OPRM1 (Mu-type opioid receptor) variants and mutations
OPRM1 (also known as Mu-type opioid receptor) is a human protein-coding gene encoding a mu-type opioid receptor protein. A G protein-coupled receptor for endogenous opioids and medicines such as morphine and fentanyl. Its activation changes neuronal signaling involved in pain, reward, and respiratory control through inhibitory G protein pathways. This analysis covers 924 OPRM1 variants and mutations. Of these, 74% have computational variant effect predictions. Disease context includes opiate dependence, Pain, and opioid use disorder. Example OPRM1 variants include M1?, M1V, and M1T.
Variant analysis overview
- Gene: OPRM1
- Protein: Mu-type opioid receptor
- UniProt accession: P35372
- Organism: Homo sapiens
- Variants analyzed: 924
- Variant scope: all variants
- Completed: 2026-07-23
Variant and mutation evidence
- Variant composition: 670 unspecified-consequence records; 152 missense variants; 64 synonymous variants; 25 frameshift variants; 3 splice-region variants; 2 in-frame deletions; 6 stop-gained variants; 2 in-frame insertions
- Prediction scores: 685 variants have prediction scores (74% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: opiate dependence, Pain, opioid use disorder, cancer, alcohol dependence, Chronic pain, drug dependence, Diarrhea, migraine disorder, Constipation, major depressive disorder, osteoarthritis.
Protein structure and variant hotspots
- Protein features: 7 transmembrane segments; 10 post-translational modification sites.
- Structural context: 284 variants have structural context.
- PTM context: 31 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable OPRM1 variants
Examples include M1?, M1V, M1T, M1I, D2E, D2G, S3G, S3I. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10000, Variant assessed as somatic; high impact.
- M1V (p.Met1Val), gnomAD 6-154010516-A-G, CADD 5.53, SIFT 0.15
- M1T (p.Met1Thr), rs754157819, gnomAD 6-154010517-T-C, CADD 0.38, SIFT 0.04
- M1I (p.Met1Ile), gnomAD 6-154010518-G-A, CADD 1.95, SIFT 0.25
- D2E (p.Asp2Glu), Ensembl rs2128393831
- D2G (p.Asp2Gly), gnomAD 6-154039365-GATGC, CADD 11.80
- S3G (p.Ser3Gly), rs747772652, ClinGen CA366152276, ClinVar RCV001029185, ExAC rs747772652, drug response, Tramadol response
- S3I (p.Ser3Ile), cosmic curated COSV57674
- S3R (p.Ser3Arg), cosmic curated COSV57678, ExAC rs747772652, REVEL 0.27, CADD 24.80, Drug response
- S3A (p.Ser3Ala), rs2128393339, gnomAD 6-154039362-T-G, CADD 5.18, SIFT 0.00
- S3S (p.Ser3Ser), gnomAD 6-154039364-A-G, CADD 13.70
- S4S (p.Ser4Ser), rs755001511, gnomAD 6-154010530-C-T, CADD 9.84
- p.Ser4dup, gnomAD 6-154039549-A-ACA, CADD 19.20
- A5S (p.Ala5Ser), TOPMed rs1223121173, gnomAD rs1223121173, REVEL 0.06, CADD 0.02, Likely benign
- A5T (p.Ala5Thr), rs1223121173, ClinGen CA366152290, cosmic curated COSV10000, ClinVar RCV004237635, REVEL 0.05, CADD 0.02, Likely benign, not specified
- A5D (p.Ala5Asp), gnomAD 6-154010523-C-A, CADD 6.10, SIFT 0.50
- A5V (p.Ala5Val), rs36041553, gnomAD 6-154010523-C-T, CADD 8.80, SIFT 0.14
- A5P (p.Ala5Pro), rs1478091618, gnomAD 6-154039368-G-C, CADD 13.30, SIFT 0.00
- A5L (p.Ala5Leu), gnomAD 6-154039556-CG-C, CADD 7.46
- A5A (p.Ala5Ala), gnomAD 6-154039559-T-G, CADD 4.92
- A6D (p.Ala6Asp), 1000Genomes rs1799972, ESP rs1799972, ExAC rs1799972, TOPMed rs1799972, REVEL 0.09, CADD 7.35
- A6G (p.Ala6Gly), 1000Genomes rs1799972, ESP rs1799972, ExAC rs1799972, TOPMed rs1799972, REVEL 0.04, CADD 0.03
- A6V (p.Ala6Val), rs1799972, cosmic curated COSV57676, UniProt VAR 009525, 1000Genomes rs1799972, REVEL 0.05, CADD 0.05
- A6T (p.Ala6Thr), gnomAD 6-154039560-G-A, REVEL 0.08, MetaLR 0.01
- A6A (p.Ala6Ala), rs1487920320, gnomAD 6-154039562-C-T, CADD 2.88
- P7H (p.Pro7His), rs777099271, NCI-TCGA Cosmic COSV1000, ExAC rs777099271, TOPMed rs777099271, REVEL 0.24, CADD 19.80, Variant assessed as somatic; moderate impact.
