OPRM1
Basic information
Region (hg38): 6:154010496-154246867
Links
Phenotypes
GenCC
Source:
ClinVar
This is a list of variants' phenotypes submitted to
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 | 4 | |||||
missense | 23 | 26 | ||||
nonsense | 1 | |||||
start loss | 0 | |||||
frameshift | 0 | |||||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 0 | |||||
splice region | 0 | |||||
non coding | 7 | |||||
Total | 0 | 0 | 27 | 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:
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:
- 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
- ghis
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