OPRM1

Summary

OPRM1 (opioid receptor mu 1, HGNC:8156) is a protein-coding gene on chromosome 6q25.2, encoding Mu-type opioid receptor (P35372). Receptor for endogenous opioids such as beta-endorphin and endomorphin.

This gene encodes one of at least three opioid receptors in humans; the mu opioid receptor (MOR). The MOR is the principal target of endogenous opioid peptides and opioid analgesic agents such as beta-endorphin and enkephalins. The MOR also has an important role in dependence to other drugs of abuse, such as nicotine, cocaine, and alcohol via its modulation of the dopamine system. The NM_001008503.2:c.118A>G allele has been associated with opioid and alcohol addiction and variations in pain sensitivity but evidence for it having a causal role is conflicting. Multiple transcript variants encoding different isoforms have been found for this gene. Though the canonical MOR belongs to the superfamily of 7-transmembrane-spanning G-protein-coupled receptors some isoforms of this gene have only 6 transmembrane domains.

Source: NCBI Gene 4988 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 522 total
• Druggable target: yes — 391 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000914

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8156
Approved symbol	OPRM1
Name	opioid receptor mu 1
Location	6q25.2
Locus type	gene with protein product
Status	Approved
Aliases	MOR1, MOP
Ensembl gene	ENSG00000112038
Ensembl biotype	protein_coding
OMIM	600018
Entrez	4988

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 16 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000229768, ENST00000330432, ENST00000337049, ENST00000360422, ENST00000414028, ENST00000419506, ENST00000428397, ENST00000434900, ENST00000435918, ENST00000452687, ENST00000518759, ENST00000519083, ENST00000519613, ENST00000520282, ENST00000520708, ENST00000521106, ENST00000522236, ENST00000522382, ENST00000522555, ENST00000522739, ENST00000523520, ENST00000524150, ENST00000524163

RefSeq mRNA: 19 — MANE Select: NM_000914 NM_000914, NM_001008503, NM_001008504, NM_001008505, NM_001145279, NM_001145280, NM_001145281, NM_001145282, NM_001145283, NM_001145284, NM_001145285, NM_001145286, NM_001145287, NM_001285522, NM_001285523, NM_001285524, NM_001285526, NM_001285527, NM_001285528

CCDS: CCDS43517, CCDS43518, CCDS47503, CCDS47504, CCDS47505, CCDS47506, CCDS47507, CCDS47508, CCDS55068, CCDS55069, CCDS55070, CCDS55071

Canonical transcript exons

ENST00000330432 — 4 exons

Exon	Start	End
ENSE00001239973	154118683	154132356
ENSE00001428473	154039240	154039834
ENSE00003508350	154089826	154090178
ENSE00003675593	154090952	154091472

Expression profiles

Bgee: expression breadth broad, 79 present calls, max score 75.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8656 / max 208.3405, expressed in 89 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70658	0.4104	73
70659	0.1694	51
70661	0.0909	41
70662	0.0656	29
70666	0.0368	17
70664	0.0353	7
70665	0.0352	9
70663	0.0165	3
70660	0.0054	1

Top tissues by expression

235 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.36	silver quality
right hemisphere of cerebellum	UBERON:0014890	73.22	gold quality
sperm	CL:0000019	72.65	silver quality
cerebellar hemisphere	UBERON:0002245	72.57	gold quality
cerebellar cortex	UBERON:0002129	72.53	gold quality
male germ cell	CL:0000015	70.85	silver quality
cerebellum	UBERON:0002037	69.66	gold quality
endometrium epithelium	UBERON:0004811	66.59	gold quality
left testis	UBERON:0004533	66.39	gold quality
right testis	UBERON:0004534	65.93	gold quality
testis	UBERON:0000473	64.97	gold quality
prefrontal cortex	UBERON:0000451	61.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	61.24	gold quality
nucleus accumbens	UBERON:0001882	61.10	gold quality
Brodmann (1909) area 10	UBERON:0013541	59.99	gold quality
mucosa of paranasal sinus	UBERON:0005030	59.73	gold quality
hypothalamus	UBERON:0001898	59.70	gold quality
superficial temporal artery	UBERON:0001614	57.84	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	57.04	gold quality
cingulate cortex	UBERON:0003027	56.48	gold quality
cerebellar vermis	UBERON:0004720	56.28	gold quality
anterior cingulate cortex	UBERON:0009835	56.24	gold quality
sural nerve	UBERON:0015488	56.18	gold quality
frontal cortex	UBERON:0001870	56.13	gold quality
right frontal lobe	UBERON:0002810	55.77	gold quality
ileal mucosa	UBERON:0000331	55.68	silver quality
neocortex	UBERON:0001950	55.52	gold quality
cranial nerve II	UBERON:0000941	54.82	gold quality
deltoid	UBERON:0001476	54.10	silver quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-83139	yes	126.38
E-ANND-3	yes	9.02
E-GEOD-124858	no	10.39
E-MTAB-5061	no	3.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CREB1, CXXC1, E2F1, FOXC1, GATA3, GLI3, HNRNPK, JUN, NFKB1, NFKB, PARP1, PAX3, POU2F1, REST, SMARCC1, SOX18, SOX21, SP1, SP3, SPI1, STAT1, STAT3, STAT6, TFAP2D, TFCP2, YY1

miRNA regulators (miRDB)

462 targeting OPRM1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5193	100.00	67.26	1744
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587

Literature-anchored findings (GeneRIF, showing 40)

• Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin: SNPs were detected, one in exon3, one in intron3 and one in the 3’ untranslated region (PMID:11933204)
• expression activates map kinases in cord blood hematopoietic stem cells (PMID:12031654)
• Two C-terminal amino acids, Ser(355) and Thr(357), required for short-term homologous desensitization of mu-opioid receptors. (PMID:12123746)
• dimerization of mu-opioid receptor expressed in insect cells (PMID:12141912)
• Lack of association of a single-nucleotide polymorphism of the mu-opioid receptor gene with anxiety-related traits (PMID:12210283)
• A118G single nucleotide polymorphism of the mu-opioid-receptor is among the protective factors against morphine-6-glucuronide-related opioid toxicity (PMID:12357145)
• These results suggest that oligomerization of chemokine receptor CCR5 and opioid receptors mu, delta and kappa on the cell membrane of human or monkey lymphocytes may modulate receptor functions. (PMID:12413885)
• two new human mu opioid receptors are the first human MOR-1 variants containing new exons and suggest that the complex splicing present in mice may extend to humans (PMID:12589820)
• This study suggested that there was significant population difference in the genotype distribution and allel frequency for the A118G and C17T polymorphisms in exon 1 of the OPM1 gene. (PMID:12657887)
• An alternatively spliced variant of the mu opiate receptor, mu3, is expressed on monocytes, granulocytes, and vascular endothelial cells that do not express the mu1 opiate receptor subtype. (PMID:12734358)
• interactions between helix VIII of the human mu-opioid receptors and the C terminus of periplakin disrupt G protein activation (PMID:12810704)
• OPRM1 may play a role in the pathophysiology of substance dependence and this role is population- and diagnostic-specific. (PMID:12815747)
• Genotyping of subjects with severe opioid dependence ( African-Americans amd European-Americans) and control subjects at SNPs in the OPRM1 gene. (PMID:12960749)
• substance P receptor dimerization with micro-opioid receptor, sequestering MOR-1 via an endocytotic pathway with delayed recycling and resensitization kinetics. (PMID:14532289)
• Mu opioid receptor gene polymorphism and neuroleptic-induced tardive dyskinesia in patients with schizophrenia. (PMID:14623376)
• Results show a strong functional relationship between alcohol craving, mood, and mu-OR binding in specific brain regions of recently abstinent, alcohol-dependent men. (PMID:14744466)
• amino acid substitution single-nucleotide polymorphism increrases risk of heroin asddiction in Swedish population. (PMID:15037869)
• FIndings fail to support the hypothesis that Asn40Asp alleles moderate the development of personality dimensions, as measured by the Five-Factor Model. (PMID:15167694)
• importance of STAT3 signaling in the regulation of neuronal growth and differentiation by the mu-opioid receptor. (PMID:15194868)
• NRSF can function as a repressor of MOR transcription in specific cells, via a mechanism dependent on the mu opioid receptor gene neuron-restrictive silencer element (PMID:15322094)
• Interleukin-6 strongly induces mu-opioid receptor mRNA in the human neuroblastoma cell line SH SY5Y. (PMID:15448191)
• The individual variations in mu receptor expression in these vascular tissues may explain the large variance in graft survival (PMID:15448587)
• alpha(2A)-AR and MOR hetero-oligomers, although they occur, do not have an obligatory functional influence on one another (PMID:15494033)
• OPRM1 may be a pain-relevant gene (PMID:15772909)
• No association has been revealed for the OPRM1 genotype and Korean patients with alcoholism compared to Korean control subjects without alcoholism. (PMID:15902904)
• 26-bp polypyrimidine stretch in MOR proximal promoter interacts with these PCBPs and activates MOR transcription (PMID:15933215)
• expression of the mu opioid receptor gene in lymphocytes is subject to the regulation of cis-elements upstream from the transcription initiation site (PMID:15988758)
• OPRM1-G118 is a functional variant with deleterious effects on both mRNA and protein yield (PMID:16046395)
• investigation of the ability of different opioid receptors to regulate the phosphorylation and degradation of tuberin (PMID:16053916)
• Nncoding region in the human OPRM1 gene should lead to a better understanding of the mechanisms underlying OPRM1 gene regulation and individual differences in sensitivity to opioids. (PMID:16122888)
• Polymorphisms in the mu-opioid receptor gene may potentially alter the clinical effects of opioid analgesics. (PMID:16133302)
• OPRM1 gene plays a role in T2DM susceptibility in African Americans. (PMID:16140553)
• OPRM1 intronic variants play a role in susceptibility to alcohol dependence and/or drug dependence in populations of European ancestry (PMID:16476706)
• SV1 and SV2 proteins are possible biological modulator of human mu-opioid receptor. (PMID:16580639)
• These results suggest that OPRM1 118G in addition to ALDH2 1510G might be one of the risk factors for alcohol dependence in Japanese people. (PMID:16679777)
• Results suggest that alterations in mu opioid receptors (OPRM1) and opioid neuropeptide systems might underlie enhanced opiate abuse vulnerability apparent in 118G polymorphic individuals. (PMID:16682632)
• Subjects with at least one copy of the 118G allele have increased basal levels of cortisol, which may influence the susceptibility to the stress responsive dyscrasia. (PMID:16794569)
• Changes in the inhibitory effects of opioid receptor agonists on intracellular cAMP were used as a marker of the function of mu opioid receptors. (PMID:16808998)
• Opioid receptor mu agonist morphine acts via inhibition of adenylate cyclase to inhibit protein kinase A-potentiated TRPV1 responses. (PMID:16842630)
• transcriptional regulation of MOR1 is modified by two genetic variations at positions of the mu-opioid receptor promoter (PMID:16843022)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	oprm1	ENSDARG00000039434
mus_musculus	Oprm1	ENSMUSG00000000766
rattus_norvegicus	Oprm1	ENSRNOG00000018191
drosophila_melanogaster	Rh7	FBGN0036260
caenorhabditis_elegans	trhr-1	WBGENE00016265

