COMT Gene: Catechol-O-Methyltransferase
Key regulator of dopamine, epinephrine, and norepinephrine metabolism; implicated in neuropsychiatric disorders and pain sensitivity.
Gene Information Card
| Symbol | COMT |
|---|---|
| Full Name | Catechol-O-Methyltransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 22q11.21 |
| NCBI Gene ID | 1312 ncbi.nlm.nih.gov/gene/1312 |
| Ensembl ID | ENSG00000093010 |
| UniProt ID | P21964 |
| OMIM ID | 116790 |
| HGNC ID | 2228 |
| Aliases | COMT1, COMT2, HEL-S-98n |
Description
The COMT gene encodes catechol-O-methyltransferase, an enzyme that catalyzes the O-methylation and subsequent degradation of catecholamines including dopamine, epinephrine, and norepinephrine. It plays a critical role in neurotransmitter homeostasis in the central nervous system and peripheral tissues. Two major isoforms exist: soluble (S-COMT) and membrane-bound (MB-COMT). A common functional polymorphism, Val158Met (rs4680), affects enzyme activity and is associated with various neuropsychiatric conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Reduced COMT activity (Met158 allele) leads to increased prefrontal dopamine, altering cognitive function and psychosis risk. | OMIM #181500; multiple association studies |
| Parkinson disease | COMT inhibitors (e.g., entacapone) are used to prolong levodopa efficacy; genetic variants influence drug response. | ClinVar; NCBI GeneReviews |
| Panic disorder | Val158Met polymorphism associated with altered catecholamine metabolism and anxiety susceptibility. | OMIM #167870; case-control studies |
| Chronic pain (fibromyalgia) | Low-activity Met158 allele linked to higher pain sensitivity due to elevated synaptic catecholamines. | ClinVar; PMID: 15817855 |
| Breast cancer | COMT polymorphisms may modulate estrogen metabolism and risk; evidence inconclusive. | COSMIC; PMID: 12506202 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 32.5 | Medium |
| Prefrontal cortex | 18.2 | Medium |
| Adrenal gland | 15.8 | Medium |
| Kidney | 12.1 | Low |
| Whole blood | 1.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 28.4 | Hepatocellular carcinoma |
| SH-SY5Y (neuroblastoma) | 22.1 | Neuronal model |
| HEK293 (embryonic kidney) | 14.7 | Common overexpression system |
| MCF7 (breast) | 6.2 | Estrogen receptor positive |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs4680 (Val158Met) | Missense (G>A) | ~50% in Europeans | Reduces enzyme activity 3-4 fold; associated with psychiatric and pain phenotypes |
| rs6267 (Ala72Ser) | Missense (G>T) | <1% | Rare; decreased activity; possible schizophrenia risk |
| rs4818 (Leu136Leu) | Synonymous (C>G) | ~30% | May affect mRNA stability; linked to pain sensitivity |
| rs165599 (3' UTR) | SNP (A>G) | ~35% | Associated with altered COMT expression in brain |
Mutation functional classification
Loss of Function (LOF)
rs4680 (Met158) reduces enzymatic activity; rs6267 (Ala72Ser) also decreases activity.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in COMT.
Dominant Negative (DN)
Not described; COMT acts as a monomer and dominant-negative effects are not established.
View complete mutation data：
Gene Ontology (GO)
| • catechol O-methyltransferase activity (GO:0004098) | • catecholamine metabolic process (GO:0006584) |
| • cytoplasm (GO:0005737) | • cytosol (GO:0005829) |
| • membrane (GO:0016020) | • dopamine catabolic process (GO:0042420) |
| • norepinephrine catabolic process (GO:0042423) | • epinephrine catabolic process (GO:0042425) |
Pathways
• Catecholamine metabolism (Reactome: R-HSA-379401)
• Dopamine degradation (KEGG: hsa00350)
• Tyrosine metabolism (KEGG: hsa00350)
• Neurotransmitter clearance (GO:0001504)
Protein Summary
Catechol-O-methyltransferase (COMT) is a 271-amino-acid (MB-COMT) or 221-amino-acid (S-COMT) enzyme that transfers a methyl group from S-adenosyl-L-methionine to catechol substrates. It is essential for the inactivation of catecholamine neurotransmitters and catechol drugs. The enzyme is expressed in liver, kidney, brain, and blood cells. The Val158Met polymorphism (rs4680) is the most studied functional variant, with the Met allele associated with lower thermostability and reduced activity. COMT inhibitors are used clinically in Parkinson disease to enhance levodopa bioavailability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COMT Knockout HEK293 Cell Line | EDJ-KQ2043 | Human | 1312 | Details Get a Quote |
| COMT Knockout A-549 Cell Line | EDJ-KQ22089 | Human | 1312 | Details Get a Quote |
| COMT Knockout HCT 116 Cell Line | EDJ-KQ22090 | Human | 1312 | Details Get a Quote |
| COMT Knockout HeLa Cell Line | EDJ-KQ22091 | Human | 1312 | Details Get a Quote |
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