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COMT Gene

protein-coding   GIFtS: 76
GCID: GC22P019929

Catechol-O-Methyltransferase

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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
catechol-O-methyltransferase1 2
EC 2.1.1.63 8
HEL-S-98n2
Catechol O-Methyltransferase2
Epididymis Secretory Sperm Binding Protein Li 98n2

External Ids:    HGNC: 22281   Entrez Gene: 13122   Ensembl: ENSG000000930107   OMIM: 1167905   UniProtKB: P219643   

Export aliases for COMT gene to outside databases

Previous GC identifers: GC22P016869 GC22P018303 GC22P003549


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for COMT Gene:
Catechol-O-methyltransferase catalyzes the transfer of a methyl group from S-adenosylmethionine to catecholamines,
including the neurotransmitters dopamine, epinephrine, and norepinephrine. This O-methylation results in one of
the major degradative pathways of the catecholamine transmitters. In addition to its role in the metabolism of
endogenous substances, COMT is important in the metabolism of catechol drugs used in the treatment of
hypertension, asthma, and Parkinson disease. COMT is found in two forms in tissues, a soluble form (S-COMT) and a
membrane-bound form (MB-COMT). The differences between S-COMT and MB-COMT reside within the N-termini. Several
transcript variants are formed through the use of alternative translation initiation sites and promoters.
(provided by RefSeq, Sep 2008)

GeneCards Summary for COMT Gene:
COMT (catechol-O-methyltransferase) is a protein-coding gene. Diseases associated with COMT include panic disorder, and neurotic disorder. GO annotations related to this gene include magnesium ion binding and catechol O-methyltransferase activity. An important paralog of this gene is LRTOMT.

UniProtKB/Swiss-Prot: COMT_HUMAN, P21964
Function: Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and
catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA,
alpha-methyl DOPA and isoproterenol

summary for COMT Gene:
Catechol-O-methyltransferase (COMT) is involved in metabolism of catecholamines (dopamine, adrenalin and
noradrenalin). COMT is localized to postsynaptic neurons where it degrades neurotransmitters following their
release.

Gene Wiki entry for COMT (Catechol-O-methyl transferase) Gene

PharmGKB "VIP" summary for COMT


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000022.11  NT_011520.13  NC_018933.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the COMT gene promoter:
         GR   PPAR-alpha   PPAR-gamma1   PPAR-gamma2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 3): COMT promoter sequence
   Search Chromatin IP Primers for COMT

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat COMT


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 22q11.21   Ensembl cytogenetic band:  22q11.21   HGNC cytogenetic band: 22q11.21

COMT Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
COMT gene location

GeneLoc information about chromosome 22         GeneLoc Exon Structure

GeneLoc location for GC22P019929:  view genomic region     (about GC identifiers)

Start:
19,929,130 bp from pter      End:
19,957,498 bp from pter
Size:
28,369 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: COMT_HUMAN, P21964 (See protein sequence)
Recommended Name: Catechol O-methyltransferase  
Size: 271 amino acids; 30037 Da
Cofactor: Binds 1 magnesium ion per subunit
Mass spectrometry: Mass=24352; Mass_error=2; Method=Electrospray; Range=52-271; Source=PubMed:8020475;
3 PDB 3D structures from and Proteopedia for COMT:
3A7E (3D)        3BWM (3D)        3BWY (3D)    
Secondary accessions: A8MPV9 Q6IB07 Q6ICE6
Alternative initiation: 2 isoforms:  P21964-1   P21964-2   

Explore the universe of human proteins at neXtProt for COMT: NX_P21964

Explore proteomics data for COMT at MOPED

Post-translational modifications: 

  • The N-terminus is blocked1
  • Ubiquitination2 at Lys179, Lys212, Lys259
  • Modification sites at PhosphoSitePlus
  • 3 DME Specific Peptides for COMT (P21964)
     GTVLLADNVI  LLLEECGLLR  LELGAYCGYSAVRMARLL 


    See COMT Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (4 alternative transcripts): 
    NP_000745.1  NP_001128633.1  NP_001128634.1  NP_009294.1  

    ENSEMBL proteins: 
     ENSP00000354511   ENSP00000383966   ENSP00000385917   ENSP00000384654   ENSP00000403958  
     ENSP00000207636   ENSP00000385150   ENSP00000387695   ENSP00000416778  
    Reactome Protein details: P21964

