COMT
Chr 22catechol-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]
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene — mechanism propensity
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
85 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 | 1 | 0 | 0 | 0 | 1 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 1 | 30 | 9 | 0 | 40 |
Likely Benign | 0 | 1 | 7 | 17 | 25 |
Benign | 0 | 2 | 7 | 8 | 17 |
| Total | 2 | 33 | 23 | 25 | 83 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →393 pathogenic / likely-pathogenic (of 412) ClinVar copy-number / structural variants overlap COMT — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
COMT · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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 INVITATIONPhaRmacOgenetics and Therapeutic Drug Monitoring In SchizophrEnia
NOT YET RECRUITINGPersonalized Perioperative Analgesia Platform (PPAP) for Pediatric Spine Fusion Surgery (sIRB)
RECRUITINGEvaluation And Risk Assessment For Persistent Postsurgical Pain After Breast Surgery
ACTIVE NOT RECRUITINGEffect of Sleep Extension in Prevention to Sleep Deprivation
RECRUITINGElectroacupuncture Therapy in Reducing Chronic Pain in Patients After Breast Cancer Treatment
ACTIVE NOT RECRUITINGREACT MCI - Repeated Advanced Cognitive Training in Mild Cognitive Impairment
ACTIVE NOT RECRUITINGHome-based Transcranial Direct Current Stimulation (tDCS) Compared to Duloxetine: Non-inferiority Clinical Trial (FIBROSTIM)
RECRUITINGStudy of Atomoxetine in the Prevention of Vasovagal Syncope
RECRUITINGPrecision Analgesia for Cardiac Surgery
NOT YET RECRUITINGPredicting and Preventing Adverse Maternal and Child Outcomes of Opioid Use Disorder in Pregnancy
RECRUITINGModulation of THC Effects by CBD: a Dose-ranging Study
RECRUITINGExternal Resources
Links to major genomics databases and tools