OPRM1

opioid receptor mu 1, the group of Opioid receptors

Basic information

Region (hg38): 6:154010495-154246867

Links

ENSG00000112038 ∙ NCBI:4988 ∙ OMIM:600018 ∙ HGNC:8156 ∙ Uniprot:P35372 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OPRM1 gene.

• Inborn genetic diseases (22 variants)
• not provided (8 variants)
• Tramadol response (4 variants)
• not specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OPRM1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	1	4
missense			16	2	1	19
nonsense					1	1
start loss						0
frameshift						0
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			4	1	2	7
Total	0	0	20	7	5

Variants in OPRM1

This is a list of pathogenic ClinVar variants found in the OPRM1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-154010592-A-C		Tramadol response	drug response (Apr 28, 2018)
6-154010635-T-A		Tramadol response	drug response (Apr 28, 2018)
6-154010661-A-G		Tramadol response	drug response (Apr 28, 2018)
6-154010665-G-A		Tramadol response	drug response (Apr 28, 2018)
6-154010715-G-A		Tramadol response	drug response (Apr 28, 2018)
6-154010718-T-A		Tramadol response	drug response (Apr 28, 2018)
6-154010744-GC-G		Tramadol response	drug response (Apr 28, 2018)
6-154010760-A-G		Tramadol response	drug response (Apr 28, 2018)
6-154010825-C-T		Tramadol response	drug response (Apr 28, 2018)
6-154010828-G-A		Tramadol response	drug response (Apr 28, 2018)
6-154010829-C-T		Tramadol response	drug response (Apr 28, 2018)
6-154010840-A-T		Tramadol response	drug response (Apr 28, 2018)
6-154010917-CA-C		Tramadol response	drug response (Apr 28, 2018)
6-154010958-CCT-C		Tramadol response	drug response (Apr 28, 2018)
6-154010964-A-T		Tramadol response	drug response (Apr 28, 2018)
6-154011008-C-T		Tramadol response	drug response (Apr 28, 2018)
6-154011017-G-T		Tramadol response	drug response (Apr 28, 2018)
6-154011029-G-T		Tramadol response	drug response (Apr 28, 2018)
6-154011069-G-T		Tramadol response	drug response (Apr 28, 2018)
6-154011088-G-C		Tramadol response	drug response (Apr 28, 2018)
6-154011103-CAT-C		Tramadol response	drug response (Apr 28, 2018)
6-154039031-C-A		Tramadol response	drug response (Apr 28, 2018)
6-154039033-T-C		Tramadol response	drug response (Apr 28, 2018)
6-154039035-C-A		Tramadol response	drug response (Apr 28, 2018)
6-154039038-G-A		Tramadol response	drug response (Apr 28, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OPRM1	protein_coding	protein_coding	ENST00000434900	5	236371

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.89e-11	0.143	125016	1	200	125217	0.000803

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.619	311	282	1.10	0.0000142	3202
Missense in Polyphen		119	104.16	1.1425		1277
Synonymous	-0.491	117	110	1.06	0.00000561	1010
Loss of Function	0.526	17	19.5	0.871	0.00000122	186

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00130	0.00128
Ashkenazi Jewish	0.00179	0.00169
East Asian	0.00	0.00
Finnish	0.000606	0.000602
European (Non-Finnish)	0.000269	0.000264
Middle Eastern	0.00	0.00
South Asian	0.00364	0.00353
Other	0.000504	0.000492