    COMT Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    R&D Systems Recombinant & Natural Proteins for COMT
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein for COMT
    OriGene Protein Over-expression Lysate for COMT
    OriGene MassSpec for COMT
    OriGene Custom Protein Services for COMT
    GenScript Custom Purified and Recombinant Proteins Services for COMT
    Novus Biologicals COMT Proteins
    Novus Biologicals COMT Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    ProSpec Recombinant Protein for COMT
    Cloud-Clone Corp. Proteins for COMT

    COMT Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of COMT
    R&D Systems Antibodies for COMT
    OriGene Antibodies for COMT
    OriGene Custom Antibody Services for COMT
    Novus Biologicals COMT Antibodies
    Abcam antibodies for COMT
    Cloud-Clone Corp. Antibodies for COMT
    ThermoFisher Antibody for COMT
    LSBio Antibodies in human, mouse, rat for COMT

    COMT Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for COMT
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for COMT
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for COMT
    Cloud-Clone Corp. CLIAs for COMT


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    3 InterPro protein domains:
     IPR017128 Catechol_O-MeTrfase_euk
     IPR025782 Catechol_O-MeTrfase
     IPR002935 O-MeTrfase_3

    Graphical View of Domain Structure for InterPro Entry P21964

    ProtoNet protein and cluster: P21964

    1 Blocks protein domain: IPB002935 O-methyltransferase

    UniProtKB/Swiss-Prot: COMT_HUMAN, P21964
    Similarity: Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-dependent
    O-methyltransferase family


    COMT for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: COMT_HUMAN, P21964
    Function: Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and
    catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA,
    alpha-methyl DOPA and isoproterenol
    Catalytic activity: S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol

         Genatlas biochemistry entry for COMT:
    catechol-O-methyltransferase,with CAG repeat,degrading the catecholamine and inactivating catechol drugs in the
    central nervous system,putative minor contributor to schizophrenia susceptibility in a French series,but
    potential risk factor for homicidal behavior in schizophrenia and potential risk factor of high activity Val
    allele in attention deficit hyperactivity disorder

         Enzyme Number (IUBMB): EC 2.1.1.61 2

         Gene Ontology (GO): 3 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000287magnesium ion binding IEA--
    GO:0008171O-methyltransferase activity TAS1707278
    GO:0016206catechol O-methyltransferase activity IEA--
         
    COMT for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for COMT:
     Increased gamma-H2AX phosphory 

         9 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Comt):
     behavior/neurological  cardiovascular system  embryogenesis  hematopoietic system  homeostasis/metabolism 
     immune system  nervous system  renal/urinary system  reproductive system 

    COMT for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for COMT: Comttm1Kara Comttm1Mkae

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for COMT
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for COMT

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for COMT
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for COMT

    miRNA
    Products:
        
    miRTarBase miRNAs that target COMT:
    hsa-mir-16-5p (MIRT031679)

    Block miRNA regulation of human, mouse, rat COMT using miScript Target Protectors
    8 qRT-PCR Assays for microRNAs that regulate COMT:
    hsa-miR-30c hsa-miR-513a-3p hsa-miR-30d hsa-miR-3647-3p hsa-miR-30a hsa-miR-499-5p hsa-miR-30b hsa-miR-30e
    SwitchGear 3'UTR luciferase reporter plasmidCOMT 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for COMT
    Predesigned siRNA for gene silencing in human, mouse, rat COMT

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for COMT

    Clone
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    OriGene clones in human, mouse for COMT (see all 22)
    OriGene ORF clones in mouse, rat for COMT
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 4): COMT (NM_000754)
    Sino Biological Human cDNA Clone for COMT
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for COMT
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat COMT

    Cell Line
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    GenScript Custom overexpressing Cell Line Services for COMT
    Browse ESI BIO Cell Lines and PureStem Progenitors for COMT 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for COMT


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    COMT_HUMAN, P21964: Isoform Soluble: Cytoplasm
    COMT_HUMAN, P21964: Isoform Membrane-bound: Cell membrane; Single-pass type II membrane protein; Extracellular
    side
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    cytosol4
    extracellular3
    mitochondrion2
    nucleus2
    endoplasmic reticulum1

