COMT

Chr 22

catechol-O-methyltransferase

Also known as: HEL-S-98n

Catechol-O-methyltransferase catalyzes the transfer of a methyl group from S-adenosylmethionine to catecholamines, including the neurotransmitters dopamine, epinephrine, and norepinephrine. This O-methylation results in one of the major degradative pathways of the catecholamine transmitters. In addition to its role in the metabolism of endogenous substances, COMT is important in the metabolism of catechol drugs used in the treatment of hypertension, asthma, and Parkinson disease. COMT is found in two forms in tissues, a soluble form (S-COMT) and a membrane-bound form (MB-COMT). The differences between S-COMT and MB-COMT reside within the N-termini. Several transcript variants are formed through the use of alternative translation initiation sites and promoters. [provided by RefSeq, Sep 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSchizophrenia
12
Active trials
377
Pubs (1 yr)
P/LP submissions
P/LP missense
1.70
LOEUF
GOF
Mechanism· predicted
📖
GeneReview available — COMT
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?
1.70LOEUF
pLI 0.000
Z-score -0.04
OE 1.02 (0.611.70)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.43Z-score
OE missense 0.91 (0.801.04)
157 obs / 172.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?1.02 (0.611.70)
00.351.4
Missense OE?0.91 (0.801.04)
00.61.4
Synonymous OE?0.94
01.21.6
LoF obs/exp: 9 / 8.9Missense obs/exp: 157 / 172.9Syn Z: 0.45

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

COMT · 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

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
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
Healthy

Effect of Sleep Extension in Prevention to Sleep Deprivation

RECRUITING
NCT06928168Phase NACentre Hospitalier Universitaire de Saint EtienneStarted 2025-06-12
Total sleep deprivationpartial sleep deprivationReproductibility
Vasovagal Syncope

Study of Atomoxetine in the Prevention of Vasovagal Syncope

RECRUITING
NCT05159687Phase PHASE3University of CalgaryStarted 2022-06-01
Atomoxetine HydrochloridePlacebo
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
CannabisTHC

Modulation of THC Effects by CBD: a Dose-ranging Study

RECRUITING
NCT06099379Phase PHASE1, PHASE2Centre hospitalier de l'Université de Montréal (CHUM)Started 2024-06-27
∆9-tetrahydrocannabinol
Mild Cognitive Impairment

REACT MCI - Repeated Advanced Cognitive Training in Mild Cognitive Impairment

ACTIVE NOT RECRUITING
NCT04792528Phase NASorlandet Hospital HFStarted 2021-05-15
Computerized cognitive training.Generalized brain training / Active control
Breast CancerChronic PainAcute Pain

Evaluation And Risk Assessment For Persistent Postsurgical Pain After Breast Surgery

ACTIVE NOT RECRUITING
NCT03408717KK Women's and Children's HospitalStarted 2018-01-03
QuestionnairesMechanical Temporal Summation assessmentPain threshold assessment
Patients With Schizophrenia

PhaRmacOgenetics and Therapeutic Drug Monitoring In SchizophrEnia

NOT YET RECRUITING
NCT05839613Phase NAAssistance Publique Hopitaux De MarseilleStarted 2023-05
Therapeutic Drug Monitoring (TDM) and Pharmacogenetics (PG)
PPAPSpine Fusion

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

RECRUITING
NCT05367609Phase NASenthil SadhasivamStarted 2022-09-20
Preoperative Genotyping
Hyperhomocysteinemia

Evaluation of a Genetically Determined Personalized Approach in Prescribing Biologically Active Substances in Patients With Elevated Blood Homocysteine Levels.

RECRUITING
NCT06264570Phase NAS.LAB (SOLOWAYS)Started 2023-10-23
B-TMG supplementationB-SAM supplementationB-TMG placebo
Sleep ApneaSleep-Disordered Breathing

The Meaning of Dopaminergic Pathway in Sleep Breathing Disorders.

ENROLLING BY INVITATION
NCT05890911Wroclaw Medical UniversityStarted 2023-06-01
PolysomnographyBlood dopamine level measurementGenetical test