Paralogs (17): OPRK1 (ENSG00000082556), KISS1R (ENSG00000116014), OPRD1 (ENSG00000116329), OPRL1 (ENSG00000125510), NPBWR2 (ENSG00000125522), SSTR4 (ENSG00000132671), SSTR1 (ENSG00000139874), SSTR5 (ENSG00000162009), GPR149 (ENSG00000174948), SSTR2 (ENSG00000180616), UTS2R (ENSG00000181408), PTGDR2 (ENSG00000183134), CMKLR2 (ENSG00000183671), LTB4R (ENSG00000213903), LTB4R2 (ENSG00000213906), SSTR3 (ENSG00000278195), NPBWR1 (ENSG00000288611)

Protein

Protein identifiers

Mu-type opioid receptor — P35372 (reviewed: P35372)

Alternative names: Mu opiate receptor, Mu opioid receptor

All UniProt accessions (3): P35372, E7EW71, L0E130

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Couples to GNAS and is proposed to be involved in excitatory effects. Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity. Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.

Subunit / interactions. Forms homooligomers and heterooligomers with other GPCRs, such as OPRD1, OPRK1, OPRL1, NPFFR2, ADRA2A, SSTR2, CNR1 and CCR5 (probably in dimeric forms). Interacts with heterotrimeric G proteins; interaction with a heterotrimeric complex containing GNAI1, GNB1 and GNG2 stabilizes the active conformation of the receptor and increases its affinity for endomorphin-2, the synthetic opioid peptide DAMGO and for morphinan agonists. Interacts with PPL; the interaction disrupts agonist-mediated G-protein activation. Interacts (via C-terminus) with DNAJB4 (via C-terminus). Interacts with calmodulin; the interaction inhibits the constitutive activity of OPRM1; it abolishes basal and attenuates agonist-stimulated G-protein coupling. Interacts with FLNA, PLD2, RANBP9 and WLS and GPM6A. Interacts with RTP4. Interacts with SYP and GNAS. Interacts with RGS9, RGS17, RGS20, RGS4, PPP1R9B and HINT1. Interacts with SIGMAR1.

Subcellular location. Cell membrane. Cell projection. Axon. Perikaryon. Dendrite. Endosome Cytoplasm.

Tissue specificity. Expressed in brain. Isoform 16 and isoform 17 are detected in brain.

Post-translational modifications. Phosphorylated. Differentially phosphorylated in basal and agonist-induced conditions. Agonist-mediated phosphorylation modulates receptor internalization. Phosphorylated by GRK2 in a agonist-dependent manner. Phosphorylation at Tyr-168 requires receptor activation, is dependent on non-receptor protein tyrosine kinase Src and results in a decrease in agonist efficacy by reducing G-protein coupling efficiency. Phosphorylated on tyrosine residues; the phosphorylation is involved in agonist-induced G-protein-independent receptor down-regulation. Phosphorylation at Ser-377 is involved in G-protein-dependent but not beta-arrestin-dependent activation of the ERK pathway. Ubiquitinated. A basal ubiquitination does not seem to be related to degradation. Ubiquitination is increased upon formation of OPRM1:OPRD1 oligomers leading to proteasomal degradation; the ubiquitination is diminished by RTP4.

Polymorphism. Variant Asp-40 does not show altered binding affinities for most opioid peptides and alkaloids tested, but it binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately 3 times more tightly than the most common allelic form.

Miscellaneous. OPRM1 is the main physiological target for most clinically important opioid analgesics. OPRM1-mediated inhibition of voltage-gated calcium channels on central presynaptic terminals of primary afferent nociceptors is thought to be one of the primary mechanisms mediating analgesia at the spinal level. Opioid-induced hyperalgesic responses are observed following both acute and chronic dosing associated with cellular excitation. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the G-protein coupled receptor 1 family.

Isoforms (18)

UniProt ID	Names	Canonical?
P35372-1	1	yes
P35372-2	2, MOR1A, MOR-1A
P35372-3	3, MOR-1R, MOR-1X
P35372-4	4, MOR-1B3
P35372-5	5, MOR-1C, MOR-1O
P35372-6	6, MOR-1V, MOR-1Y, MOR-1Y2, MOR-1Y3
P35372-7	7, MOR-1B1
P35372-8	8, MOR-1B2
P35372-9	9, MOR-1B5
P35372-10	10, MOR-1i
P35372-11	11, MOR-1B4
P35372-12	12, MOR-1G1, MOR-1K
P35372-13	13, MOR-1G2
P35372-14	14, Mu3
P35372-15	15, MOR-1W
P35372-16	16, SV1
P35372-17	17, SV2
P35372-18	18, hMOR-1Z

RefSeq proteins (19): NP_000905, NP_001008503, NP_001008504, NP_001008505, NP_001138751, NP_001138752, NP_001138753, NP_001138754, NP_001138755, NP_001138756, NP_001138757, NP_001138758, NP_001138759, NP_001272451, NP_001272452, NP_001272453, NP_001272455, NP_001272456, NP_001272457 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000105	Mu_opioid_rcpt	Family
IPR000276	GPCR_Rhodpsn	Family
IPR001418	Opioid_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (83 total): splice variant 17, sequence variant 11, helix 10, topological domain 8, transmembrane region 7, sequence conflict 6, modified residue 5, glycosylation site 5, mutagenesis site 4, turn 3, strand 3, chain 1, short sequence motif 1, lipid moiety-binding region 1, disulfide bond 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
8Y72	ELECTRON MICROSCOPY	2.65
9PY4	ELECTRON MICROSCOPY	2.78
8EFO	ELECTRON MICROSCOPY	2.8
9WST	ELECTRON MICROSCOPY	2.8
8Y73	ELECTRON MICROSCOPY	2.84
8K9K	ELECTRON MICROSCOPY	2.98
10TM	ELECTRON MICROSCOPY	3
9PUD	ELECTRON MICROSCOPY	3
9PXY	ELECTRON MICROSCOPY	3
9PXV	ELECTRON MICROSCOPY	3.02
8K9L	ELECTRON MICROSCOPY	3.05
9PXX	ELECTRON MICROSCOPY	3.1
9PY2	ELECTRON MICROSCOPY	3.16
8EF6	ELECTRON MICROSCOPY	3.2
8EFB	ELECTRON MICROSCOPY	3.2
8EFL	ELECTRON MICROSCOPY	3.2
9PY3	ELECTRON MICROSCOPY	3.2
8F7Q	ELECTRON MICROSCOPY	3.22
9MQJ	ELECTRON MICROSCOPY	3.23
8F7R	ELECTRON MICROSCOPY	3.28
8EF5	ELECTRON MICROSCOPY	3.3
8EFQ	ELECTRON MICROSCOPY	3.3
9MQI	ELECTRON MICROSCOPY	3.3
9PPQ	ELECTRON MICROSCOPY	3.34
9PXU	ELECTRON MICROSCOPY	3.4
10TL	ELECTRON MICROSCOPY	3.5
9PU5	ELECTRON MICROSCOPY	3.5
9PXW	ELECTRON MICROSCOPY	3.8
9MQH	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35372-F1	77.40	0.48

Antibody-complex structures (SAbDab): 10 — 8EF5, 8EF6, 8EFB, 8EFL, 8EFO, 8F7Q, 8F7R, 8K9K, 8K9L, 8Y72