    Gene Ontology (GO): Selected cellular component terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005739mitochondrion IEA--
    GO:0005829cytosol TAS--
    GO:0005886plasma membrane TAS--
    GO:0016020membrane ----
    GO:0016021integral component of membrane IEA--

    COMT for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for COMT About   (see all 13)  
    See pathways by source

    SuperPathContained pathways About
    1Biological oxidations
    Biological oxidations0.56
    Estradiol metabolism0.00
    Phase II conjugation0.56
    Methylation0.00
    metapathway biotransformation0.42
    Phenytoin Pathway, Pharmacokinetics0.00
    2Serotonin clearance from the synaptic cleft
    Enzymatic degradation of dopamine by COMT0.33
    Enzymatic degradation of Dopamine by monoamine oxidase0.00
    L-dopa degradation0.00
    3Estrogen metabolism
    Estrogen metabolism0.43
    Estrogen Metabolism Pathway0.43
    4Metabolism
    Metabolism0.38
    Metabolic pathways0.38
    5Phenylalanine metabolism
    Tyrosine metabolism0.36
    noradrenaline and adrenaline degradation0.31

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    3 GeneGo (Thomson Reuters) Pathways for COMT
        Tyrosine metabolism p.1 (dopamine)
    Estradiol metabolism
    Estrone metabolism

    Selected BioSystems Pathways for COMT (see all 7)
        Biogenic Amine Synthesis
    dopamine degradation
    Estrogen metabolism
    noradrenaline and adrenaline degradation
    metapathway biotransformation


    3 Reactome Pathways for COMT
        Enzymatic degradation of dopamine by COMT
    Enzymatic degradation of Dopamine by monoamine oxidase
    Methylation

    2 PharmGKB Pathways for COMT
        Estrogen Metabolism Pathway
    Phenytoin Pathway, Pharmacokinetics

    4 Kegg Pathways  (Kegg details for COMT):
        Steroid hormone biosynthesis
    Tyrosine metabolism
    Metabolic pathways
    Dopaminergic synapse


    COMT for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including COMT: 
              Amino Acid Metabolism II in human mouse rat
              Drug Metabolism: Phase II Enzymes in human mouse rat
              Molecular Toxicology PathwayFinder 384HT in human mouse rat
              Drug Metabolism in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for COMT

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for COMT (P219641, 2, 3 ENSP000003545114) via UniProtKB, MINT, STRING, and/or I2D (see all 49)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    XRN2Q9H0D61, 3, ENSP000003663964EBI-372265,EBI-372110 I2D: score=4 STRING: ENSP00000366396
    TRIP13Q156452, 3, ENSP000001663454MINT-66331 I2D: score=4 STRING: ENSP00000166345
    LITAFQ997322, 3, ENSP000003401184MINT-65288 I2D: score=4 STRING: ENSP00000340118
    RGS2P412202, 3, ENSP000002353824MINT-8268702 I2D: score=2 STRING: ENSP00000235382
    ACEP128213, ENSP000002908664I2D: score=1 STRING: ENSP00000290866
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    Gene Ontology (GO): Selected biological process terms (see all 21):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006584catecholamine metabolic process ----
    GO:0006805xenobiotic metabolic process TAS--
    GO:0007268synaptic transmission TAS--
    GO:0007565female pregnancy IEA--
    GO:0007612learning IEA--

    COMT for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Enzo Life Sciences drugs & compounds for COMT
    Selected ApexBio Compounds for COMT (see all 15)     About this table
    CompoundAction CAS #
    3-Deazaneplanocin,DZNepBlocks EZH2 activity and trimethylation of lysine 27 on histone H3 in vitro[102052-95-9]
    AZ505potent and highly selective inhibitor of the oncogenic protein SMYD2[1035227-43-0]
    BIX 01294BIX-01294 is a small molecule inhibitor of G9a and GLP[935693-62-2]
    ChaetocinHistone methyltransferase SUV39H1 inhibitor[28097-03-2]
    EntacaponeEntacapone inhibits catechol-O-methyltransferase(COMT)[130929-57-6]
    EPZ-6438potent and bio-available inhibitor of EZH2[1403254-99-8 ]
    EPZ004777potent, selective DOT1L inhibitor[1338466-77-5]
    EPZ005687potent inhibitor of EZH2[1396772-26-1]
    EPZ5676potent inhibitor of DOT1L histone methyltransferase[1380288-87-8]
    SGC 0946highly potent and selective DOT1 Lmethyltransferase inhibitor--