- P7L (p.Pro7Leu), rs777099271, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10000, ExAC rs777099271, REVEL 0.21, CADD 16.10, Variant assessed as somatic; moderate impact.
- P7T (p.Pro7Thr), cosmic curated COSV10506
- P7A (p.Pro7Ala), rs1777671868, gnomAD 6-154010552-C-G, CADD 13.90, SIFT 0.51
- P7R (p.Pro7Arg), rs1360351993, gnomAD 6-154010553-C-G, CADD 12.50, SIFT 0.35
- P7P (p.Pro7Pro), rs1304457561, gnomAD 6-154010554-C-G, CADD 12.90
- P7S (p.Pro7Ser), rs774041245, gnomAD 6-154039182-C-T, CADD 7.68, SIFT 0.00
- T8A (p.Thr8Ala), TOPMed rs1422558678, REVEL 0.03, CADD 0.00
- T8K (p.Thr8Lys), gnomAD rs1779597786, REVEL 0.03, CADD 0.56
- T8P (p.Thr8Pro), TOPMed rs1422558678
- T8R (p.Thr8Arg), NCI-TCGA TCGA novel, gnomAD rs1779597786, REVEL 0.04, CADD 0.34, Variant assessed as somatic; high impact.
- T8S (p.Thr8Ser), TOPMed rs1422558678, REVEL 0.03, CADD 0.00
- T8T (p.Thr8Thr), rs1320176621, gnomAD 6-154010539-C-T, CADD 10.50
- T8H (p.Thr8His), rs1554256936, gnomAD 6-154039560-G-GC, CADD 22.20
- T8M (p.Thr8Met), gnomAD 6-154039567-C-T, REVEL 0.08, MetaLR 0.01
- N9D (p.Asn9Asp), gnomAD rs1187761291, REVEL 0.14, CADD 13.20
- N9K (p.Asn9Lys), rs745863104, ExAC rs745863104, TOPMed rs745863104, gnomAD rs745863104, REVEL 0.12, CADD 8.30, Uncertain significance, not specified
- N9S (p.Asn9Ser), gnomAD 6-154039570-A-G, REVEL 0.04, MetaLR 0.01
- N9N (p.Asn9Asn), rs745863104, gnomAD 6-154039571-C-T, CADD 1.25
- A10D (p.Ala10Asp), ExAC rs763117342, gnomAD rs763117342, REVEL 0.22, CADD 15.20
- A10S (p.Ala10Ser), NCI-TCGA Cosmic COSV5767, cosmic curated COSV57672, Variant assessed as somatic; moderate impact.
- A10T (p.Ala10Thr), TOPMed rs1425495037, gnomAD rs1425495037, REVEL 0.06, CADD 6.27, Uncertain significance, not specified
- A10V (p.Ala10Val), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10000, Variant assessed as somatic; moderate impact.
