Annotated PGx Gene Information for COMT
Submitted by: Amy E. Hodge (PharmGKB)
Reviewed by: Under Review
Submitted date: August 31, 2006
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| Gene HGNC Name: | COMT |
|---|---|
| Introductory Information: | The COMT gene encodes for the catechol-O-methyltransferase, an AdoMet- and Mg2+-dependent methyltransferase whose substrates are catechols, including neurotransmitters like norepinephrine and catecholestrogens. The COMT protein exists in a membrane-bound form as well as a soluble form that are produced from alternative promoters on one chromosome 22 gene. COMT has been resequenced using DNA samples from AA and CA subjects [see COMT]. The membrane-bound form contains an extra 50 amino acids at the N-terminus. The difference in activity between the two forms is a function of altered protein levels and is not the result of intrinsic differences in the specific activities. COMT is able to metabolize the drugs levodopa and methyldopa. The most well-studied polymorphism in COMT, COMT:Val108Met (COMT:Val158Met), has been linked to psychiatric disorders, particularly schizophrenia, opioid receptor-mediated pain perception, and breast cancer (see Variant Page for more details). The association of COMT polymorphisms with neuropsychiatric diseases is thought to be related to the metabolism of catecholamine neurotransmitters, while the role of COMT in breast cancer is thought to result from the methylation of catecholestrogens [PMID: 8725388, 16421368]. Several haplotype analyses on COMT with regard to schizophrenia have been published [PMID: 15645182, 12402217, 15098000, 15124004]. |
| Key PubMed IDs: | 16807786, 15305167, 15645182, 12402217, 15098000, 15124004, 8725388, 16421368, 14966473 |
| Key Pathways: | Antiestrogen Pathway (Estrogen metabolism) |
| Drugs/Substrates: | Substrates: catechols, including neurotransmitters like catecholestrogens and norepinephrine Drugs: levodopa, methyldopa |
| Phenotypes/Diseases: | Diseases: Schizophrenia, Breast Neoplasms, Pain |
| Important Variants: | COMT:Val108Met (COMT:Val158Met) |