    Compounds for COMT available from Tocris Bioscience    About this table
    CompoundAction CAS #
    UNC 0638Selective G9a and GLP histone lysine methyltransferase inhibitor[1255517-77-1]
    BIX 01294G9a-like protein and G9a histone lysine methyltransferase inhibitor[935693-62-2]
    SGC 0946Highly potent and selective DOT1L inhibitor; cell permeable--
    3-Deazaneplanocin A hydrochlorideHistone methyltransferase inhibitor[120964-45-6]
    UNC 0646Potent and selective G9a/GLP inhibitor[1320288-17-2]

    Selected HMDB Compounds for COMT (see all 26)    About this table
    CompoundSynonyms CAS #PubMed Ids
    2-Hydroxyestradiol-3-methyl ether(17b)-3-methoxy-Estra-1,3,5(10)-triene-2,17-diol (see all 10)5976-65-811172156
    (-)-Salsoline(1S)-7-methoxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-6-ol (see all 2)89-31-6--
    2-Methoxyestrone2-(8S,9S,13S,14S)-3-hydroxy-2-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one (see all 7)362-08-3--
    3,4-Dihydroxybenzeneacetic acid(3,4-Dihydroxyphenyl)acetate (see all 23)102-32-9--
    3,4-Dihydroxymandelic acid3,4 Dihydroxymandelate (see all 7)775-01-9--
    3,4-Dihydroxyphenylglycol(3,4-Dihydroxyphenyl)ethylene glycol (see all 9)28822-73-3--
    3-Methoxytyramine3-Methoxy-4-hydroxyphenylethyl amine (see all 7)554-52-9--
    4-methoxy-17beta-estradiol4-methoxyestradiol;4-methoxy-1,3,5[10]-estratriene-3,17beta-diol;4-methoxy-3,17beta-dihydroxy-1,3,5[10]-estratriene;4-MeOE2;3,4,17beta-trihydroxy-1,3,5[10]-estratriene 4-methyl ether;3,17beta-dihydroxy-4-methoxy-1,3,5[10]-estratriene 362-07-2--
    Dopamine2-(3,4-Dihydroxyphenyl)ethylamine (see all 22)62-31-7--
    Entacaponecomtan (see all 2)130929-57-6--

    Selected DrugBank Compounds for COMT (see all 16)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    EntacaponeEntacapona [INN-Spanish] (see all 3)130929-57-6targetinhibitor12876237 11939936 11440283 10882160 10981253 11752352 9808337 11873938 10439935 12538800
    enzymeinhibitor12876237 11939936 11440283 10882160 10981253 11752352 9808337 11873938 10439935 12538800 11752352
    Tolcapone-- 134308-13-7targetinhibitor10882160 19503773 17063156 15697329 11752352 9808337 9917075 20502133 11873938 18046910 12538800
    3,5-Dinitrocatechol-- --target--17139284 17016423 10592235
    DopamineDopamin (see all 6)51-61-6enzymesubstrate15817751 21656904 21447540
    N-{3-[5-(6-Amino-Purin-9-Yl)-3,4-Dihydroxy-Tetrahydro-Furan-2-Yl]-Allyl}-2,3-Dihydroxy-5-Nitro-Benzamide-- --target--17139284 17016423 10592235
    Conjugated EstrogensEstrogens (see all 10)438-67-5enzymesubstrate20212268 20606002
    Dobutamine-- 34368-04-2enzymesubstrate11907189 2868577
    MethyldopaAlpha medopa (see all 5)555-30-6enzymesubstrate21371608 11058906
    Micafungin-- 235114-32-6enzymesubstrate15882123 17516879
    S-AdenosylmethionineAcylcarnitine (see all 6)29908-03-0targetcofactor18486144 20196537

