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Symbol COMT contributors: mct/npt/pgu - updated : 05-04-2013
HGNC name catechol-O-methyltransferase
HGNC id 2228
TYPE functioning gene
STRUCTURE 28.24 kb     6 Exon(s)
10 Kb 5' upstream gene genomic sequence study
text structure a CAG repeat
MAPPING cloned Y linked N status confirmed
Physical map
LOC391295 22 similar to serine/threonine kinase FKSG81; spermiogenesis associated 4 STK22B 22q11.2 serine/threonine kinase 22B (spermiogenesis associated) DGCR14 22q11.21 DiGeorge syndrome critical region gene 14 GSCL 22q11.21 goosecoid-like SLC25A1 22q11.21 solute carrier family 25 (mitochondrial carrier; citrate transporter), member 1 CLTCL1 22q11.21 clathrin, heavy polypeptide-like 1 HIRA 22q11.21-q11.23 HIR histone cell cycle regulation defective homolog A (S. cerevisiae) MRPL40 22q11.2 mitochondrial ribosomal protein L40 LOC128977 22q11.21 hypothetical protein LOC128977 UFD1L 22q11.21 ubiquitin fusion degradation 1-like CDC45L 22q11.2 CDC45 cell division cycle 45-like (S. cerevisiae) CLDN5 22q11.21 claudin 5 (transmembrane protein deleted in velocardiofacial syndrome) PNUTL1 22q11.21 peanut-like 1 (Drosophila) GP1BB 22q11.21 glycoprotein Ib (platelet), beta polypeptide LOC391296 22 similar to contains similarity to cell wall-plasma membrane linker protein~gene_id:MKA23.5 TBX1 22q11.21 T-box 1 GNB1L 22q11.2 guanine nucleotide binding protein (G protein), beta polypeptide 1-like FLJ21125 22q11.21 hypothetical protein FLJ21125 TXNRD2 22q11.21 thioredoxin reductase 2 COMT 22q11.2 catechol-O-methyltransferase ARVCF 22q11.21 armadillo repeat gene deletes in velocardiofacial syndrome DKFZp761P1121 22q11.21 hypothetical protein DKFZp761P1121 DGCR8 22q11.2 DiGeorge syndrome critical region gene 8 HTF9C 22q11.2 DiGeorge syndrome critical region gene 8 RANBP1 22q11.21 RAN binding protein 1 ZDHHC8 22q11.1 zinc finger, DHHC domain containing 8 LOC388849 22 LOC388849 FLJ32575 22q11.21 hypothetical protein FLJ32575 RTN4R 22q11.21 reticulon 4 receptor LOC388850 22 similar to proline dehydrogenase (oxidase) 1; proline oxidase 2; p53 induced protein; tumor protein p53 inducible protein 6 DGCR6L 22q11.2 DiGeorge syndrome critical region gene 6-like LOC391297 22 LOC391297 LOC284859 22q11.21 hypothetical gene supported by BC039313 GGT2 22q11 gamma-glutamyltransferase 2 LOC284874 22q11.21 hypothetical LOC284874 LOC388851 22 similar to phosphatidylinositol 4-kinase, catalytic, alpha polypeptide isoform 2; phosphatidylinositol 4-kinase, type II, alpha; phosphatidylinositol 4-kinase, type III, alpha; phosphatidylinositol 4-kinase 230 LOC388852 22 similar to hypothetical protein LOC388853 22 similar to Sushi domain (SCR repeat) containing LOC391298 22 similar to KIAA0649 gene product LOC388854 22 similar to Gamma-glutamyltranspeptidase 1 precursor (Gamma-glutamyltransferase 1) (CD224 antigen) LOC388855 22 hypothetical gene supported by BC039313 LOC388856 22 hypothetical gene supported by BC039313 LOC388857 22 similar to KIAA0649 gene product LOC391299 22 similar to Collagen alpha 1(II) chain precursor USP41 22q11.22 ubiquitin specific protease 41 ZNF74 22q11.21 zinc finger protein 74 (Cos52) SCARF2 22q11.21 scavenger receptor class F, member 2 FLJ14360 22q11.21 hypothetical protein FLJ14360
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 initiation site 2262 30 271 - 2011 21846718
long 5'utr
4 initiation site 2035 - 221 - 2011 21846718
  • variant 4 - S-COMT, soluble
  • short 5'utr downstream initiation site
  • subcellular localization: intracellular, cytoplasm, cytosol, microsome
  • 6 - 2304 - 271 membrane-bound (MB), main form in the brain 2011 21846718
  • variant 1, MB-COMT
  • can inactivate synaptic and extrasynaptic dopamine on the surface of presynaptic and postsynaptic neurons
  • 6 - 2279 30 271 - 2011 21846718
    Type widely
       expressed in (based on citations)
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
    physiological period embryo, pregnancy
    Text placenta, marginal zone and cortical plate
  • mammalian catechol-O-methyltransferase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • degrading the catecholamine and inactivating catechol drugs in the central nervous system
  • important modulator in the catabolism of extraneural dopamine, which plays an important role in drug reward mechanisms
  • having a major function in regulating epinephrine, norepinephrine, and dopamine levels in the brain, particularly in the prefrontal cortex
  • regulating dopamine levels in the brain
  • plays a particular role in modulating dopamine in prefrontal cortex
  • may have a general homeostatic role in regulating several genes, such as SLC6A3, to enhance dopaminergic signaling
  • key enzyme for inactivation and metabolism of catechols, including dopamine, norepinephrine, caffeine, and estrogens
  • dominates the regulation of dopamine metabolism in the prefrontal cortex
  • COMT effects are particularly evident in prefrontal cortex-dependent cognitive functions including executive control, working memory, attentional control and long-term memory
  • contributes to modultion the perception of pain, via non-competitive binding to the site bound by catechol substrates with a binding affinity comparable to the binding affinity of catechol itself
  • role of APOE and COMT genes in prospective and retrospective memory traits
  • one of the most important enzymes involved in estrogen metabolism
    metabolism aminoacid , drug
    signaling neurotransmission
    tyrosine, catechol drugs
    a component
    small molecule
  • regulating SLC6A3
  • interaction of BDNF by COMT on human cortical plasticity
  • cell & other
    inhibited by serotonin
    corresponding disease(s) SCZD4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    hemizygous deletion in 22q11 microdeletion syndromes (velocardiofacial syndrome [VCFS] or DiGeorge syndrome [DGS])
  • potential risk factor for homicidal behavior in schizophrenia
  • to schizophrenia in a French series and bipolar disorders
  • to obesity
  • to cisplatin-induced hearing loss in children
  • Variant & Polymorphism SNP , other
  • Val158Met involved in risk for schizophrenia and bipolar disorders
  • The COMT Ex4-76C > G (L136L) polymorphism appears to play a role in large increases in BMI
  • variant rs9332377, associated to cisplatin-induced hearing loss in children
  • val158met polymorphism in the COMT gene contributes significantly to inter-individual differences in neural pain processing: in healthy people
  • Candidate gene
    Therapy target
    inhibition of COMT via serotonin binding contributes to pain hypersensitivity, providing additional strategies for the treatment of clinical pain conditions
    promising target for modulation of cognitive functions and dysfunctions
  • pregnant mice deficient in catechol-O-methyltransferase (COMT) show a pre-eclampsia-like phenotype resulting from an absence of 2-methoxyoestradiol (2-ME), a natural metabolite of oestradiol that is elevated during the third trimester of normal human pregnancy