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 168, 365, 372, 377, 396, 353

Disulfide bonds (1): 142–219

Glycosylation sites (5): 9, 12, 33, 40, 48

Mutagenesis-validated functional residues (4):

Position	Phenotype
142	abolishes ligand binding; when associated with a-219 or s-219.
219	abolishes ligand binding; when associated with a-142 or s-142.
273	impairs interaction with calmodulin.
275	impairs interaction with calmodulin.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-111885	Opioid Signalling
R-HSA-202040	G-protein activation
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418594	G alpha (i) signalling events
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9022699	MECP2 regulates neuronal receptors and channels

MSigDB gene sets: 300 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_BEHAVIOR, YAGI_AML_WITH_INV_16_TRANSLOCATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_ADULT_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEUROGENESIS, HNF1_Q6, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, LHX3_01, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_MONOATOMIC_CATION_TRANSPORT

GO Biological Process (21): G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway (GO:0007197), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), neuropeptide signaling pathway (GO:0007218), sensory perception (GO:0007600), negative regulation of cell population proliferation (GO:0008285), sensory perception of pain (GO:0019233), G protein-coupled opioid receptor signaling pathway (GO:0038003), negative regulation of nitric oxide biosynthetic process (GO:0045019), behavioral response to ethanol (GO:0048149), positive regulation of neurogenesis (GO:0050769), negative regulation of cytosolic calcium ion concentration (GO:0051481), negative regulation of Wnt protein secretion (GO:0061358), positive regulation of ERK1 and ERK2 cascade (GO:0070374), regulation of cellular response to stress (GO:0080135), regulation of NMDA receptor activity (GO:2000310), signal transduction (GO:0007165), calcium ion transmembrane transport (GO:0070588), cellular response to morphine (GO:0071315)

GO Molecular Function (10): G-protein alpha-subunit binding (GO:0001965), G protein-coupled receptor activity (GO:0004930), beta-endorphin receptor activity (GO:0004979), voltage-gated calcium channel activity (GO:0005245), G-protein beta-subunit binding (GO:0031681), morphine receptor activity (GO:0038047), neuropeptide binding (GO:0042923), G protein-coupled opioid receptor activity (GO:0004985), protein binding (GO:0005515), G protein-coupled peptide receptor activity (GO:0008528)

GO Cellular Component (12): endosome (GO:0005768), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), axon (GO:0030424), dendrite (GO:0030425), neuron projection (GO:0043005), perikaryon (GO:0043204), synapse (GO:0045202), cytoplasm (GO:0005737), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
G alpha (i) signalling events	1
Opioid Signalling	1
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Signaling by Interleukins	1
Transcriptional Regulation by MECP2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	5
cellular anatomical structure	4
G protein-coupled receptor activity	3
endomembrane system	3
regulation of cellular process	2
protein binding	2
G protein-coupled opioid receptor activity	2
cytoplasm	2
intracellular membrane-bounded organelle	2
neuron projection	2
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
G protein-coupled acetylcholine receptor signaling pathway	1
phospholipase C activator activity	1
nervous system process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
sensory perception	1
nitric oxide biosynthetic process	1
negative regulation of biosynthetic process	1
regulation of nitric oxide biosynthetic process	1
adult behavior	1
response to ethanol	1
positive regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
positive regulation of nervous system development	1
regulation of biological quality	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of protein secretion	1
Wnt protein secretion	1
regulation of Wnt protein secretion	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
cellular response to stress	1

Protein interactions and networks

STRING

2234 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OPRM1	POMC	P01189	996
OPRM1	PENK	P01210	894
OPRM1	PDYN	P01213	875
OPRM1	COMT	P21964	871
OPRM1	ARRB2	P32121	861
OPRM1	ARRB1	P49407	828
OPRM1	PNOC	Q13519	820
OPRM1	SAG	P10523	742
OPRM1	SIGMAR1	Q99720	736
OPRM1	CRH	P06850	734
OPRM1	CRHR1	P34998	731
OPRM1	CCK	P06307	727
OPRM1	ANKK1	Q8NFD2	722
OPRM1	ADRB2	P07550	719
OPRM1	TRPV1	Q8NER1	712

IntAct

82 interactions, top by confidence:

A	B	Type	Score
WLS	OPRM1	psi-mi:“MI:0915”(physical association)	0.820
OPRM1	WLS	psi-mi:“MI:0915”(physical association)	0.820
OPRM1	WLS	psi-mi:“MI:0403”(colocalization)	0.820
RANBP9	OPRM1	psi-mi:“MI:0915”(physical association)	0.690
VAPA	OPRM1	psi-mi:“MI:0915”(physical association)	0.680
OPRM1	VAPA	psi-mi:“MI:0915”(physical association)	0.680
GJA4	OPRM1	psi-mi:“MI:0915”(physical association)	0.630
OPRM1	GJA4	psi-mi:“MI:0915”(physical association)	0.630
FLNA	OPRM1	psi-mi:“MI:0915”(physical association)	0.600
OPRM1	FLNA	psi-mi:“MI:0915”(physical association)	0.600
FLNA	OPRM1	psi-mi:“MI:0403”(colocalization)	0.600
COPS5	OPRM1	psi-mi:“MI:0915”(physical association)	0.580
OPRM1	AUP1	psi-mi:“MI:0915”(physical association)	0.580

BioGRID (217): AUP1 (Two-hybrid), COPS5 (Two-hybrid), GJA4 (Two-hybrid), DOK4 (Two-hybrid), DOK5 (Two-hybrid), KCNF1 (Two-hybrid), RANBP9 (Two-hybrid), SIAH1 (Two-hybrid), SIAH2 (Two-hybrid), VAPA (Two-hybrid), WLS (Two-hybrid), ZYX (Two-hybrid), OPRM1 (Reconstituted Complex), OPRM1 (Reconstituted Complex), RANBP9 (Reconstituted Complex)

ESM2 similar proteins: A5A4L1, B2ZI34, O08725, O54799, O62709, P14600, P21450, P21451, P21729, P24053, P24530, P25101, P25103, P26684, P28088, P28336, P30547, P30548, P30550, P32304, P32305, P33534, P33535, P34975, P35372, P35463, P41144, P41145, P42866, P47211, P48302, P52500, P56479, P56497, P79350, Q29010, Q2KIP6, Q5DUB3, Q5IS39, Q5IS84

Diamond homologs: A0T2N3, F1MV99, O00155, O00590, O08707, O08858, O09027, O35210, O77590, O88410, O89039, O97666, P0C5I1, P0C7U4, P11613, P21109, P25024, P25025, P25095, P25104, P25106, P29089, P29754, P29755, P30555, P30556, P30680, P30874, P30875, P30935, P30936, P30937, P30938, P31391, P32303, P32745, P33396, P33535, P34976, P34993

SIGNOR signaling

49 interactions.

A	Effect	B	Mechanism
RPN1	up-regulates	OPRM1	binding
GRK2	“down-regulates activity”	OPRM1	phosphorylation
OPRM1	“up-regulates activity”	GNAI1	binding
OPRM1	“up-regulates activity”	GNAI3	binding
OPRM1	“up-regulates activity”	GNAO1	binding
OPRM1	“up-regulates activity”	GNAZ	binding
MET-enkephalin	“up-regulates activity”	OPRM1	“chemical activation”
CAMK2A	down-regulates	OPRM1	phosphorylation
GRK3	“down-regulates activity”	OPRM1	phosphorylation
alvimopan	“down-regulates activity”	OPRM1	“chemical inhibition”
sufentanil	“up-regulates activity”	OPRM1	“chemical activation”
hydromorphone	“up-regulates activity”	OPRM1	“chemical activation”
nalbuphine	“up-regulates activity”	OPRM1	“chemical activation”
methylnaltrexone	“down-regulates activity”	OPRM1	“chemical inhibition”
2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol	“up-regulates activity”	OPRM1	“chemical activation”
PPBP	“down-regulates activity”	OPRM1	“chemical inhibition”
PDYN	“up-regulates activity”	OPRM1	“chemical activation”
3-N-Me-Phe-morphiceptin	“up-regulates activity”	OPRM1	“chemical activation”
Quadazocine	“down-regulates activity”	OPRM1	“chemical inhibition”
“Naloxone benzoylhydrazone”	“down-regulates activity”	OPRM1	“chemical inhibition”
Naltriben	“down-regulates activity”	OPRM1	“chemical inhibition”
morphine	“up-regulates activity”	OPRM1	“chemical activation”
beta-Funaltrexamine	“down-regulates activity”	OPRM1	“chemical inhibition”
(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-6-(phenylmethylene)-1,2,4,5,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one	“down-regulates activity”	OPRM1	“chemical inhibition”
bremazocine	“down-regulates activity”	OPRM1	“chemical inhibition”
Ethylketocyclazocine	“up-regulates activity”	OPRM1	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
protein localization to plasma membrane	5	18.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

522 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	9
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2010 predictions. Top by Δscore:

Variant	Effect	Δscore
6:154039833:AG:A	donor_loss	1.0000
6:154039834:GG:G	donor_loss	1.0000
6:154039835:G:A	donor_loss	1.0000
6:154039836:T:G	donor_loss	1.0000
6:154089817:A:AG	acceptor_gain	1.0000
6:154089818:T:G	acceptor_gain	1.0000
6:154089821:CCTA:C	acceptor_loss	1.0000
6:154089822:CTA:C	acceptor_loss	1.0000
6:154089823:TAGAT:T	acceptor_loss	1.0000
6:154089824:A:AG	acceptor_gain	1.0000
6:154089824:A:T	acceptor_loss	1.0000
6:154089825:G:A	acceptor_loss	1.0000
6:154089825:G:GG	acceptor_gain	1.0000
6:154089825:GA:G	acceptor_gain	1.0000
6:154089825:GAT:G	acceptor_gain	1.0000
6:154089825:GATA:G	acceptor_gain	1.0000
6:154089825:GATAC:G	acceptor_gain	1.0000
6:154090175:CAAGG:C	donor_loss	1.0000
6:154090178:GGTG:G	donor_loss	1.0000
6:154090179:G:GA	donor_loss	1.0000
6:154090950:A:AG	acceptor_gain	1.0000
6:154090951:G:A	acceptor_loss	1.0000
6:154090951:G:GA	acceptor_gain	1.0000
6:154090951:GGTT:G	acceptor_gain	1.0000
6:154160039:CACTG:C	acceptor_gain	1.0000
6:154160041:C:CC	acceptor_gain	1.0000
6:154160049:G:GC	acceptor_gain	1.0000
6:154168005:AACT:A	donor_gain	1.0000
6:154168109:CTCTT:C	acceptor_gain	1.0000
6:154168111:CTT:C	acceptor_gain	1.0000

AlphaMissense

2645 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:154039794:G:A	G84R	1.000
6:154039794:G:C	G84R	1.000
6:154039794:G:T	G84W	1.000
6:154039795:G:A	G84E	1.000
6:154039803:G:A	G87R	1.000
6:154039803:G:C	G87R	1.000
6:154039804:G:A	G87E	1.000
6:154039808:C:A	N88K	1.000
6:154039808:C:G	N88K	1.000
6:154089868:C:A	N111K	1.000
6:154089868:C:G	N111K	1.000
6:154089870:T:A	L112H	1.000
6:154089870:T:C	L112P	1.000
6:154089873:C:A	A113D	1.000
6:154089881:G:C	D116H	1.000
6:154089882:A:C	D116A	1.000
6:154089882:A:G	D116G	1.000
6:154089882:A:T	D116V	1.000
6:154089883:T:A	D116E	1.000
6:154089883:T:G	D116E	1.000
6:154089884:G:C	A117P	1.000
6:154089896:A:C	S121R	1.000
6:154089898:T:A	S121R	1.000
6:154089898:T:G	S121R	1.000
6:154089906:C:A	P124H	1.000
6:154089906:C:G	P124R	1.000
6:154089938:T:A	W135R	1.000
6:154089938:T:C	W135R	1.000
6:154089940:G:C	W135C	1.000
6:154089940:G:T	W135C	1.000

dbSNP variants (sampled 300 via entrez): RS1000000944 (6:154064551 G>T), RS1000019634 (6:154036666 TAAG>T), RS1000032055 (6:154064833 A>G), RS1000053465 (6:154211737 A>G), RS1000055462 (6:154106009 C>A), RS1000057954 (6:154174672 C>A), RS1000066930 (6:154195694 A>C,G), RS1000067835 (6:154042885 A>C), RS1000075416 (6:154218393 G>A), RS1000078855 (6:154028938 C>T), RS1000089436 (6:154084789 TA>T,TAA), RS1000090205 (6:154195540 G>C,T), RS1000094517 (6:154021604 CTATT>C), RS1000095572 (6:154111907 A>C), RS1000114813 (6:154171637 A>T)

Disease associations

OMIM: gene MIM:600018 | disease phenotypes: MIM:610064

GenCC curated gene-disease

Mondo (1): opioid dependence, susceptibility to, 1 (MONDO:0012402)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000973_6	Hypertension	5.000000e-06
GCST003127_8	Lipoprotein (a) levels	1.000000e-09
GCST004125_18	Type 2 diabetes (age of onset)	9.000000e-06
GCST004136_37	Methadone dose in opioid dependence	3.000000e-08
GCST006630_7	Diastolic blood pressure	3.000000e-11
GCST006638_2	Menstruation quality of life impact (fever)	2.000000e-08
GCST010242_100	HDL cholesterol levels	4.000000e-08
GCST010510_1	Opioid use disorder	8.000000e-10
GCST010988_380	Adult body size	4.000000e-10
GCST010989_113	Body size at age 10	2.000000e-17
GCST011155_14	Nontraumatic osteonecrosis of the femoral head	2.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0006925	lipoprotein A measurement
EFO:0007907	methadone dose measurement
EFO:0006336	diastolic blood pressure
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0010702	opioid use disorder
EFO:0009819	comparative body size at age 10, self-reported
EFO:1001930	idiopathic osteonecrosis of the femoral head

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL2095149 (SELECTIVITY GROUP), CHEMBL2095156 (SELECTIVITY GROUP), CHEMBL2095181 (PROTEIN FAMILY), CHEMBL233 (SINGLE PROTEIN), CHEMBL3301384 (PROTEIN COMPLEX), CHEMBL3883321 (PROTEIN COMPLEX), CHEMBL3885538 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

391 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 676,491 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1200531	ALFENTANIL HYDROCHLORIDE	4	1,169
CHEMBL19019	NALTREXONE	4	34,647
CHEMBL70	MORPHINE	4	128,573
CHEMBL1254682	LEVALLORPHAN	4	7,151
CHEMBL80	NALOXONE	4	38,742
CHEMBL1201149	NALTREXONE HYDROCHLORIDE	4	3,278
CHEMBL1718	NALOXONE HYDROCHLORIDE	4	4,865
CHEMBL607	MEPERIDINE	4	43,837
CHEMBL963	OXYMORPHONE	4	25,955
CHEMBL100116	PENTAZOCINE	4	33,194
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1017	TELMISARTAN	4	27,457
CHEMBL1023	BEXAROTENE	4	40,951
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1078261	PROPIVERINE	4	4,890
CHEMBL1088	MESORIDAZINE	4	12,814
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1104	EDROPHONIUM	4	17,617
CHEMBL1106	EPINASTINE	4
CHEMBL111	RIMONABANT	4
CHEMBL1112	ARIPIPRAZOLE	4
CHEMBL1113	AMOXAPINE	4
CHEMBL1118	DESVENLAFAXINE	4
CHEMBL1138	EZETIMIBE	4
CHEMBL114	SAQUINAVIR	4
CHEMBL1171837	PONATINIB	4
CHEMBL1175	DULOXETINE	4
CHEMBL1186579	METHYLNALTREXONE	4

PharmGKB: 1 entry (VIP=true, CPIC=true)

PharmGKB clinical annotations

133 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10457090	Metabolism/PK	3	cotinine;nicotine
rs10457090	Toxicity	3	opioids	Opioid-Related Disorders
rs10485057	Toxicity	3	nicotine	Tobacco Use Disorder
rs10485057	Dosage	3	ethanol
rs10485057	Dosage	3	nicotine
rs10485057	Toxicity	3	ethanol	Alcohol abuse
rs10485058	Efficacy	3	methadone	Opioid-Related Disorders
rs1074287	Metabolism/PK	3	cotinine;nicotine
rs12209447	Metabolism/PK	3	cotinine;nicotine
rs1323040	Dosage	3	sufentanil
rs1381376	Toxicity	3	ethanol	Alcohol abuse
rs1461773	Efficacy	3	ethanol
rs1799971	Metabolism/PK	3	cotinine;nicotine
rs1799971	Toxicity	3	tianeptine	Major Depressive Disorder;suicidal ideation
rs1799971	Toxicity	3	ethanol	Alcohol abuse
rs1799971	Efficacy	3	naloxone
rs1799971	Efficacy	3	alfentanil	Pain
rs1799971	Toxicity	3	alfentanil
rs1799971	Metabolism/PK	3	alfentanil	Pain
rs1799971	Dosage	3	alfentanil	Pain
rs1799971	Toxicity	3	buprenorphine;fentanyl;tramadol	adverse events;Opioid-Related Disorders
rs1799971	Toxicity	3	fentanyl	Somnolence
rs1799971	Efficacy	3	fentanyl	Pain
rs1799971	Other	3	Analgesics;Antiinflammatory agents;non-steroids;Ergot alkaloids;opioids;sumatriptan	Substance Withdrawal Syndrome
rs1799971	Dosage	3	fentanyl	Pain;Pain;Postoperative
rs1799971	Toxicity	3	hydrocodone	Constipation;Dry mouth;Respiratory Insufficiency
rs1799971	Toxicity	3	morphine	Neonatal Abstinence Syndrome
rs1799971	Dosage	3	codeine
rs1799971	Efficacy	3	acetaminophen;tramadol	Neuropathic pain
rs1799971	Toxicity	3	opioids	adverse events;Nausea;Vomiting
rs1799971	Efficacy	3	opioids	Pain;Postoperative
rs1799971	Efficacy	3	oxycodone
rs1799971	Toxicity	3	methadone	Opioid-Related Disorders;Sleep Disorders
rs1799971	Toxicity	3	methadone	Neonatal Abstinence Syndrome
rs1799971	Efficacy	3	Opioid anesthetics;Other general anesthetics;volatile anesthetics
rs1799971	Dosage	3	opioids	Pain;Pain;Postoperative
rs1799971	Toxicity	3	morphine	Sleep Apnea Syndromes
rs1799971	Toxicity	3	opioids	Sleep Disorders
rs1799971	Dosage	3	sufentanil	Pain;Pain;Postoperative
rs1799971	Toxicity	3	ethanol

