O (exon 7-associated) shows greater β-arrestin2 bias than MOR-1 (exon 4-associated) for most mu agonists. Cell-based G protein activation assay and β-arrestin2 recruitment assay for multiple C-terminal splice variants expressed in vitro Cellular and molecular neurobiology Medium 33033993
2021 MeCP2 in injured DRG neurons is upregulated after nerve injury, recruits HDAC1 to hypermethylated regions of the Oprm1 promoter, reduces histone H3 acetylation at the Oprm1 promoter, and thereby suppresses Oprm1 transcription and reduces MOR expression; MeCP2 knockdown restores MOR expression in injured DRG and enhances morphine analgesia, while HDAC1 inhibition prevents MOR reduction. MeCP2 knockdown (intrathecal viral vector), MeCP2 overexpression (viral vector), HDAC inhibitor (suberoylanilide hydroxamic acid) treatment, ChIP-like assay for HDAC1 binding and histone acetylation at Oprm1 promoter, qPCR, Western blot, behavioral morphine analgesia testing Frontiers in neuroscience High 34803588
2019 OPRM1 activation by D,L-methadone in leukemic cells triggers IP3R-mediated ER Ca2+ release and reduces the rate of Ca2+ efflux, causing a lethal rise in intracellular [Ca2+] that activates the calpain-1–Bid–cytochrome C–caspase-3/12 apoptotic pathway; OPRM1 loss blocks all these effects and prevents D,L-methadone-induced apoptosis, while BAPTA-AM chelation of intracellular Ca2+ also reverses apoptosis. OPRM1 knockdown/loss experiments, Ca2+ imaging (ER release and efflux), BAPTA-AM chelation, caspase-3/12 activation assay, cytochrome C release, Western blot for Bid truncation and calpain-1 activation Scientific reports High 33441856
2021 Heterozygous genetic knockout of Oprm1 in mice increases inhibitory synaptic transmission specifically in D2-MSNs of the nucleus accumbens (males only) and increases gephyrin mRNA and inhibitory synaptic puncta density at D2-MSN cell bodies (both sexes); these synaptic changes are associated with deficits in social conditioned place preference and reciprocal social interaction, placing OPRM1 signaling in NAc microcircuitry as a regulator of social reward behavior. Heterozygous and homozygous Oprm1 knockout mice, electrophysiology (inhibitory synaptic transmission in D2-MSNs vs D1-MSNs), RNAscope for gephyrin mRNA, immunofluorescence for synaptic puncta, social conditioned place preference and reciprocal social interaction behavioral assays The Journal of neuroscience High 34301826
2019 In a mouse model of OPRM1 A112G, MOR agonists (DAMGO and morphine) suppress both inhibitory and excitatory inputs to VTA dopaminergic neurons projecting to NAc medial shell, causing a shift in E/I balance and increased action potential firing; G/G allele mice show lower sensitivity to these effects, and DAMGO produces facilitatory effects on mEPSCs via presynaptic GABAB receptors predominantly in A/A mice, contributing to stronger dopamine neuron firing shifts in A/A mice. Electrophysiology (mIPSC, mEPSC, action potential firing) in VTA dopaminergic neurons from A112G knock-in mice, pharmacological dissection with DAMGO, morphine, GABAB receptor manipulation The Journal of neuroscience High 31109961
2012 In MECP2 duplication mice with heightened anxiety and autism-like features, reducing Oprm1 expression (but not CRH/CRHR1 reduction) specifically improved abnormal social behavior, establishing Oprm1 as a downstream effector of MeCP2 overexpression that mediates social behavior deficits. Genetic epistasis in MECP2 duplication mice with reduced Oprm1 expression, behavioral assays for anxiety and social behavior Nature genetics Medium 22231481
2021 Lung cancer cell-derived exosomal let-7d-5p is taken up by DRG neurons and directly inhibits OPRM1 protein levels via targeting of the OPRM1 mRNA; this suppression of OPRM1 in DRG neurons contributes to cancer-induced bone pain generation and maintenance in vivo. Exosome isolation, uptake assay in DRG neurons, let-7d-5p overexpression/inhibition, OPRM1 protein measurement (Western blot), mouse cancer-induced bone pain model with exosome injection Frontiers in cell and developmental biology Medium 34124049
2015 Selective lesioning of nucleus accumbens MOR-expressing cells (using Cre-dependent caspase in Oprm1-Cre knock-in rats) decreased acquisition of heroin self-administration in males and had a stronger inhibitory effect on effort to self-administer heroin in females, establishing a cell-type-specific and sex-differentiated role for NAc OPRM1-expressing neurons in opioid reinforcement. CRISPR-based Oprm1-Cre knock-in rat, Cre-dependent AAV-caspase lesion of NAc MOR+ cells, heroin self-administration behavioral testing in male and female rats, HCR-FISH for Oprm1/iCre co-expression validation The Journal of neuroscience High 36717230
