OPRM1

Chr 6

opioid receptor mu 1

Also known as: LMOR, M-OR-1, MOP, MOR, MOR1, OPRM

The mu opioid receptor encoded by this gene serves as the principal target for endogenous opioid peptides like beta-endorphin and enkephalins, as well as synthetic opioids including morphine and fentanyl, functioning as a G-protein-coupled receptor that regulates pain sensitivity, reward pathways, and drug dependence. Mutations in OPRM1 are associated with variations in opioid and alcohol addiction susceptibility and altered pain sensitivity, though the causal relationship remains unclear. This gene is not highly constrained against loss-of-function mutations (pLI near zero), and inheritance patterns for addiction susceptibility variants appear to follow typical Mendelian patterns.

GeneReviewsResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.31
Clinical SummaryOPRM1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 87 VUS of 139 total submissions
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Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — OPRM1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.31LOEUF
pLI 0.000
Z-score 0.53
OE 0.87 (0.591.31)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.62Z-score
OE missense 1.10 (1.001.21)
311 obs / 281.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.87 (0.591.31)
00.351.4
Missense OE1.10 (1.001.21)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 17 / 19.5Missense obs/exp: 311 / 281.8Syn Z: -0.49
DN
0.7229th %ile
GOF
0.77top 25%
LOF
0.3550th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

139 submitted variants in ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic3
VUS87
Likely Benign12
Benign5
24
Pathogenic
3
Likely Pathogenic
87
VUS
12
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
3
0
3
VUS
0
83
4
0
87
Likely Benign
0
8
0
4
12
Benign
1
2
1
1
5
Total193325131

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

OPRM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Opioid Use DisorderPregnancy Related

Predicting and Preventing Adverse Maternal and Child Outcomes of Opioid Use Disorder in Pregnancy

RECRUITING
NCT05942313Ilana HullStarted 2023-08-28
Buprenorphine/ Methadone exposure
Parkinson DiseaseImpulse Control Disorder

Efficacy of a Prediction Model-based Algorithm to PREVENT Drug-induced Impulse Control Disorders in Parkinson's Disease

NOT YET RECRUITING
NCT07505394Phase NAAssistance Publique - Hôpitaux de ParisStarted 2026-06-01
Algorithm-guided groupStandard of Care (SoC) group
Fibromyalgia (FM)tDCSDuloxetine

Home-based Transcranial Direct Current Stimulation (tDCS) Compared to Duloxetine: Non-inferiority Clinical Trial (FIBROSTIM)

RECRUITING
NCT07203339Phase NAHospital de Clinicas de Porto AlegreStarted 2025-09-30
Transcranial direct current stimulation (tDCS) plus placebo.Duloxetine (60 mg) once dailyHome-based transcranial direct current stimulation
PPAPSpine Fusion

Personalized Perioperative Analgesia Platform (PPAP) for Pediatric Spine Fusion Surgery (sIRB)

RECRUITING
NCT05367609Phase NASenthil SadhasivamStarted 2022-09-20
Preoperative Genotyping
Paraphilic DisordersSexual AddictionParasomnia

Paraphilic Disorders and Other Conditions With Risk for Sexual Violence: a Case-control Study

RECRUITING
NCT05861752Region StockholmStarted 2022-10-19
Treatment as usual
Stage I Breast Cancer AJCC v7Stage IA Breast Cancer AJCC v7Stage IB Breast Cancer AJCC v7

Electroacupuncture Therapy in Reducing Chronic Pain in Patients After Breast Cancer Treatment

ACTIVE NOT RECRUITING
NCT02754752Phase PHASE2M.D. Anderson Cancer CenterStarted 2016-09-13
Electroacupuncture TherapyElectroacupuncture TherapyLaboratory Biomarker Analysis
PregnancyPostpartumChildbirth

HIIT vs MICT During Pregnancy and Health and Birth Outcomes in Mothers and Children

RECRUITING
NCT05009433Phase NAGdansk University of Physical Education and SportStarted 2021-06-24
High intensity interval training program for pregnant womenModerate intensity continuous training program for pregnant womenStandard obstetric care with extended education on healthy lifestyle
AnalgesiaCardiac Surgery

Precision Analgesia for Cardiac Surgery

NOT YET RECRUITING
NCT05612399Kathirvel SubramaniamStarted 2026-05
Clinical Literature
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