rs769224

badMag 3.5

This is a synonymous variant in the COMT gene — it does not change the protein's amino acid sequence.

Key Literature Trait Associations

COMT Enzyme Activity

The COMT P199P variant (rs769224) is a rare synonymous SNP that forms part of the COMT haplotype block. The A allele is uncommon (~5% globally) and contributes to a haplotype associated with altered COMT enzyme activity, though its independent functional impact is minimal.

Diatchenko L et al. “Genetic basis for individual variations in pain perception and the development of a chronic pain condition.” Human Molecular Genetics (2005)

Allele A

OR —

p 4.0e-4

Candidate gene study

European

Kreyenbuhl J et al. “Long-term combination antipsychotic treatment in VA patients with schizophrenia.” Schizophrenia Research 84(1):90-99 (2006)

Allele A

OR —

p 2.0e-2

Candidate gene study

Nackley AG et al. “Low enzymatic activity haplotypes of the human catechol-O-methyltransferase gene: enrichment for marker SNPs.” Plos One (2009)

Allele A

OR —

p —

Candidate gene study

multi-ancestry

Diatchenko L et al. “Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli.” Pain (2006)

Allele A

OR —

p —

Candidate gene study

European

Antidepressant drug response

A haplotype spanning rs4633, rs4818, and rs769224 in the COMT gene was significantly associated with antidepressant response in a cohort of 308 Chinese Han patients with major depressive disorder, specifically in the non-SSRI treatment subgroup. Patients carrying certain COMT haplotypes tagged by rs769224 showed differential remission rates, though the study did not report specific odds ratios. The association is haplotype-level and has not been replicated in larger independent cohorts; it should be interpreted as preliminary evidence.

Xu Z et al. “Influence and interaction of genetic polymorphisms in catecholamine neurotransmitter systems and early life stress on antidepressant drug response.” Journal of Affective Disorders (2011)

Allele A

OR —

p —

N 308

Candidate gene study

East Asian

Autism spectrum disorder

A family-based association study in 151 Korean autism spectrum disorder trios found that a COMT haplotype including rs6269, rs4818, rs4680, and rs769224 showed significant over-transmission (haplotype p=0.004, FDR-corrected p=0.040). The dominant model also reached significance (p=0.009, FDR p=0.045). The association is limited to an East Asian population sample, is haplotype-level rather than SNP-specific, and requires replication in larger and more diverse cohorts.

Yoo HJ et al. “Association of the catechol-o-methyltransferase gene polymorphisms with Korean autism spectrum disorders.” Journal of Korean Medical Science (2013)

Allele A

OR —

p 4.0e-3

N 151

Candidate gene study

East Asian

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ClinVar annotation

Drug Response★★★☆

3 submitters1 publication

Tramadol response

View on ClinVar →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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