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FLASH GENE

Symbol

OPRM1

contributors: mct/npt - updated : 12-10-2015

HGNC name	opioid receptor, mu 1
HGNC id	8156

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001008504 3 - 1867 NP_001008504 - 392 - 2003 12734358 also called MOR-1A NM_001145286 - - 2949 NP_001138759 - 300 - 2003 12734358 also called MOR-1K1 NM_001145281 4 - 1710 NP_001138753 - 319 - 2003 12734358 also called MOR-1G2 NM_000914 4 - 2178 NP_000905 - 400 - 2003 12734358 also called MOR-1 NM_001008503 4 - 1576 NP_001008503 - 418 - 2003 12734358 also called MOR-10 NM_001008505 4 - 1652 NP_001008505 - 446 - 2003 12734358 also called MOR-1X NM_001145282 4 - 1500 NP_001138754 - 406 - 2003 12734358 also called MOR-1B1 NM_001145280 4 - 2169 NP_001138752 - 300 - 2003 12734358 also called MOR-1G1 NM_001145283 4 - 2404 NP_001138755 - 397 - 2003 12734358 also called MOR-1B2 NM_001145284 4 - 2569 NP_001138756 - 403 - 2003 12734358 also called MOR-1B3 NM_001145285 4 - 1438 NP_001138757 - 389 - 2003 12734358 also called MOR-1B4 NM_001145286 4 - 1589 NP_001138758 - - - 2003 12734358 also called MOR-1B5 NM_001145279 - - 2738 NP_001138751 - 493 - 2003 12734358 also called MOR-1H

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain diencephalon hypothalamus       ganglia sensory ganglia     highly Homo sapiens Visual eye

cells

System Cell Pubmed Species Stage Rna symbol Nervous pinealocyte

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
	System Type Disorder Pubmed miscelleaneous pain   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