PharmGKB variants

112 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs510769	OPRM1	3	3.50	4	opioids;amphetamine;cotinine;nicotine;heroin
rs544093	OPRM1	3	2.50	1	carboplatin;docetaxel;paclitaxel
rs558025	OPRM1	3	0.00	1	methadone
rs1799971	OPRM1	3	8.00	54	Drugs used in nicotine dependence;nicotine;ethanol;morphine;opioids;sufentanil;heroin;tramadol;buprenorphine;fentanyl;tramadol;alfentanil;fentanyl
rs2075572	OPRM1	3	3.25	5	methadone;cotinine;nicotine;ethanol;heroin;methamphetamine
rs2281617	IPCEF1, OPRM1	3	1.00	1	amphetamine
rs3778151	OPRM1	3	1.50	1	heroin
rs9384179	OPRM1		0.00	0
rs9479757	OPRM1	3	2.75	3	heroin;opioids
rs10485058	OPRM1	3	1.50	1	methadone
rs648893	OPRM1	3	0.00	1	opioids
rs17174629	OPRM1		0.00	0
rs1799972	OPRM1	3	3.00	2	cocaine;ethanol;nicotine;opioids
rs1074287	OPRM1	3	2.25	1	cotinine;nicotine
rs6912029	OPRM1	3	1.75	1	cotinine;nicotine
rs12209447	OPRM1	3	2.25	1	cotinine;nicotine
rs3798676	OPRM1	3	2.25	1	cotinine;nicotine
rs553202	OPRM1	3	3.25	2	cotinine;nicotine;ethanol
rs499796	OPRM1		0.00	0
rs7748401	OPRM1	3	2.25	1	cotinine;nicotine
rs495491	OPRM1	3	6.00	5	cotinine;nicotine;heroin;cocaine;ethanol;opioids
rs10457090	OPRM1	3	3.25	2	cotinine;nicotine;opioids
rs589046	OPRM1	3	3.25	2	cotinine;nicotine;opioids
rs3778152	OPRM1	3	2.25	1	cotinine;nicotine
rs563649	OPRM1	3	2.25	1	cotinine;nicotine
rs62638690	OPRM1	3	3.00	1	cocaine;heroin
rs17174794	OPRM1		0.00	0
rs17174801	OPRM1		0.00	0
rs17180982	OPRM1		0.00	0
rs1319339	OPRM1		0.00	0
rs7776341	OPRM1		0.00	0
rs540825	OPRM1	3	2.00	1	fentanyl
rs677830	OPRM1		0.00	0
rs562859	OPRM1	3	3.50	1	heroin
rs548646	OPRM1	3	3.25	2	opioids;ethanol
rs1323042	OPRM1		0.00	0
rs618207	OPRM1		0.00	0
rs639855	OPRM1		0.00	0
rs497976	OPRM1		0.00	0
rs12210856	OPRM1		0.00	0

PharmGKB dosing guidelines

2 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	alfentanil;buprenorphine;codeine;fentanyl;hydrocodone;hydromorphone;levomethadone;morphine;naltrexone;remifentanil;sufentanil;tramadol	Annotation of CPIC Guideline for alfentanil, buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, levomethadone, morphine, naltrexone, remifentanil, sufentanil, tramadol and COMT, OPRM1
CPIC	methadone;oxycodone	Annotation of CPIC Guideline for methadone, oxycodone and COMT, CYP2D6, OPRM1

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Opioid receptors

Most potent curated ligand interactions (113 total), top 25:

Ligand	Action	Affinity	Parameter
carfentanil	Agonist	10.62	pKi
etonitazene	Full agonist	10.52	pEC50
isotonitazene	Full agonist	10.3	pEC50
naloxonazine	Antagonist	10.3	pKi
samidorphan	Antagonist	10.28	pKi
[3H]diprenorphine	Antagonist	10.1	pKd
(-)-cyclazocine	Partial agonist	10.0	pKi
quadazocine	Antagonist	10.0	pKi
butorphanol	Partial agonist	9.92	pKi
sufentanil	Full agonist	9.9	pKi
levorphanol	Agonist	9.89	pIC50
lofentanil	Agonist	9.86	pEC50
BU72	Agonist	9.82	pIC50
(-)-bremazocine	Antagonist	9.7	pKi
naltrexone	Antagonist	9.7	pKi
CTOP	Antagonist	9.7	pKi
hydromorphone	Agonist	9.55	pKi
ethylketocyclazocine	Full agonist	9.5	pKi
etorphine	Full agonist	9.5	pKi
nalmefene	Antagonist	9.5	pKi
β-FNA	Antagonist	9.5	pKi
NFP	Antagonist	9.44	pKi
atoxifent	Agonist	9.41	pEC50
GSK1521498	Antagonist	9.38	pKi
alvimopan	Antagonist	9.33	pKi

Binding affinities (BindingDB)

