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FLASH GENE
Symbol OPRM1 contributors: mct/npt - updated : 12-10-2015
HGNC name opioid receptor, mu 1
HGNC id 8156
Location 6q25.2      Physical location : 154.331.635 - 154.568.001
Synonym name
  • mu-type opioid receptor
  • mu opiate receptor
  • Synonym symbol(s) D6S1836, MOR1, OPRM, KIAA0403, MOR, LMOR, MOR-1, MOPr
    DNA
    TYPE functioning gene
    STRUCTURE 236.37 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   silencer
    text structure
  • neurorestrictive suppressor element (NRSE), functioning as a critical regulator to repress the OPRM1 gene expression in specific neuronal cells depending on REST expression level
  • proximal promoter with negative and negative cis-acting element
  • in the 3'UTR, 33 AU-rich regions and more than 300 putative transcription factor-binding sites, affecting gene expression, and implicated in the sensitivity to opioids
  • the proximal promoter region was unmethylated in differentiated cells compared to its hypermethylation in undifferentiated cells (Hwang 2007)
  • polymorphic polypyrimidine/polypurine (PPy/u) motif, a key enhancer of OPRM1 gene expression
  • MAPPING cloned Y linked N status confirmed
    Physical map
    ULBP2 6q25 UL16 binding protein 2 ULBP1 6q25 UL16 binding protein 1 LOC345829 6q24.3 similar to Transcription factor BTF3 (RNA polymerase B transcription factor 3) LOC391980 6 similar to UL16 binding protein 1; alcan-beta RAET1L 6q25 retinoic acid early transcript 1L PHBP1 6q25 prohibitin pseudogene 1 ULBP3 6q25 UL16 binding protein 3 PPP1R14C 6q24.3-q25.3 protein phosphatase 1, regulatory (inhibitor) subunit 14C RNU4P1 6q25.1 RNA, U4 small nuclear pseudogene 1 (U4/7) LOC389434 6 similar to iodotyrosine dehalogenase protein PLEKHG1 6q25.1 pleckstrin homology domain containing, family G (with RhoGef domain) member 1 FTHFSDC1 6q25.1 formyltetrahydrofolate synthetase domain containing 1 LOC391982 6 similar to ribosomal protein S12 AKAP12 6q24-q25 a kinase (PRKA) anchor protein (gravin) 12 ZBTB2 6q25.1 zinc finger and BTB domain containing 2 C6orf96 6q25.1 chromosome 6 open reading frame 96 C6orf211 6q25.1 chromosome 6 open reading frame 211 C6orf97 6q25.1 chromosome 6 open reading frame 97 ESR1 6q25.1 estrogen receptor 1 SYNE1 6q25 spectrin repeat containing, nuclear envelope 1 MYCT1 6q25.1 myc target 1 VIP 6q24-q27 vasoactive intestinal peptide LOC391983 6 similar to Tubulin beta-2 chain FBXO5 6q25-q26 F-box only protein 5 MTRF1L 6q25-q26 mitochondrial translational release factor 1-like RGS17 6q25-q26 regulator of G-protein signalling 17 LOC389435 6 similar to 60S ribosomal protein L27a OPRM1 6q24-q25 opioid receptor, mu 1 PIP3-E 6q25.2 phosphoinositide-binding protein PIP3-E MAGI1 6q25.2 membrane associated guanylate kinase interacting protein-like 1 LOC391984 6 similar to stathmin-like 2; superiorcervical ganglia, neural specific 10 RBM16 6q25.1-q25.3 RNA binding motif protein 16 LOC389436 6 LOC389436 TFB1M 6q25.1-q25.3 transcription factor B1, mitochondrial NOX3 6q25.1-26 NADPH oxidase 3 LOC389437 6 LOC389437 ELD/OSA1 6q25.1 LOC389437 ZDHHC14 6q25.3 zinc finger, DHHC domain containing 14 LOC389438 6 LOC389438 SNX9 6q25.1-q26 sorting nexin 9 SYNJ2 6q25.1-q25.2 synaptojanin 2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 1867 - 392 - 2003 12734358
    also called MOR-1A
    - - 2949 - 300 - 2003 12734358
    also called MOR-1K1
    4 - 1710 - 319 - 2003 12734358
    also called MOR-1G2
    4 - 2178 - 400 - 2003 12734358
    also called MOR-1
    4 - 1576 - 418 - 2003 12734358
    also called MOR-10
    4 - 1652 - 446 - 2003 12734358
    also called MOR-1X