    Selected Novoseek inferred chemical compound relationships for COMT gene (see all 108)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    entacapone 96.2 194 10492060 (6), 11865133 (4), 7874370 (3), 8665534 (3) (see all 99)
    tolcapone 95.8 161 8527287 (5), 11793426 (5), 10895397 (4), 9754991 (4) (see all 94)
    3-o-methyldopa 91.2 44 19676096 (3), 8527287 (3), 9333106 (2), 11290879 (2) (see all 23)
    levodopa 89.1 455 18698234 (5), 11290879 (5), 9591519 (4), 11147508 (4) (see all 99)
    dopamine 85.4 489 8989196 (5), 11124158 (5), 19447296 (4), 11520127 (3) (see all 99)
    carbidopa 85.2 34 15090932 (3), 19936145 (2), 10510160 (2), 8665546 (2) (see all 26)
    nitecapone 85 32 2272023 (4), 1888633 (3), 8491246 (2), 1734304 (2) (see all 16)
    maoa 83.1 72 16725119 (6), 12815746 (5), 19625011 (5), 15817751 (4) (see all 30)
    benserazide 80.2 21 14517707 (3), 19922897 (2), 10343151 (2), 9080470 (1) (see all 15)
    or486 80.1 9 15507517 (2), 11882582 (2), 18486144 (1), 17560937 (1) (see all 7)

    6 PharmGKB related drug/compound annotations for COMT gene    About this table
    Drug/compound PharmGKB Annotation
    antipsychoticsCA  
    bupropionCA  
    cisplatinCA  
    morphineCA  
    nicotineCA  
    risperidoneCA  



    COMT for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
    About This Section

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    REFSEQ mRNAs for COMT gene (4 alternative transcripts): 
    NM_000754.3  NM_001135161.1  NM_001135162.1  NM_007310.2  

    Unigene Cluster for COMT:

    Catechol-O-methyltransferase
    Hs.370408  [show with all ESTs]
    Unigene Representative Sequence: NM_000754
    11 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000361682(uc002zqu.3 uc011ahd.2 uc002zqx.3) ENST00000403184(uc021wlm.1)
    ENST00000403710(uc021wlk.1) ENST00000407537(uc021wll.1) ENST00000467943
    ENST00000412786 ENST00000207636 ENST00000406520 ENST00000493893 ENST00000428707
    ENST00000449653

    miRNA
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      QuantiFast Probe-based Assays in human, mouse, rat COMT

    Additional mRNA sequence: 

    AK129492.1 AK130031.1 AK290440.1 BC000419.2 BC005867.2 BC011935.2 BC100018.1 BT007125.1 
    CR456422.1 CR456997.1 EF103916.1 EF103917.1 EF103918.1 EF103921.1 EF103922.1 EF212883.1 
    EF217321.1 EF217322.1 FJ410131.1 FJ410132.1 M58525.1 M65212.1 

    Selected DOTS entries (see all 30):

    DT.100053173  DT.91707484  DT.100668744  DT.91985741  DT.100720599  DT.100668740  DT.100824734  DT.100824740 
    DT.87024869  DT.445233  DT.92473588  DT.91893551  DT.95279862  DT.100738288  DT.91812748  DT.97860453 
    DT.120644670  DT.120644691  DT.120644751  DT.100668741  DT.92473485  DT.100638320  DT.100771940  DT.121621671 

    Selected AceView cDNA sequences (see all 855):

    BE349135 BG413550 CR595297 BE728779 CD671083 CR603785 AW274927 BQ448204 
    CR612917 BU179805 H05760 CA842397 CB162529 Z41079 AI217499 AU279590 
    BQ073527 BQ678632 BG054676 BU839122 AI278265 CR613786 BE314182 AW768435 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for COMT (see all 8)    About this scheme

    ExUns: 1 ^ 2 ^ 3a · 3b ^ 4a · 4b ^ 5a · 5b ^ 6a · 6b ^ 7a · 7b · 7c ^ 8a · 8b ^ 9 ^ 10a · 10b
    SP1:                                -     -     -     -     -     -                 -           -               
    SP2:                                                                                            -               
    SP3:                                                                                -           -               
    SP4:              -     -                 -                                                                     
    SP5:                                      -                                                                     


    ECgene alternative splicing isoforms for COMT

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    COMT expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TTTTAAAAAT
    COMT Expression
    About this image


    COMT expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 18) fully expand
     
     Bone (Muscoskeletal System)    fully expand to see all 3 entries
             Bone Marrow
             Bone marrow-derived mesenchymal stem cells
     