2015 In the OPRM1 A112G mouse model, G allele carriers show increased home-cage dominance, increased motivation for social interaction, and resilience to social defeat with lack of subsequent social avoidance and reduced anhedonia; resilience is associated with greater c-fos induction in NAc and PAG, and the increase in social affiliation in G carriers is blocked by naloxone, indicating altered endogenous opioid tone mediates the social phenotype. A112G knock-in mice, social preference and dominance assays, social defeat paradigm, intracranial self-stimulation for anhedonia, c-fos immunohistochemistry, naloxone pharmacological blockade The Journal of neuroscience High 25716856
2019 Taar1 and Oprm1 genotypes interact epistatically to regulate methamphetamine intake and thermal response to methamphetamine in mice; the independent effect of Taar1 on methamphetamine intake was dependent on genotype at Oprm1, as shown by interval mapping in recombinant inbred strains. Selective breeding, CRISPR-Cas9 Taar1 editing, recombinant inbred strain interval mapping, methamphetamine self-administration and thermal response assays, genetic epistasis analysis eLife Medium 31274109
2014 Differential expression of the N-terminal OPRM1 splice variant MOR-1K (a single-TM variant mediating excitatory signaling) is observed in HIV-infected individuals with neurocognitive impairment and HIV encephalitis; overexpression of filamin A (FLNA), a network-identified interaction partner of MOR-1K, redistributes MOR-1K from intracellular compartments to the cell surface in HEK293 cells. RT-PCR for MOR-1K splice variant, network analysis of microarray data, FLNA overexpression in HEK293 cells with MOR-1K localization assessment AIDS Low 24413261
2023 MOR promoter (MORp)-based AAV constructs (derived from mouse Oprm1 upstream promoter regions) drive transgene expression selectively in endogenous MOR+ neurons in mouse brain, spinal cord, and periphery, and are functional in rats, shrews, and human iPSC-derived nociceptors; a human MORp efficiently transduced macaque cortical OPRM1+ cells, validating these constructs for cell-type-specific genetic access to mu-opioidergic neurons. AAV-delivered MOR promoter constructs, fiber photometry, chemogenetics (DREADDs), intersectional genetics, validation in multiple species including iPSC-derived nociceptors and macaque Nature communications Medium 37704594

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 452 16046395
2001 MOR1 is essential for organizing cortical microtubules in plants. Nature 323 11385579
2021 Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clinical pharmacology and therapeutics 316 33387367
2007 Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief. Clinical pharmacology and therapeutics 245 17898703
2002 MOR1/GEM1 has an essential role in the plant-specific cytokinetic phragmoplast. Nature cell biology 162 12198497
2013 Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome. JAMA 149 23632726
2009 Meta-analysis of the relevance of the OPRM1 118A>G genetic variant for pain treatment. Pain 146 19683391
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
2006 Association between two mu-opioid receptor gene (OPRM1) haplotype blocks and drug or alcohol dependence. Human molecular genetics 131 16476706
2008 Increased OPRM1 DNA methylation in lymphocytes of methadone-maintained former heroin addicts. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 128 18650805
2012 Association of µ-opioid receptor (OPRM1) gene polymorphism with response to naltrexone in alcohol dependence: a systematic review and meta-analysis. Addiction biology 121 22515274
2012 Crh and Oprm1 mediate anxiety-related behavior and social approach in a mouse model of MECP2 duplication syndrome. Nature genetics 117 22231481
2010 OPRM1 SNP (A118G): involvement in disease development, treatment response, and animal models. Drug and alcohol dependence 115 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 112 15731588
2014 OPRM1 A118G gene variant and postoperative opioid requirement: a systematic review and meta-analysis. Anesthesiology 110 25102313
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
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