- A10P (p.Ala10Pro), rs1407159964, gnomAD 6-154010543-G-C, CADD 6.42, SIFT 0.13
- A10A (p.Ala10Ala), gnomAD 6-154010545-T-C, CADD 17.80
- S11G (p.Ser11Gly), TOPMed rs1779600996, gnomAD rs1779600996, REVEL 0.04, CADD 7.56
- S11N (p.Ser11Asn), gnomAD 6-154010535-G-A, CADD 11.40, SIFT 0.70
- S11A (p.Ser11Ala), gnomAD 6-154010555-T-G, CADD 15.30, SIFT 0.57
- S11S (p.Ser11Ser), rs1282865787, gnomAD 6-154010557-C-T, CADD 20.40
- S11C (p.Ser11Cys), rs760717655, gnomAD 6-154039402-C-G, CADD 10.70, SIFT 0.00
- S11F (p.Ser11Phe), gnomAD 6-154039402-C-T, CADD 10.90, SIFT 0.00
- S11Y (p.Ser11Tyr), gnomAD 6-154039402-C-A, CADD 10.40, SIFT 0.00
- S11R (p.Ser11Arg), gnomAD 6-154039575-A-C, REVEL 0.19, MetaLR 0.02
- S11K (p.Ser11Lys), rs1175639223, gnomAD 6-154039575-AGC-A, CADD 24.70
- N12I (p.Asn12Ile), Ensembl rs199645285, REVEL 0.20, CADD 22.00
- N12K (p.Asn12Lys), cosmic curated COSV10874
- N12S (p.Asn12Ser), rs199645285, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10000, Ensembl rs199645285, REVEL 0.14, CADD 19.00, Variant assessed as somatic; moderate impact.
- N12T (p.Asn12Thr), rs919460100, gnomAD 6-154039222-A-C, CADD 22.70, SIFT 0.00
- N12D (p.Asn12Asp), gnomAD 6-154039578-A-G, REVEL 0.07, MetaLR 0.01
- C13G (p.Cys13Gly), ExAC rs76181157, gnomAD rs76181157, REVEL 0.24, CADD 23.10
- C13W (p.Cys13Trp), TOPMed rs200776506, REVEL 0.27, CADD 23.90
- C13S (p.Cys13Ser), gnomAD 6-154039165-G-C, CADD 12.90, SIFT 0.00
- C13Y (p.Cys13Tyr), rs1178178686, gnomAD 6-154039165-G-A, CADD 14.30, SIFT 0.00
- C13R (p.Cys13Arg), gnomAD 6-154039581-T-C, REVEL 0.24, MetaLR 0.03
- C13C (p.Cys13Cys), rs200776506, gnomAD 6-154039583-C-T, CADD 8.67
- T14A (p.Thr14Ala), TOPMed rs894934906, gnomAD rs894934906, REVEL 0.12, CADD 15.30, Uncertain significance, not specified
- T14I (p.Thr14Ile), NCI-TCGA Cosmic COSV1000, Variant assessed as somatic; moderate impact.
- T14N (p.Thr14Asn), cosmic curated COSV10000
- T14S (p.Thr14Ser), gnomAD rs1457556221, REVEL 0.07, CADD 6.77, Likely benign, not specified
- T14P (p.Thr14Pro), rs1473274739, gnomAD 6-154039392-A-C, CADD 13.60, SIFT 0.01
- T14R (p.Thr14Arg), rs200040051, gnomAD 6-154039393-C-G, CADD 12.90, SIFT 0.00
- T14M (p.Thr14Met), rs200040051, gnomAD 6-154039393-C-T, CADD 13.30, SIFT 0.00
- T14T (p.Thr14Thr), gnomAD 6-154039418-T-A, CADD 6.91
- D15H (p.Asp15His), ExAC rs774232469, TOPMed rs774232469, gnomAD rs774232469, REVEL 0.26, CADD 22.80
