OPRM1

Chr 6

opioid receptor mu 1

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

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. [provided by RefSeq, Oct 2013]

GeneReviewsResearchGenerating clinical summary…
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
83 VUS of 108 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 OE?0.87 (0.591.31)
00.351.4
Missense OE?1.10 (1.001.21)
00.61.4
Synonymous OE?1.06
01.21.6
LoF obs/exp: 17 / 19.5Missense obs/exp: 311 / 281.8Syn Z: -0.49

This gene — mechanism propensity

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

108 submitted variants in ClinVar

Classification Summary

VUS83
Likely Benign12
Benign5
83
VUS
12
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
83
0
0
83
Likely Benign
0
8
0
4
12
Benign
1
2
1
1
5
Total19315100

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap OPRM1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

OPRM1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

PPAPSpine Fusion

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

RECRUITING
NCT05367609Phase NASenthil SadhasivamStarted 2022-09-20
Preoperative Genotyping
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
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
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
AnalgesiaCardiac Surgery

Precision Analgesia for Cardiac Surgery

NOT YET RECRUITING
NCT05612399Kathirvel SubramaniamStarted 2026-05
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
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
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 2026-07-01
Algorithm-guided groupStandard of Care (SoC) group