COMT
Catechol-O-methyltransferase
Gene Number: 1312
Location: 22q11.21
Key Functions: Dopamine metabolism, catecholamine degradation, cognitive control, pain modulation, stress resilience, and emotional regulation
The COMT gene produces catechol-O-methyltransferase, an enzyme that helps break down chemical messengers including dopamine and norepinephrine. It is particularly important in the prefrontal cortex, a brain region involved in attention, planning, and working memory. [R].
The best-studied COMT variant is rs4680, also called Val158Met. The G allele encodes valine (Val), while the A allele encodes methionine (Met). The Met form is less stable and has lower enzyme activity. This is the basis of the commonly used descriptions “slow COMT” and “fast COMT.” These describe relative enzyme activity [R].
Explore your available results below. For another part of the biology of learning and memory, visit our BDNF gene guide.
SNP ID | Your Genotype | Alt Allele | Interpretation |
|---|---|---|---|
rs4680 | Analyze your DNA to see your genotype | A | Analyze your DNA to see a personalized result. |
rs4633 | Analyze your DNA to see your genotype | T | Analyze your DNA to see a personalized result. |
rs4680 — COMT Val158Met
AA – Met/Met genotype reduces COMT activity by ~4×; linked to higher dopamine levels and greater stress sensitivity (R, R).
AG – Intermediate COMT activity; balanced dopamine clearance (R, R).
GG – Val/Val genotype increases COMT activity; lower dopamine levels; may improve stress resilience (R).
Functional effect: The A (Met) allele leads to reduced enzyme activity, resulting in higher synaptic dopamine, which can enhance cognitive function but also heighten stress vulnerability.
rs4633 — a synonymous COMT variant
TT – Greatest reduction in COMT mRNA; lower enzyme levels and significantly slower dopamine breakdown (R).
TC – Slight reduction in mRNA expression; moderate effect on dopamine clearance (R).
CC – Likely normal COMT mRNA expression (R).
Functional effect: This synonymous variant influences mRNA stability, with T alleles leading to lower COMT levels and altered dopamine metabolism.
Putting the results in context
COMT results describe genetic variation, rather than measuring current brain chemistry. Read our brain chemistry reports overview for broader context, or see how we build DNA reports to understand how research informs our interpretations.
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