- D15N (p.Asp15Asn), gnomAD 6-154039206-G-A, CADD 14.50, SIFT 0.00
- A16G (p.Ala16Gly), ExAC rs767553433, TOPMed rs767553433, gnomAD rs767553433, REVEL 0.14, CADD 11.30
- A16S (p.Ala16Ser), ESP rs367637070, ExAC rs367637070, TOPMed rs367637070, gnomAD rs367637070, REVEL 0.07, CADD 3.39
- A16T (p.Ala16Thr), ESP rs367637070, ExAC rs367637070, TOPMed rs367637070, gnomAD rs367637070, REVEL 0.04, CADD 5.69
- A16V (p.Ala16Val), ExAC rs767553433, TOPMed rs767553433, gnomAD rs767553433, REVEL 0.23, CADD 12.10
- A16P (p.Ala16Pro), gnomAD 6-154039590-G-C, REVEL 0.04, MetaLR 0.01
- L17S (p.Leu17Ser), gnomAD 6-154039168-T-C, CADD 10.10, SIFT 0.36
- L17W (p.Leu17Trp), gnomAD 6-154039200-TC-T, CADD 22.00
- L17V (p.Leu17Val), rs1779519298, gnomAD 6-154039203-T-G, CADD 14.10, SIFT 0.87
- L17F (p.Leu17Phe), gnomAD 6-154039205-G-T, CADD 13.50, SIFT 0.03
- L17P (p.Leu17Pro), rs1368045511, gnomAD 6-154039231-T-C, CADD 14.90, SIFT 0.00
- L17L (p.Leu17Leu), rs1779545832, gnomAD 6-154039376-C-T, CADD 4.26
- L17I (p.Leu17Ile), rs1779552356, gnomAD 6-154039395-C-A, CADD 15.30, SIFT 0.00
- A18G (p.Ala18Gly), 1000Genomes rs577345039, ExAC rs577345039, TOPMed rs577345039, gnomAD rs577345039, REVEL 0.06, CADD 6.70, Drug response
- A18T (p.Ala18Thr), ESP rs111339162, ExAC rs111339162, TOPMed rs111339162, gnomAD rs111339162, REVEL 0.02, CADD 0.42, Likely benign, not specified
- A18V (p.Ala18Val), rs577345039, ClinGen CA4061360, cosmic curated COSV57674, ClinVar RCV001029183, CADD 15.60, drug response, Tramadol response
- A18E (p.Ala18Glu), gnomAD 6-154039216-C-A, CADD 23.10, SIFT 0.00
- A18A (p.Ala18Ala), rs760385507, gnomAD 6-154039217-G-A, CADD 13.60
- A18D (p.Ala18Asp), gnomAD 6-154039411-C-A, CADD 14.60, SIFT 0.03
- Y19* (p.Tyr19Ter), gnomAD rs1779608711, CADD 33.00
- Y19H (p.Tyr19His), cosmic curated COSV57673, REVEL 0.13, CADD 6.46
- Y19S (p.Tyr19Ser), gnomAD 6-154039197-TA-T, CADD 18.40
- Y19C (p.Tyr19Cys), gnomAD 6-154039198-A-G, CADD 10.60, SIFT 0.11
- Y19Y (p.Tyr19Tyr), rs767580587, gnomAD 6-154039199-C-T, CADD 2.32
- Y19L (p.Tyr19Leu), gnomAD 6-154039597-CGT-C, CADD 21.10
- S20Q (p.Ser20Gln), gnomAD 6-154039600-AC-A, CADD 17.50
- S20* (p.Ser20Ter), gnomAD 6-154039603-C-G, CADD 35.00
- S20L (p.Ser20Leu), gnomAD 6-154039603-C-T, REVEL 0.22, MetaLR 0.01
- S21G (p.Ser21Gly), ExAC rs757930794, TOPMed rs757930794, gnomAD rs757930794, REVEL 0.03, CADD 20.80
- S21R (p.Ser21Arg), ExAC rs757930794, TOPMed rs757930794, gnomAD rs757930794, REVEL 0.23, CADD 18.60