2001 Nonreplication of association between mu-opioid-receptor gene (OPRM1) A118G polymorphism and substance dependence. American journal of medical genetics 94 11424981
2011 Elevated levels of DNA methylation at the OPRM1 promoter in blood and sperm from male opioid addicts. Journal of opioid management 93 21957825
2013 Pharmacogenetics of OPRM1. Pharmacology, biochemistry, and behavior 78 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 72 19144786
2013 OPRM1 rs1799971 polymorphism and opioid dependence: evidence from a meta-analysis. Pharmacogenomics 69 23651028
2012 Ethnicity interacts with the OPRM1 gene in experimental pain sensitivity. Pain 68 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
2015 Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1. Biological psychiatry 54 25744370
2011 Mu-opioid receptor (OPRM1) variation, oxytocin levels and maternal attachment in free-ranging rhesus macaques Macaca mulatta. Behavioral neuroscience 54 21463018
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 51 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 49 23703421
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 49 18716031
2016 OPRM1 and COMT Gene-Gene Interaction Is Associated With Postoperative Pain and Opioid Consumption After Orthopedic Trauma. Biological research for nursing 47 27903758
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
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
2009 Polymorphism of the micro-opioid receptor gene (OPRM1 118A>G) affects fentanyl-induced analgesia during anesthesia and recovery. Molecular diagnosis & therapy 43 19791836
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
2019 OPRM1 rs1799971, COMT rs4680, and FAAH rs324420 genes interact with placebo procedures to induce hypoalgesia. Pain 39 31335650
2020 Effect of short-term prescription opioids on DNA methylation of the OPRM1 promoter. Clinical epigenetics 38 32493461
2018 Epigenetic variation in OPRM1 gene in opioid-exposed mother-infant dyads. Genes, brain, and behavior 38 29575474
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
2018 Suggestive association between OPRM1 and impulse control disorders in Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society 35 30444952
2011 Identification and characterization of seven new exon 11-associated splice variants of the rat μ opioid receptor gene, OPRM1. Molecular pain 35 21255438
2010 OPRM1 gene variants modulate amphetamine-induced euphoria in humans. Genes, brain, and behavior 35 21029375
2013 µ-opioid receptor gene variant OPRM1 118 A>G: a summary of its molecular and clinical consequences for pain. Pharmacogenomics 33 24236490
2007 Identification of five mouse mu-opioid receptor (MOR) gene (Oprm1) splice variants containing a newly identified alternatively spliced exon. Gene 32 17398041
2017 OPRM1 Methylation Contributes to Opioid Tolerance in Cancer Patients. The journal of pain 31 28456745
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
2013 μ-Opioid receptor gene (OPRM1) polymorphism A118G: lack of association in Finnish populations with alcohol dependence or alcohol consumption. Alcohol and alcoholism (Oxford, Oxfordshire) 28 23729673
2020 Systematic review and meta-analysis of the moderating effect of rs1799971 in OPRM1, the mu-opioid receptor gene, on response to naltrexone treatment of alcohol use disorder. Addiction (Abingdon, England) 27 31961981
2018 Elevated methylation of OPRM1 and OPRL1 genes in Alzheimer's disease. Molecular medicine reports 27 30152845
2014 MOR1 expression in gastric cancer: a biomarker associated with poor outcome. Clinical and translational science 27 25441763
2006 Identification of three mouse mu-opioid receptor (MOR) gene (Oprm1) splice variants containing a newly identified alternatively spliced exon. Gene 27 17156941
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
2021 MeCP2 Epigenetic Silencing of Oprm1 Gene in Primary Sensory Neurons Under Neuropathic Pain Conditions. Frontiers in neuroscience 24 34803588
2020 Mu Opioid Receptor 1 (MOR-1) Expression in Colorectal Cancer and Oncological Long-Term Outcomes: A Five-Year Retrospective Longitudinal Cohort Study. Cancers 24 31948099
2019 Taar1 gene variants have a causal role in methamphetamine intake and response and interact with Oprm1. eLife 24 31274109
2018 Fundamental Considerations for Genetically-Guided Pain Management with Opioids Based on CYP2D6 and OPRM1 Polymorphisms. Pain physician 24 30508992