1273 measured of 1674 human assays (1742 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
BW373U86	KI	0.01 nM
CAS_111555-58-9	KI	0.01 nM
CHEMBL4798954	EC50	0.017 nM
(1R,9R,10S)-N-benzyl-17-(cyclopropylmethyl)-4-methoxy-11-oxa-17-azapentacyclo[7.5.3.210,13.01,10.02,7]nonadeca-2(7),3,5-trien-13-amine	KI	0.026 nM	US-9862726: Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans
(1S,9R,10S,12S)-16-(cyclopropylmethyl)-N-[(3,4-dichlorophenyl)methyl]-4,10-dihydroxy-16-azatetracyclo[7.4.3.01,10.02,7]hexadeca-2(7),3,5-triene-12-carboxamide	EC50	0.03 nM	US-9656962: Ring-contracted morphinans and the use thereof
N-[(1R,9R,10S)-17-(cyclopropylmethyl)-4-methoxy-11-oxa-17-azapentacyclo[7.5.3.210,13.01,10.02,7]nonadeca-2(7),3,5-trien-13-yl]benzamide	KI	0.032 nM	US-9862726: Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans
(1S,2S,6R,14R,16R)-5-(cyclopropylmethyl)-16-(furan-3-ylmethoxymethyl)-15-methoxy-16-methyl-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol	EC50	0.037 nM	US-9988392: 7-beta-alkyl analogs of orvinols
(1S,2S,6R,14R,16R)-5-(cyclopropylmethyl)-15-methoxy-16-methyl-16-(phenylmethoxymethyl)-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol	EC50	0.047 nM	US-9988392: 7-beta-alkyl analogs of orvinols
(1R,9R,10S)-N-(cyclohexylmethyl)-17-(cyclopropylmethyl)-4-methoxy-11-oxa-17-azapentacyclo[7.5.3.210,13.01,10.02,7]nonadeca-2(7),3,5-trien-13-amine	KI	0.052 nM	US-9862726: Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans
4-chloro-N-[(1R,9R,10S)-17-(cyclopropylmethyl)-4-methoxy-11-oxa-17-azapentacyclo[7.5.3.210,13.01,10.02,7]nonadeca-2(7),3,5-trien-13-yl]benzenesulfonamide	KI	0.057 nM	US-9862726: Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans
N-[(1R,9R,10S)-17-(cyclopropylmethyl)-4-hydroxy-11-oxa-17-azapentacyclo[7.5.3.210,13.01,10.02,7]nonadeca-2(7),3,5-trien-13-yl]-2,2-dimethylpropanamide	KI	0.059 nM	US-9862726: Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans
N-[(1R,9R,10S)-17-(cyclopropylmethyl)-4-hydroxy-11-oxa-17-azapentacyclo[7.5.3.210,13.01,10.02,7]nonadeca-2(7),3,5-trien-13-yl]benzamide	KI	0.062 nM	US-9862726: Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans
(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-11,15-dimethoxy-16-[(2-methylphenyl)methoxymethyl]-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene	KI	0.07 nM	US-8530494: Buprenophine analogs
14-O-phenylpropylnaltrexone	EC50	0.075 nM	US-10231963: Methods for treating depressive symptoms
(4R,4aS,12bS)-3-(cyclopropylmethyl)-9-hydroxy-4a-(3-phenylpropoxy)-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one	IC50	0.079 nM	US-10736890: Methods for treating depressive symptoms
(1S,2S,6R,14R,15R,16R)-11,15-dimethoxy-5-methyl-16-(naphthalen-1-ylmethoxymethyl)-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene	KI	0.08 nM	US-8530494: Buprenophine analogs
(1S,2S,6R,14R,16R)-5-(cyclopropylmethyl)-11,15-dimethoxy-16-methyl-16-(phenylmethoxymethyl)-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene	EC50	0.085 nM	US-9988392: 7-beta-alkyl analogs of orvinols
(1S,9R,10S,12S)-N-benzyl-16-(cyclopropylmethyl)-4,10-dihydroxy-16-azatetracyclo[7.4.3.01,10.02,7]hexadeca-2(7),3,5-triene-12-carboxamide	EC50	0.094 nM	US-9656962: Ring-contracted morphinans and the use thereof
(1R,9R,10S)-13-amino-17-(cyclopropylmethyl)-11-oxa-17-azapentacyclo[7.5.3.210,13.01,10.02,7]nonadeca-2(7),3,5-trien-4-ol	KI	0.096 nM	US-9862726: Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans
(1S,2S,6R,14R,15R,16R)-11,15-dimethoxy-5-methyl-16-[(2-methylphenyl)methoxymethyl]-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene	KI	0.1 nM	US-8530494: Buprenophine analogs
NSC_104911	KI	0.1 nM
CHEMBL3309518	KI	0.11 nM
(1S,9R,10R)-5-amino-20-(cyclopropylmethyl)-6-thia-4,20-diazapentacyclo[8.7.3.0^{1,9}.0^{3,7}.0^{12,17}]icosa-3(7),4,12(17),13,15-pentaen-15-ol	KI	0.12 nM
(2S)-2-amino-N-[[(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-11-hydroxy-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-16-yl]methyl]-3-(4-hydroxyphenyl)propanamide	KI	0.13 nM	US-8969358: Buprenorphine analogs
d-Phe-d-Phe-d-Nle-d-Arg-NH2	KI	0.146 nM
(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-11,15-dimethoxy-16-[(3-methylphenyl)methoxymethyl]-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene	KI	0.15 nM	US-8530494: Buprenophine analogs
(1S,2S,6R,14R,15R,16R)-16-(cyclobutylmethoxymethyl)-11,15-dimethoxy-5-methyl-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene	KI	0.15 nM	US-8530494: Buprenophine analogs
(2S)-2-acetamido-N-[[(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-11-hydroxy-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-16-yl]methyl]-3-phenylpropanamide	KI	0.16 nM	US-8969358: Buprenorphine analogs
(6R,6aS,7aS,10aS,11aR)-14- (cyclopropylmethyl)-2,6a-dihydroxy- 5,6,6a,7,7a,8,10a,11-octahydro-6,11a- (epiminoethano)naphtho[2,1-f]indol- 9(10H)-one	KI	0.16 nM	US-10435406: 6,7-cyclicmorphinan derivatives and use thereof
17-Methyl-17’-cyclopropylmethyl-3’-hydroxy-6,6’,7,7’-tetradehydro-4,5 alpha : 4’,5’ alpha-diepoxy-6,6’-(imino)[7,7’-bimorphinan]-3,14’-diol	KI	0.16 nM
(2S,6R)-11,15-dimethoxy-5-methyl-16-(phenylmethoxymethyl)-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene	KI	0.17 nM	US-8530494: Buprenophine analogs
[D-Ala2-D-Leu5]enkephalin	KI	0.18 nM
(4R,4aS,12bS)-9-hydroxy-4a-(3-phenylpropoxy)-3-prop-2-enyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one	IC50	0.18 nM	US-10736890: Methods for treating depressive symptoms
CHEMBL3309515	KI	0.18 nM
NSC_61677	KI	0.18 nM
(1S,10R,11R)-21-(cyclopropylmethyl)-16-hydroxy-5-oxo-4,21-diazapentacyclo[9.7.3.01,10.03,8.013,18]henicosa-3,6,13(18),14,16-pentaene-6-carboxamide	KI	0.19 nM	US-8980906: Pyridonemorphinan analogs and biological activity on opioid receptors
(4R,4aS,7aR,12bS)-9-hydroxy-4a-(3-phenylpropoxy)-3-prop-2-enyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one	EC50	0.19 nM	US-10231963: Methods for treating depressive symptoms
(1S,9R,10R,13S)-17-(cyclopropylmethyl)-4-hydroxyspiro[17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene-13,5’-imidazolidine]-2’,4’-dione	KI	0.2 nM	US-8987287: Spirocyclic morphinans and their use
(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2-fluorophenyl)methoxymethyl]-15-methoxy-5-methyl-13-oxa-5-azoniahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol	KI	0.2 nM	US-9096606: Quarternized buprenorphine analogs
(1S,9R,10S,12R)-16-(cyclopropylmethyl)-N-[(3,4-dichlorophenyl)methyl]-4,10-dihydroxy-16-azatetracyclo[7.4.3.01,10.02,7]hexadeca-2(7),3,5-triene-12-carboxamide	EC50	0.2 nM	US-9656962: Ring-contracted morphinans and the use thereof
(1S,2S,6R,14R,16R)-16-(1-benzothiophen-2-ylmethoxymethyl)-15-methoxy-5,16-dimethyl-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol	EC50	0.24 nM	US-9988392: 7-beta-alkyl analogs of orvinols
CHEMBL3291214	KI	0.24 nM
CHEMBL4747769	EC50	0.24 nM
(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(3-fluorophenyl)methoxymethyl]-15-methoxy-5-methyl-13-oxa-5-azoniahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol	KI	0.25 nM	US-9096606: Quarternized buprenorphine analogs
CHEMBL2113304	EC50	0.25 nM
CAS_156889	KI	0.25 nM
(1S,2S,6R,14R,15R,16R)-16-[(3-chlorophenyl)methoxymethyl]-5-(cyclopropylmethyl)-15-methoxy-5-methyl-13-oxa-5-azoniahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol	KI	0.27 nM	US-9096606: Quarternized buprenorphine analogs
(1S,2S,6R,14R,16R)-16-(1-benzothiophen-2-ylmethoxymethyl)-5-(cyclopropylmethyl)-15-methoxy-16-methyl-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol	EC50	0.27 nM	US-9988392: 7-beta-alkyl analogs of orvinols
(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-11,15-dimethoxy-16-(2-phenylmethoxypropan-2-yl)-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene	EC50	0.28 nM	US-9221831: Buprenorphine analogs
(1S,2S,6R,15R)-5-(cyclopropylmethyl)-16-[(2R)-2-hydroxy-4-thiophen-2-ylbutan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol	IC50	0.28 nM	US-10736890: Methods for treating depressive symptoms

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL58362
11.00	Ki	0.01	nM	CHEMBL326684
11.00	Ki	0.01	nM	CHEMBL199832
10.96	Ki	0.0109	nM	CHEMBL4550234
10.96	Ki	0.0109	nM	CHEMBL4521879
10.96	Ki	0.0109	nM	CHEMBL4439415
10.96	Ki	0.0109	nM	CHEMBL4450250
10.96	Ki	0.011	nM	CHEMBL5175179
10.90	IC50	0.0125	nM	CHEMBL443311
10.89	Ki	0.0128	nM	CHEMBL2334775
10.89	Ki	0.013	nM	CHEMBL331883
10.86	Ki	0.0137	nM	CHEMBL2334774
10.85	EC50	0.014	nM	CHEMBL4588535
10.85	Ki	0.014	nM	CHEMBL5182849
10.82	Ki	0.015	nM	CHEMBL464230
10.80	Ki	0.016	nM	CHEMBL583066
10.80	IC50	0.016	nM	CHEMBL4169199
10.77	EC50	0.017	nM	CHEMBL4798954
10.74	Ki	0.018	nM	CHEMBL2208358
10.72	Ki	0.019	nM	CHEMBL6067846
10.70	Ki	0.02	nM	NALTREXONE
10.70	Ki	0.02	nM	CHEMBL12391
10.68	Ki	0.021	nM	CHEMBL2208348
10.68	Ki	0.021	nM	CHEMBL5431513
10.62	Ki	0.024	nM	CARFENTANIL
10.59	Ki	0.026	nM	CHEMBL571767
10.55	IC50	0.028	nM	CHEMBL267027
10.55	EC50	0.028	nM	CHEMBL4578287
10.53	Ki	0.0298	nM	CHEMBL452991
10.52	IC50	0.03	nM	CHEMBL217395
10.52	EC50	0.03	nM	CHEMBL5186887
10.51	Ki	0.031	nM	CHEMBL3759292
10.49	Ki	0.0322	nM	CHEMBL2334772
10.49	Ki	0.032	nM	CHEMBL5176887
10.48	EC50	0.0334	nM	CHEMBL2163916
10.47	EC50	0.0342	nM	CHEMBL2163917
10.43	Ki	0.037	nM	CHEMBL4276875
10.40	EC50	0.0397	nM	CHEMBL2334770
10.40	Ki	0.04	nM	CHEMBL3919397
10.40	EC50	0.04	nM	CHEMBL2113666
10.40	EC50	0.04	nM	CHEMBL607125
10.40	EC50	0.04	nM	ENDOMORPHIN 2
10.40	EC50	0.04	nM	CHEMBL5757634
10.39	Ki	0.0405	nM	CHEMBL2334773
10.38	Ki	0.042	nM	CHEMBL3758712
10.37	Ki	0.043	nM	CHEMBL300662
10.32	Ki	0.048	nM	CHEMBL4103328
10.30	Ki	0.05	nM	CHEMBL3893577
10.30	Ki	0.05	nM	CHEMBL3908275
10.30	Ki	0.05	nM	CHEMBL3939227