    4 - 1500 - 406 - 2003 12734358
    also called MOR-1B1
    4 - 2169 - 300 - 2003 12734358
    also called MOR-1G1
    4 - 2404 - 397 - 2003 12734358
    also called MOR-1B2
    4 - 2569 - 403 - 2003 12734358
    also called MOR-1B3
    4 - 1438 - 389 - 2003 12734358
    also called MOR-1B4
    4 - 1589 - - - 2003 12734358
    also called MOR-1B5
    - - 2738 - 493 - 2003 12734358
    also called MOR-1H
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbraindiencephalonhypothalamus  
     gangliasensory ganglia  highly Homo sapiens
    Visualeye    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervouspinealocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • seven transmembrane segments (7TM) receptor
  • HOMOLOGY
    interspecies homolog to murine Oprm
    Homologene
    FAMILY
  • G-protein coupled receptor 1 family
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    basic FUNCTION
  • principal sites of action of several endogenous opioid peptides, also major target for opioid analgesic agents and heroin
  • playing an important role in mediating the actions of morphine and morphine-like drugs
  • OPRM1 is more dependent on cholesterol for efficient signaling than OPRD1 which can be partly explained by localization of OPRM- but not OPRD receptors in cholesterol- and caveolin-enriched membrane domains
  • depressing cAMP levels, opening a G protein-modulated K+ channel and a third spliced variant acting as a morphine-6 beta-glucuronide receptor
  • both OPRD1 and OPRM1 agonists reduce depolarization-induced Ca(2+) currents in single small dorsal root ganglia neurons and inhibit afferent C-fiber synaptic transmission in the dorsal spinal cord
  • is the G-protein coupled receptor primarily responsible for mediating the analgesic and rewarding properties of opioid agonist drugs such as morphine, fentanyl, and heroin
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • form heteromers with OPRM1 and negatively regulate OPRM1-mediated spinal analgesia
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • REST (by NRSE element)
  • interacting with HINT1 and RGS20 for modulation of its signaling)
  • at the cellular level, PPP1R9B associates with OPRM1 in striatum and modulates OPRM1 signaling and endocytosis
  • interacting with RGS4 (acts as a GTPase accelerating protein to modulate OPRM1 and OPRD1 signaling)
  • PCBP1 is an expressional regulator of the mu-opioid receptor (OPRM1) gene
  • activation of OPRM1 leads to internalization of a cold-sensor TRPM8, which can be reversed by a follow-up treatment with the inverse OPRM1 agonist naloxone
  • cell & other
  • principle molecular target of opioid analgesics (
  • REGULATION
    activated by endomorphism 1 and 2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
  • heroin/cocaine dependence
  • to idiopathic generalized epilepsy or absence epilepsy
  • to drug and alcohol dependence
  • Variant & Polymorphism other
  • G118 allele increases the risk of idiopathic generalized epilepsy
  • SNP increasing the risk of drug and alcohol dependence
  • polymorphisms that may explain the variability seen in the clinical response to opiates, both from an analgesic and polymorphisms in OPRM1 that may explain the variability seen in the clinical response to opiates, both from an analgesic and alcohol and substance use disorders (ASUD) stand-point (Ravindranathana 2009)
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    dissociation of OPRM1 from OPRD1 in the cell membrane is a potential strategy to improve opioid analgesic therapies
    ANIMAL & CELL MODELS
  • Mor-1 KO mice with a disruption of exon 1 are unresponsive to morphine