- S21V (p.Ser21Val), rs753892000, gnomAD 6-154039603-CA-C, CADD 19.90
- C22G (p.Cys22Gly), rs1159118686, gnomAD 6-154039425-T-G, CADD 14.80, SIFT 0.03
- C22S (p.Cys22Ser), gnomAD 6-154039426-G-C, CADD 15.20, SIFT 0.03
- C22Y (p.Cys22Tyr), rs776522590, gnomAD 6-154039426-G-A, CADD 15.80, SIFT 0.01
- C22F (p.Cys22Phe), gnomAD 6-154039426-G-T, CADD 16.10, SIFT 0.02
- C22C (p.Cys22Cys), rs1779611149, gnomAD 6-154039610-C-T, CADD 11.70
- S23F (p.Ser23Phe), ExAC rs201728064, REVEL 0.20, CADD 21.20
- S23P (p.Ser23Pro), ExAC rs777485603, TOPMed rs777485603, gnomAD rs777485603, REVEL 0.13, CADD 15.50, Uncertain significance, not specified
- S23S (p.Ser23Ser), gnomAD 6-154039613-C-G, CADD 8.65
- P24H (p.Pro24His), rs1308502469, gnomAD 6-154039223-TC-T, CADD 26.90
- P24A (p.Pro24Ala), gnomAD 6-154039224-C-G, CADD 19.40, SIFT 0.00
- P24R (p.Pro24Arg), gnomAD 6-154039225-C-G, CADD 22.20, SIFT 0.00
- P24Q (p.Pro24Gln), gnomAD 6-154039225-C-A, CADD 22.40, SIFT 0.00
- P24P (p.Pro24Pro), rs1446108001, gnomAD 6-154039226-A-G, CADD 11.70
- A25E (p.Ala25Glu), rs1583172139, ClinGen CA366152407, ClinVar RCV001029182, Ensembl rs1583172139, drug response, Tramadol response
- A25T (p.Ala25Thr), ExAC rs756777151, gnomAD rs756777151, REVEL 0.26, CADD 21.60
- A25S (p.Ala25Ser), gnomAD 6-154039254-G-T, CADD 18.40, SIFT 0.00
- A25G (p.Ala25Gly), rs1049355494, gnomAD 6-154039255-C-G, CADD 7.58, SIFT 0.00
- A25A (p.Ala25Ala), rs1432478155, gnomAD 6-154039256-C-T, CADD 6.27
- A25V (p.Ala25Val), gnomAD 6-154039273-C-T, CADD 2.65, SIFT 0.01
- A25D (p.Ala25Asp), gnomAD 6-154039273-C-A, CADD 2.94, SIFT 0.00
- A25P (p.Ala25Pro), rs199671121, gnomAD 6-154039278-G-C, CADD 4.07, SIFT 0.52
- P26L (p.Pro26Leu), cosmic curated COSV10000, CADD 15.10
- P26A (p.Pro26Ala), gnomAD 6-154039236-C-G, CADD 1.37, SIFT 0.05
- P26S (p.Pro26Ser), rs1779523015, gnomAD 6-154039236-C-T, CADD 2.95, SIFT 0.95
- P26P (p.Pro26Pro), rs753987987, gnomAD 6-154039238-T-C, CADD 4.14
- S27I (p.Ser27Ile), ExAC rs780726314, gnomAD rs780726314, REVEL 0.24, CADD 17.80
- S27T (p.Ser27Thr), gnomAD 6-154039623-AG-A, CADD 22.90
- S27R (p.Ser27Arg), gnomAD 6-154039625-C-A, REVEL 0.25, MetaLR 0.07
- P28A (p.Pro28Ala), gnomAD rs1207812281, CADD 14.60
- P28H (p.Pro28His), ExAC rs745771363
- P28S (p.Pro28Ser), NCI-TCGA Cosmic COSV5768, cosmic curated COSV57687, CADD 15.60, Variant assessed as somatic; moderate impact.