PubChem BioAssay actives

2764 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[(3R,4S)-1-[(2R)-2-hydroxy-2-phenylethyl]-3-methylpiperidin-4-yl]-N-phenylpropanamide	150845: Binding affinity against Opioid receptor mu 1	ki	<0.0001	uM
(5R,8S,11S,14S)-14-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-8,11-dibenzyl-7,10,13-trioxo-1,3-dithia-6,9,12-triazacyclopentadecane-5-carboxamide	1274735: Binding affinity at mu opioid receptor (unknown origin)	ki	<0.0001	uM
(E)-N-[(4R,4aS,7aR,12bR)-9-hydroxy-3-methyl-7-oxo-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-yl]-3-(2-methylphenyl)prop-2-enamide	269575: Stimulation of [35S]GTPgammaS binding to human recombinant MOR	ec50	<0.0001	uM
methyl 1-(2-hydroxy-2-phenylethyl)-4-(N-propanoylanilino)piperidine-4-carboxylate	1611652: Agonist activity at human MOR expressed in CHO-K1 cells assessed as cAMP accumulation incubated for 30 mins and measured after 1 hr by Eu-cAMP tracer based TR-FRET assay	ec50	<0.0001	uM
(3R)-2-[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-N-(2-anilino-2-oxoethyl)-3,4-dihydro-1H-isoquinoline-3-carboxamide	1274735: Binding affinity at mu opioid receptor (unknown origin)	ki	<0.0001	uM
N-[(4R,4aR,7R,7aR,12bS)-3-(cyclopropylmethyl)-9-hydroxy-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-3-iodobenzamide	2007399: Binding affinity to MOR (unknown origin) assessed as inhibition constant by radioligand binding assay	ki	<0.0001	uM
1-[2-(3-chlorophenyl)ethyl]-3-[2-(dimethylamino)-2-(3-fluorophenyl)ethyl]urea	2135041: Agonist activity at human MOR expressed in CHO-K1 cells co-expressed with Galphai by cAMP assay	ec50	<0.0001	uM
1-[2-(dimethylamino)-2-(3-fluorophenyl)ethyl]-3-[2-(4-fluorophenyl)ethyl]urea	2135041: Agonist activity at human MOR expressed in CHO-K1 cells co-expressed with Galphai by cAMP assay	ec50	<0.0001	uM
1-[2-(dimethylamino)-2-(3-fluorophenyl)ethyl]-3-[(4-fluorophenyl)methyl]urea	2135041: Agonist activity at human MOR expressed in CHO-K1 cells co-expressed with Galphai by cAMP assay	ec50	<0.0001	uM
(4R,4aS,7aS,12bS)-3-methyl-4a-phenylmethoxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-9-ol	1476816: Displacement of [3H]-DAMGO from recombinant human MOR expressed in CHO cell membranes after 60 mins by liquid scintillation counting	ki	<0.0001	uM
(2S)-2-amino-N-[[(5R)-3-[(2R)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2,4-dioxo-1,3-oxazolidin-5-yl]methyl]-3-(4-hydroxyphenyl)propanamide	1355425: Agonist activity at human mu opioid receptor expressed in HEK293 assessed as inhibition forskolin-induced cAMP accumulation after 15 mins by EIA	ic50	<0.0001	uM
(2R)-2-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-5-(diaminomethylideneamino)pentanamide	1409275: Displacement of [3H]DAMGO from human MOR expressed in CHO cell membranes after 60 mins by liquid scintillation counting	ki	<0.0001	uM
2-[[[(2S)-2-[[(2R)-2-[[2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-methylamino]propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-(furan-2-yl)methyl]prop-2-enamide	1609950: Displacement of [3H]DAMGO from mu opioid receptor (unknown origin) expressed in HEK293 cells after 1 hr by liquid scintillation counting	ki	<0.0001	uM
2-[[[(2S)-2-[[(2R)-2-[[2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-methylamino]propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-phenylmethyl]prop-2-enamide	1609950: Displacement of [3H]DAMGO from mu opioid receptor (unknown origin) expressed in HEK293 cells after 1 hr by liquid scintillation counting	ki	<0.0001	uM
2-[[[(2S)-2-[[(2R)-2-[[2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-methylamino]propanoyl]amino]-3-phenylpropanoyl]amino]-phenylmethyl]prop-2-enamide	1609950: Displacement of [3H]DAMGO from mu opioid receptor (unknown origin) expressed in HEK293 cells after 1 hr by liquid scintillation counting	ki	<0.0001	uM
2-[[[(2S)-2-[[(2R)-2-[[2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-methylamino]propanoyl]amino]-3-phenylpropanoyl]amino]-(furan-2-yl)methyl]prop-2-enamide	1609950: Displacement of [3H]DAMGO from mu opioid receptor (unknown origin) expressed in HEK293 cells after 1 hr by liquid scintillation counting	ki	<0.0001	uM
methyl 1-[2-(2-hydroxyphenyl)ethyl]-4-(N-propanoylanilino)piperidine-4-carboxylate	1611652: Agonist activity at human MOR expressed in CHO-K1 cells assessed as cAMP accumulation incubated for 30 mins and measured after 1 hr by Eu-cAMP tracer based TR-FRET assay	ec50	<0.0001	uM
methyl 1-[2-(4-hydroxyphenyl)ethyl]-4-(N-propanoylanilino)piperidine-4-carboxylate	1611652: Agonist activity at human MOR expressed in CHO-K1 cells assessed as cAMP accumulation incubated for 30 mins and measured after 1 hr by Eu-cAMP tracer based TR-FRET assay	ec50	<0.0001	uM
methyl 1-[2-(3-hydroxyphenyl)ethyl]-4-(N-propanoylanilino)piperidine-4-carboxylate	1611652: Agonist activity at human MOR expressed in CHO-K1 cells assessed as cAMP accumulation incubated for 30 mins and measured after 1 hr by Eu-cAMP tracer based TR-FRET assay	ec50	<0.0001	uM
N-[(4R,4aS,7aR,12bR)-3-(cyclopropylmethyl)-9-hydroxy-7-oxo-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-yl]-3-(4-chlorophenyl)propanamide	273141: Activity at human recombinant mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTP-gamma-S binding	ic50	<0.0001	uM
N-[(4R,4aS,7aR,12bR)-3-(cyclopropylmethyl)-9-methoxy-7-oxo-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-yl]-3-(4-chlorophenyl)propanamide	273141: Activity at human recombinant mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTP-gamma-S binding	ic50	<0.0001	uM
(4R,4aS,7aR,12bR)-4a-[3-(4-chlorophenyl)propylamino]-3-(cyclopropylmethyl)-9-hydroxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one	273141: Activity at human recombinant mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTP-gamma-S binding	ic50	<0.0001	uM
(1R,5S,9S)-5-(3-hydroxyphenyl)-2-(2-phenylethyl)-2-azabicyclo[3.3.1]nonan-9-ol	1685500: Agonist activity at human MOR expressed in CHOK1 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by luminescence assay	ec50	<0.0001	uM
methyl (3R,4S)-3-methyl-1-(2-phenylethyl)-4-(N-propanoylanilino)piperidine-4-carboxylate	150985: Competitive binding displacement analyses was performed from permanently transfected HEK293 cells expressing Opioid receptor mu 1	ki	0.0001	uM
(2S)-1-[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]pyrrolidine-2-carboxamide	1409273: Agonist activity at human MOR expressed in CHO cell membranes after 60 mins by [35S]GTPgammaS binding assay	ec50	0.0001	uM
methyl 4-[4-hydroxy-4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]-2,2-diphenylbutanoate	239449: Binding affinity for recombinant human mu-opioid receptor was determined by using [3H]- diprenophine radioligand	ki	0.0001	uM
N-[(3R,4R)-1-[(2S)-2-hydroxy-2-phenylethyl]-3-methylpiperidin-4-yl]-N-phenylpropanamide	150845: Binding affinity against Opioid receptor mu 1	ki	0.0001	uM
bis[(1R,9R,10R)-17-(cyclopropylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-yl] butanedioate	151001: Inhibitory activity against Opioid receptor mu 1 in chinese Hamster Ovary (CHO) cells membranes was determined using [3H]-DAMGO radioligand	ki	0.0001	uM
2-(18F)fluoro-N-[4-(methoxymethyl)-1-(2-thiophen-2-ylethyl)piperidin-4-yl]-N-phenylpropanamide	256945: Displacement of [3H]DAMGO from recombinant human mu opioid receptor	ki	0.0001	uM
(1R,9R,10S)-17-(cyclopropylmethyl)-3,10-dihydroxy-13-oxo-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene-4-carboxamide	238974: Binding affinity against Opioid receptor mu 1 expressed in CHO cells using [3H]DAMGO as radioligand	ki	0.0001	uM
(1S,2S,10R,18R)-8-(cyclohexylmethyl)-19-(cyclopropylmethyl)-2,13-dihydroxy-11-oxa-8,19-diazahexacyclo[10.9.1.01,10.02,18.04,9.016,22]docosa-4(9),12,14,16(22)-tetraen-7-one	1181414: Displacement of [3H]DAMGO from human recombinant mu opioid receptor expressed in CHO cell membranes after 60 mins by scintillation counting method	ki	0.0001	uM
(2R)-2-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-N-[(4S)-2-(3-amino-3-oxopropyl)-3-oxo-4,5-dihydro-1H-2-benzazepin-4-yl]-5-(diaminomethylideneamino)pentanamide	1302008: Displacement of [3H]diprenorphine from human mu opioid receptor expressed in HEK293 cell membrane incubated for 1 hr by TopCount scintillation counting method	ki	0.0001	uM
(2S)-1-[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pyrrolidine-2-carboxamide	1409273: Agonist activity at human MOR expressed in CHO cell membranes after 60 mins by [35S]GTPgammaS binding assay	ec50	0.0001	uM
(2S)-1-[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]-N-[(2S)-1-[[(1S)-2-carbamoyl-1-thiophen-2-ylprop-2-enyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pyrrolidine-2-carboxamide	1252985: Agonist activity at mu opioid receptor (unknown origin) transfected in HEK293 cells assessed as inhibition of forskolin-stimulated cAMP production	ec50	0.0001	uM
(2S)-1-[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]-N-[(2S)-1-[[(1S)-2-carbamoyl-1-thiophen-3-ylprop-2-enyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pyrrolidine-2-carboxamide	1252985: Agonist activity at mu opioid receptor (unknown origin) transfected in HEK293 cells assessed as inhibition of forskolin-stimulated cAMP production	ec50	0.0001	uM
(2S)-6-amino-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]hexanamide	1872031: Binding affinity to MOP (unknown origin)	ki	0.0001	uM
4-[(R)-[(2S,5R)-2,5-dimethyl-4-prop-2-enylpiperazin-1-yl]-(3-methoxyphenyl)methyl]-N,N-diethylbenzamide	1137721: Agonist activity at human mu opioid receptor expressed in HEK293 cells by CellKey method	ec50	0.0001	uM
N-[4-(methoxymethyl)-1-(2-phenylethyl)piperidin-4-yl]-N-phenylpropanamide	150845: Binding affinity against Opioid receptor mu 1	ki	0.0001	uM
4-[4-[4-chloro-3-(trifluoromethyl)phenyl]-4-hydroxypiperidin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide	239449: Binding affinity for recombinant human mu-opioid receptor was determined by using [3H]- diprenophine radioligand	ki	0.0001	uM
3-[(1R,5R)-8-[(4-tert-butylphenyl)methyl]-8-azabicyclo[3.2.1]octan-3-yl]benzamide	1467158: Displacement of [3H]DPN from recombinant human mu opioid receptor expressed in CHOK1 cell membranes	ki	0.0001	uM
3-[(1R,5R)-8-(3-phenylpropyl)-8-azabicyclo[3.2.1]octan-3-yl]benzamide	1467158: Displacement of [3H]DPN from recombinant human mu opioid receptor expressed in CHOK1 cell membranes	ki	0.0001	uM
3-[(1R,5R)-8-(3-phenoxypropyl)-8-azabicyclo[3.2.1]octan-3-yl]phenol	1467158: Displacement of [3H]DPN from recombinant human mu opioid receptor expressed in CHOK1 cell membranes	ki	0.0001	uM
3-[(1R,5R)-8-[(4-tert-butylphenyl)methyl]-8-azabicyclo[3.2.1]octan-3-yl]phenol	1467158: Displacement of [3H]DPN from recombinant human mu opioid receptor expressed in CHOK1 cell membranes	ki	0.0001	uM
1-cyclohexyl-2-[(1R,5R)-3-(3-hydroxyphenyl)-8-azabicyclo[3.2.1]octan-8-yl]ethanone	1467158: Displacement of [3H]DPN from recombinant human mu opioid receptor expressed in CHOK1 cell membranes	ki	0.0001	uM
3-[(1R,5R)-8-(3-phenylpropyl)-8-azabicyclo[3.2.1]octan-3-yl]phenol	1467158: Displacement of [3H]DPN from recombinant human mu opioid receptor expressed in CHOK1 cell membranes	ki	0.0001	uM
3-[(1S,5R)-8-[2-[acetyl(cyclohexylmethyl)amino]ethyl]-8-azabicyclo[3.2.1]octan-3-yl]benzamide	1611793: Displacement of [3H]-DPN from recombinant human mu opioid receptor expressed in CHO-K1 cell membranes by radioligand binding assay	ki	0.0001	uM
N-[2-[(1R,5S)-3-(3-carbamoylphenyl)-8-azabicyclo[3.2.1]octan-8-yl]ethyl]-N-(cyclohexylmethyl)furan-2-carboxamide	1611793: Displacement of [3H]-DPN from recombinant human mu opioid receptor expressed in CHO-K1 cell membranes by radioligand binding assay	ki	0.0001	uM
methyl N-[2-[(1S,5R)-3-(3-carbamoylphenyl)-8-azabicyclo[3.2.1]octan-8-yl]ethyl]-N-(cyclohexylmethyl)carbamate	1611793: Displacement of [3H]-DPN from recombinant human mu opioid receptor expressed in CHO-K1 cell membranes by radioligand binding assay	ki	0.0001	uM
3-[(1S,5R)-8-[2-[cyclohexylmethyl(2,2-dimethylpropanoyl)amino]ethyl]-8-azabicyclo[3.2.1]octan-3-yl]benzamide	1611793: Displacement of [3H]-DPN from recombinant human mu opioid receptor expressed in CHO-K1 cell membranes by radioligand binding assay	ki	0.0001	uM
(4R,4aS,7aR,12bR)-4a-[3-(4-chlorophenyl)propylamino]-3-(cyclopropylmethyl)-9-methoxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one	273141: Activity at human recombinant mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTP-gamma-S binding	ic50	0.0001	uM