2014 Association of μ-opioid receptor gene (OPRM1) haplotypes with postoperative nausea and vomiting. Experimental brain research 24 24858579
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
2020 Dysregulated expression of the alternatively spliced variant mRNAs of the mu opioid receptor gene, OPRM1, in the medial prefrontal cortex of male human heroin abusers and heroin self-administering male rats. Journal of neuroscience research 23 32506472
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
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
2007 Polymorphisms in the mu-opioid receptor gene (OPRM1) and the implications for alcohol dependence in humans. Pharmacogenomics 22 17979515
2020 OPRM1 and COMT polymorphisms: implications on postoperative acute, chronic and experimental pain after cardiac surgery. Pharmacogenomics 21 31967515
2013 Lack of association between DRD2 and OPRM1 genotypes and adiposity. International journal of obesity (2005) 21 23917806
2020 Mu Opioids Induce Biased Signaling at the Full-Length Seven Transmembrane C-Terminal Splice Variants of the mu Opioid Receptor Gene, Oprm1. Cellular and molecular neurobiology 20 33033993
2001 Plant microtubule-associated proteins: the HEAT is off in temperature-sensitive mor1. Trends in plant science 20 11544108
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
2019 Effects of OPRM1 and ABCB1 gene polymorphisms on the analgesic effect and dose of sufentanil after thoracoscopic-assisted radical resection of lung cancer. Bioscience reports 18 30455395
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
2018 Opioid receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) and postoperative nausea and vomiting. American journal of translational research 18 30323865
2014 Cellular signalling of non-synonymous single-nucleotide polymorphisms of the human μ-opioid receptor (OPRM1). British journal of pharmacology 18 24527749
2023 Effect of Selective Lesions of Nucleus Accumbens µ-Opioid Receptor-Expressing Cells on Heroin Self-Administration in Male and Female Rats: A Study with Novel Oprm1-Cre Knock-in Rats. The Journal of neuroscience : the official journal of the Society for Neuroscience 17 36717230
2019 Synaptic Regulation by OPRM1 Variants in Reward Neurocircuitry. The Journal of neuroscience : the official journal of the Society for Neuroscience 17 31109961
2013 Effects of OPRM1 A118G polymorphism on epidural analgesia with fentanyl during labor: a meta-analysis. Genetic testing and molecular biomarkers 17 23909491
2018 Methadone Dosage and Plasma Levels, SNPs of OPRM1 Gene and Age of First Drug Use Were Associated With Outcomes of Methadone Maintenance Treatment. Frontiers in genetics 16 30420869
2016 COMT and OPRM1 Genotype Associations with Daily Knee Pain Variability and Activity Induced Pain. Scandinavian journal of pain 16 26322144
2014 OPRM1 receptor as new biomarker to help the prediction of post mastectomy pain and recurrence in breast cancer. Minerva anestesiologica 16 25300626
2021 D,L-Methadone causes leukemic cell apoptosis via an OPRM1-triggered increase in IP3R-mediated ER Ca2+ release and decrease in Ca2+ efflux, elevating [Ca2+]i. Scientific reports 15 33441856
2019 OPRM1 Gene Interaction with Sleep in Chronic Pain Patients Treated with Opioids. Pain physician 15 30700073
2008 OPRM1 gene is associated with BMI in Uyghur population. Obesity (Silver Spring, Md.) 15 19008867
2005 Novel exonic mu-opioid receptor gene (OPRM1) polymorphisms not associated with opioid dependence. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 15 15558714
2022 The OPRM1 gene and interactions with the 5-HT1a gene regulate conditioned pain modulation in fibromyalgia patients and healthy controls. PloS one 14 36342939
2019 Variation in the μ-opioid receptor gene (OPRM1) and experiences of felt security in response to a romantic partner's quarrelsome behavior. Molecular psychiatry 14 31772303
2017 Lack of associations of the opioid receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) with alcohol dependence: review and meta-analysis of retrospective controlled studies. BMC medical genetics 14 29070014
2022 Anatomical Analysis of Transient Potential Vanilloid Receptor 1 (Trpv1+) and Mu-Opioid Receptor (Oprm1+) Co-expression in Rat Dorsal Root Ganglion Neurons. Frontiers in molecular neuroscience 13 35875671
2018 The impact of OPRM1's genetic polymorphisms on methadone maintenance treatment in opioid addicts: a systematic review. Pharmacogenomics 13 29785888

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