- P28L (p.Pro28Leu), rs929536552, gnomAD 6-154039243-C-T, CADD 16.80, SIFT 0.00
- P28P (p.Pro28Pro), rs1326586132, gnomAD 6-154039244-C-T, CADD 7.85
- P28T (p.Pro28Thr), rs1031653190, gnomAD 6-154039612-C-CCC, CADD 23.60
- G29C (p.Gly29Cys), cosmic curated COSV57677, gnomAD rs775097209, REVEL 0.20, CADD 19.00
- G29S (p.Gly29Ser), gnomAD rs775097209
- G29R (p.Gly29Arg), rs1454907521, gnomAD 6-154010546-G-A, CADD 15.90, SIFT 0.35
- G29G (p.Gly29Gly), rs1562365567, gnomAD 6-154010548-G-A, CADD 15.60
- G29A (p.Gly29Ala), gnomAD 6-154039378-G-C, CADD 2.44, SIFT 0.01
- G29V (p.Gly29Val), rs1352307794, gnomAD 6-154039420-G-T, CADD 13.80, SIFT 0.00
- S30F (p.Ser30Phe), TOPMed rs1779617432, REVEL 0.16, CADD 23.00
- S30Y (p.Ser30Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S30S (p.Ser30Ser), rs1779524626, gnomAD 6-154039247-C-T, CADD 7.27
- S30P (p.Ser30Pro), gnomAD 6-154039632-T-C, REVEL 0.18, MetaLR 0.01
- W31* (p.Trp31Ter), NCI-TCGA Cosmic COSV5768, cosmic curated COSV57682, gnomAD rs1413027831, CADD 33.00, Variant assessed as somatic; high impact.
- W31R (p.Trp31Arg), TOPMed rs1423291779, gnomAD rs1423291779, REVEL 0.12, CADD 24.90
- W31G (p.Trp31Gly), gnomAD 6-154039632-TC-T, CADD 25.60
- V32I (p.Val32Ile), cosmic curated COSV10801
- V32L (p.Val32Leu), gnomAD rs1160067850, REVEL 0.06, CADD 16.30
- V32D (p.Val32Asp), gnomAD 6-154011013-T-A, CADD 2.75, SIFT 0.03
- V32V (p.Val32Val), gnomAD 6-154011014-C-A, CADD 5.57
- V32G (p.Val32Gly), rs768254051, gnomAD 6-154039180-T-G, CADD 15.80, SIFT 0.00
- V32F (p.Val32Phe), gnomAD 6-154039404-G-T, CADD 7.22, SIFT 0.00
- V32M (p.Val32Met), rs77114424, gnomAD 6-154039497-G-A, CADD 12.90, SIFT 0.14
- V32A (p.Val32Ala), gnomAD 6-154039639-T-C, REVEL 0.13, MetaLR 0.01
- N33S (p.Asn33Ser), gnomAD 6-154039642-A-G, REVEL 0.07, MetaLR 0.04
- N33N (p.Asn33Asn), rs1699772374, gnomAD 6-154039643-C-T, CADD 12.20
- N33K (p.Asn33Lys), gnomAD 6-154039643-C-G, REVEL 0.08, MetaLR 0.03
- L34F (p.Leu34Phe), gnomAD 6-154039248-C-T, CADD 9.78, SIFT 0.00
- p.Leu29 Gln31del, gnomAD 6-154039440-GAGCT, CADD 15.50
- L34V (p.Leu34Val), gnomAD 6-154039443-C-G, CADD 19.90, SIFT 0.19
- L34L (p.Leu34Leu), rs1583170716, gnomAD 6-154039443-C-T, CADD 8.31
- L34S (p.Leu34Ser), gnomAD 6-154039645-T-C, REVEL 0.17, MetaLR 0.01
- S35A (p.Ser35Ala), Ensembl rs2128394116
- S35F (p.Ser35Phe), ExAC rs768405841, TOPMed rs768405841, gnomAD rs768405841
- S35Y (p.Ser35Tyr), ExAC rs768405841, TOPMed rs768405841, gnomAD rs768405841, CADD 9.07, drug response, Tramadol response
- S35P (p.Ser35Pro), rs1295071766, gnomAD 6-154039257-T-C, CADD 12.20, SIFT 0.15
- S35S (p.Ser35Ser), rs201221097, gnomAD 6-154039259-C-T, CADD 0.88
- S35T (p.Ser35Thr), gnomAD 6-154039647-T-A, REVEL 0.17, MetaLR 0.01
- H36N (p.His36Asn), ExAC rs199953844, TOPMed rs199953844, gnomAD rs199953844, REVEL 0.11, CADD 19.90
Public OPRM1 analysis runs
- OPRM1 analysis run — OPRM1 (924 variants) — completed 2026-07-23