rs4680 COMT
COMT Val158Met Met/Met. Lower COMT activity; higher dopamine levels. Associated with increased pain sensitivity, better memory, but higher stress vulnerability.
What is rs4680?
rs4680 is a single-nucleotide polymorphism (SNP) in the COMT gene (Catechol-O-methyltransferase). Each person carries two copies, one from each parent, so a result is reported as a pair of letters such as AA. The table below describes what studies associate with each genotype; the association is statistical, across populations, and is not a diagnosis.
What does each rs4680 genotype mean?
| Genotype | Association | What the evidence says | Confidence |
|---|---|---|---|
| AA | typical / lower | COMT Val158Met Met/Met. Lower COMT activity; higher dopamine levels. Associated with increased pain sensitivity, better memory, but higher stress vulnerability. | 82% |
| GA / AG | typical / lower | COMT Val/Met heterozygous. Intermediate dopamine metabolism. | 78% |
| GG | typical / lower | COMT Val/Val. Higher COMT activity; lower dopamine. Better stress resilience but may have lower pain threshold. | 82% |
How common is the A allele of rs4680?
Minor-allele frequency by population (gnomAD / 1000 Genomes):
| European | 50.0% |
|---|---|
| East Asian | 28.0% |
| African | 40.0% |
| South Asian | 42.0% |
| Admixed American | 45.0% |
| Global | 42.0% |
Which drugs have annotations for rs4680?
PharmGKB clinical annotations (level 1A is the strongest evidence, 4 the weakest):
| Drug | Annotation type | Evidence level |
|---|---|---|
| antipsychotics | Toxicity, Other, Efficacy, Dosage, Metabolism/PK | 3 |
| fluvoxamine | Toxicity, Other, Efficacy, Dosage, Metabolism/PK | 3 |
Is rs4680 on 23andMe and AncestryDNA chips?
Yes — it is genotyped directly on 23andMe V3, 23andMe V4, 23andMe V5, AncestryDNA V1, AncestryDNA V2. Orviva reads it from a raw-data export without imputation.
Sources
Upload your 23andMe, AncestryDNA or WeGene raw file → · Ask G2: “What is my genotype at rs4680 and what does it mean for me?”
Genetic associations describe risk across populations, not a diagnosis for any one person. Most variants shift risk modestly and act alongside lifestyle, environment and other genes. Consumer DNA chips do not read every position and can be wrong at any single one. For general education only; talk to a clinician or genetic counsellor before acting on anything here, and never change a prescribed medicine without your prescriber.