CTD chemical–gene interactions

60 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Morphine	decreases reaction, decreases activity, increases expression, increases phosphorylation, decreases response to substance (+7 more)	11
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-	decreases reaction, increases activity, affects binding, affects reaction, increases phosphorylation (+1 more)	6
mitragynine	affects reaction, increases activity, decreases reaction, increases expression, affects binding	3
Naloxone	decreases activity, increases expression, decreases reaction, increases activity, affects binding (+1 more)	3
isotonitazene	affects binding, decreases reaction, increases activity	2
carfentanil	affects binding, decreases reaction, affects reaction	2
nalmefene	affects binding, decreases activity, increases expression	2
alvimopan	affects binding, decreases activity	2
7-hydroxymitragynine	affects binding, affects reaction, increases activity	2
Buprenorphine	affects activity, affects binding, increases activity, decreases reaction	2
Butorphanol	affects activity, increases activity	2
Cocaine	affects reaction, increases response to substance, affects binding	2
Fentanyl	increases activity, increases phosphorylation, affects binding	2
Naltrexone	affects binding, affects cotreatment, decreases activity, increases expression, affects response to substance	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
GUM1 compound	increases activity	1
brorphine	increases activity	1
chlornaltrexamine	affects binding, affects localization, decreases activity, increases expression	1
sodium arsenite	affects methylation	1
beta-funaltrexamine	affects binding, decreases reaction, increases activity	1
aflatoxin B2	decreases methylation	1
methylnaltrexone	affects binding	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
tianeptine	increases activity	1
clocinnamox	decreases activity, increases expression, affects binding, affects localization	1
7-benzylidenenaltrexone	affects binding, affects localization, decreases activity, increases expression	1
cyclorphan	affects binding	1
CGP 52608	increases reaction, affects binding	1
iodopravadoline	decreases reaction, increases expression	1
JHW 015	increases expression	1

ChEMBL screening assays

2593 unique, capped per target: 1649 binding, 888 functional, 40 admet, 11 toxicity, 5 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1794484	Functional	PUBCHEM_BIOASSAY: Luminescence-based cell-based high throughput dose response assay for agonists of heterodimerization of the mu 1 (OPRM1) and delta 1 (OPRD1) opioid receptors. (Class of assay: confirmatory) [Related pubchem assays (deposit	PubChem BioAssay data set
CHEMBL4145313	Binding	Displacement of [3H]-diprenorphine from human mu-delta opioid receptor heterodimer expressed in CHO cell membranes at high site fraction after 80 mins by scintillation counting analysis relative to control	Synthesis and Evaluation of a Novel Bivalent Selective Antagonist for the Mu-Delta Opioid Receptor Heterodimer that Reduces Morphine Withdrawal in Mice. — J Med Chem
CHEMBL3239402	ADMET	Agonist activity at GFP-fused mu opioid receptor (unknown origin) expressed in HEK293 cells assessed as recruitment of beta-arrestin-2 after 10 mins by BRET assay	Endomorphin analogues with mixed μ-opioid (MOP) receptor agonism/δ-opioid (DOP) receptor antagonism and lacking β-arrestin2 recruitment activity. — Bioorg Med Chem

Cellosaurus cell lines

12 cell lines: 7 cancer cell line, 4 spontaneously immortalized cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8LU	Abcam HCT 116 OPRM1 KO	Cancer cell line	Male
CVCL_B8ZS	Abcam MCF-7 OPRM1 KO	Cancer cell line	Female
CVCL_B9P0	Abcam A-549 OPRM1 KO	Cancer cell line	Male
CVCL_C0TE	ACTOne OPRM1	Transformed cell line	Female
CVCL_F2AL	CHO-K1 (+Galpha16) AequoScreen Opioid Mu (OP3)	Spontaneously immortalized cell line	Female
CVCL_H486	CHO-K1/OPRM1/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV62	cAMP Hunter CHO-K1 OPRM1 Gi	Spontaneously immortalized cell line	Female
CVCL_KY70	PathHunter CHO-K1 OPRM1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LB00	PathHunter U2OS OPRM1 beta-arrestin	Cancer cell line	Female
CVCL_LB01	PathHunter U2OS OPRM1 beta-arrestin-1	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.