dbNSFP

Source: dbNSFP

• Function: 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 (PubMed:7905839, PubMed:7957926, PubMed:7891175, PubMed:12589820, PubMed:9689128). 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 (PubMed:7905839). 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 (PubMed:12068084). 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 whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects (PubMed:20525224). Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity (PubMed:16580639). {ECO:0000250|UniProtKB:P33535, ECO:0000250|UniProtKB:P42866, ECO:0000269|PubMed:10529478, ECO:0000269|PubMed:12068084, ECO:0000269|PubMed:12589820, ECO:0000269|PubMed:16580639, ECO:0000269|PubMed:20525224, ECO:0000269|PubMed:7891175, ECO:0000269|PubMed:7905839, ECO:0000269|PubMed:7957926, ECO:0000269|PubMed:9689128, ECO:0000303|PubMed:10836142, ECO:0000303|PubMed:19300905}.
• Pathway: Estrogen signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Levomethadyl Acetate Action Action Pathway;Fluoxetine Action Pathway;Citalopram Action Pathway;Escitalopram Action Pathway;Imipramine Action Pathway;Desipramine Action Pathway;Levallorphan Action Pathway;Dimethylthiambutene Action Pathway;Ethylmorphine Action Pathway;Pentazocine Action Pathway;Naltrexone Action Pathway;Buprenorphine Action Pathway;Alvimopan Action Pathway;Naloxone Action Pathway;Dihydromorphine Action Pathway;Methadone Metabolism Pathway;Codeine Metabolism Pathway;Morphine Metabolism Pathway;Heroin Metabolism Pathway;Nicotine Action Pathway;Nalbuphine Action Pathway;Ketobemidone Action Pathway;Lidocaine (Local Anaesthetic) Action Pathway;Mepivacaine Action Pathway;Chloroprocaine Action Pathway;Cocaine Action Pathway;Dibucaine Action Pathway;Levobupivacaine Action Pathway;Benzocaine Action Pathway;Bupivacaine Action Pathway;Levorphanol Action Pathway;Propoxyphene Action Pathway;Tramadol Action Action Pathway;Diphenoxylate Action Pathway;Anileridine Action Pathway;Methadone Action Pathway;Oxycodone Action Pathway;Oxybuprocaine Action Pathway;Prilocaine Action Pathway;Procaine Action Pathway;Proparacaine Action Pathway;Ropivacaine Action Pathway;Codeine Action Pathway;Morphine Action Pathway;Heroin Action Pathway;Alfentanil Action Pathway;Oxymorphone Action Pathway;Hydrocodone Action Pathway;Hydromorphone Action Pathway;Sufentanil Action Pathway;Remifentanil Action Pathway;Fentanyl Action Pathway;Carfentanil Action Pathway;3-Methylthiofentanyl Action Pathway;Methadyl Acetate Action Pathway;Dezocine Action Pathway;Peptide GPCRs;Interleukin-4 and 13 signaling;GPCRs, Class A Rhodopsin-like;T-Cell antigen Receptor (TCR) Signaling Pathway;Signaling by GPCR;Signal Transduction;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G-protein activation;Opioid Signalling;G alpha (i) signalling events;GPCR downstream signalling;IL4-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.280

Intolerance Scores

• loftool: 0.936
• rvis_EVS: 1.91
• rvis_percentile_EVS: 97.43

Haploinsufficiency Scores

• pHI: 0.171
• hipred: N
• hipred_score: 0.453

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.654

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Oprm1
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype

Zebrafish Information Network

• Gene name: oprm1
• Affected structure: optic tectum
• Phenotype tag: abnormal
• Phenotype quality: increased process quality

Gene ontology

• Biological process: acute inflammatory response to antigenic stimulus;G protein-coupled receptor signaling pathway;G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger;adenylate cyclase-activating dopamine receptor signaling pathway;negative regulation of adenylate cyclase activity;phospholipase C-activating G protein-coupled receptor signaling pathway;neuropeptide signaling pathway;sensory perception;locomotory behavior;negative regulation of cell population proliferation;response to radiation;cytokine-mediated signaling pathway;sensory perception of pain;adenylate cyclase-inhibiting opioid receptor signaling pathway;response to food;positive regulation of appetite;response to lipopolysaccharide;opioid receptor signaling pathway;wound healing;response to cocaine;eating behavior;estrous cycle;behavioral response to ethanol;positive regulation of neurogenesis;regulation of sensory perception of pain;excitatory postsynaptic potential;negative regulation of Wnt protein secretion;positive regulation of ERK1 and ERK2 cascade;calcium ion transmembrane transport;response to growth factor;cellular response to morphine;regulation of cellular response to stress;negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway;regulation of NMDA receptor activity
• Cellular component: endosome;endoplasmic reticulum;Golgi apparatus;plasma membrane;integral component of plasma membrane;focal adhesion;axon;dendrite;dendrite membrane;dendrite cytoplasm;sarcolemma;perikaryon;membrane raft;spine apparatus;integral component of postsynaptic membrane;integral component of presynaptic membrane
• Molecular function: G-protein alpha-subunit binding;G protein-coupled receptor activity;beta-endorphin receptor activity;voltage-gated calcium channel activity;protein binding;protein C-terminus binding;protein domain specific binding;filamin binding;G-protein beta-subunit binding;morphine receptor activity;peptide binding;neuropeptide binding