COMT
Chr 22catechol-O-methyltransferase
Also known as: HEL-S-98n
Catechol-O-methyltransferase catalyzes the O-methylation and inactivation of catecholamine neurotransmitters including dopamine, epinephrine, and norepinephrine, representing a major degradative pathway for these transmitters. This gene is highly tolerant to loss-of-function variants and is primarily associated with variation in catechol-O-methyltransferase activity rather than Mendelian disease. The enzyme also metabolizes catechol-based medications used to treat hypertension, asthma, and Parkinson disease.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is gain-of-function.
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
81 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 59 | 0 | 59 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 1 | 6 | 8 | 0 | 15 |
Likely Benign | 0 | 0 | 2 | 2 | 4 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 1 | 6 | 72 | 2 | 81 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
The Meaning of Dopaminergic Pathway in Sleep Breathing Disorders.
ENROLLING BY INVITATIONPredicting and Preventing Adverse Maternal and Child Outcomes of Opioid Use Disorder in Pregnancy
RECRUITINGEfficacy of a Prediction Model-based Algorithm to PREVENT Drug-induced Impulse Control Disorders in Parkinson's Disease
NOT YET RECRUITINGEffect of Sleep Extension in Prevention to Sleep Deprivation
RECRUITINGHome-based Transcranial Direct Current Stimulation (tDCS) Compared to Duloxetine: Non-inferiority Clinical Trial (FIBROSTIM)
RECRUITINGPersonalized Perioperative Analgesia Platform (PPAP) for Pediatric Spine Fusion Surgery (sIRB)
RECRUITINGModulation of THC Effects by CBD: a Dose-ranging Study
RECRUITINGPhaRmacOgenetics and Therapeutic Drug Monitoring In SchizophrEnia
NOT YET RECRUITINGElectroacupuncture Therapy in Reducing Chronic Pain in Patients After Breast Cancer Treatment
ACTIVE NOT RECRUITINGEvaluation And Risk Assessment For Persistent Postsurgical Pain After Breast Surgery
ACTIVE NOT RECRUITINGStudy of Atomoxetine in the Prevention of Vasovagal Syncope
RECRUITINGEvaluation of a Genetically Determined Personalized Approach in Prescribing Biologically Active Substances in Patients With Elevated Blood Homocysteine Levels.
RECRUITINGExternal Resources
Links to major genomics databases and tools