     Brain (Nervous System)    fully expand to see all 3 entries
             Cerebral Cortex
     
     Mesenchymal Stem Cells
             Bone marrow-derived mesenchymal stem cells
     
     Ovary (Reproductive System)
             Ovarian Mesenchymal Stroma Cells Ovary Interstitium
     
     Thymus (Hematopoietic System)
             Thymus
    COMT Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    COMT Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.370408

    UniProtKB/Swiss-Prot: COMT_HUMAN, P21964
    Tissue specificity: Brain, liver, placenta, lymphocytes and erythrocytes

        Pathway & Disease-focused RT2 Profiler PCR Arrays including COMT: 
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              Molecular Toxicology PathwayFinder 384HT in human mouse rat
              Drug Metabolism in human mouse rat

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for COMT

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for COMT gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Comt1 , 5 catechol-O-methyltransferase1, 5 79.75(n)1
    80.58(a)1
      16 (11.40 cM)5
    128461  NM_001111062.11  NP_001104532.11 
     184073465 
    chicken
    (Gallus gallus)
    Aves COMT1 catechol-O-methyltransferase 63.81(n)
    59.66(a)
      416783  XM_001233013.3  XP_001233014.1 
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.157132 Xenopus laevis transcribed sequence with weak similarity to protein pirA38459 (H.sapiens) A38459 catechol O-methyltransferase (EC 2.1.1.6) soluble form precursor [validated] - human less 76.75(n)    CF548023.1 
    zebrafish
    (Danio rerio)
    Actinopterygii comta6
    catechol-O-methyltransferase a
    48(a)
    1 → many
    8(9004025-9025412) ENSDARG00000015337


    ENSEMBL Gene Tree for COMT (if available)
    TreeFam Gene Tree for COMT (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for COMT gene
    LRTOMT2  
    1 SIMAP similar gene for COMT using alignment to 13 protein entries:     COMT_HUMAN (see all proteins):
    LRTOMT

    COMT for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    COMT_HUMAN, P21964: Two alleles, COMT*1 or COMT*H with Val-158 and COMT*2 or COMT*L with Met-158 are responsible for a
    three to four-fold difference in enzymatic activity
    COMT_HUMAN, P21964: Low enzyme activity alleles are associated with genetic susceptibility to alcoholism [MIM:103780]


    Selected SNPs for COMT (see all 713)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 22 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs46801,2,,4
    C,F,A,Hnon-pathogenic13892513(+) CTGGCA/GTGAAG 8 M V mis156Minor allele frequency- N:0.00NA EA MN EU NS WA CSA 14731
    rs62671,2,,4
    C,F,Hother13891505(+) GGAACG/TCACAG 8 A S mis1 ese328Minor allele frequency- T:0.01NA MN NS EA EU 8572
    rs117030691,2
    H--3875756(+) catttA/Cccaat 1 -- int10--------
    rs1380780821,2
    --3875803(+) AAAAA-/TTTTTT 1 -- int10--------
    rs1746761,2
    A--3875814(+) tttagG/Tttttt 1 -- int1 trp30--------
    rs1746771,2
    C,F,A--3875850(+) gtcccG/Actgtg 1 -- int13Minor allele frequency- A:0.17NA 6
    rs1811735621,2
    --3875888(+) ATCTCA/GGCTCA 1 -- int10--------
    rs1417968301,2
    C--3875934(+) CTGCCA/TCAGCC 1 -- int10--------
    rs1746781,2
    C,F,A--3876016(+) gtttcA/Gccaca 1 -- int16Minor allele frequency- G:0.05MN NA 740
    rs1485432161,2
    --3876108(+) GTCACC/TGCGTC 1 -- int10--------

    HapMap Linkage Disequilibrium report for COMT (19929130 - 19957498 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for COMT (see all 19):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv1007918CNV Deletion20482838
    esv2723991CNV Deletion23290073
    nsv435744CNV Deletion17901297
    esv1009031CNV Deletion20482838
    esv1291604CNV Deletion17803354
    dgv4848n71CNV Loss21882294
    nsv469641CNV Loss16826518
    dgv4849n71CNV Loss21882294
    nsv914279CNV Loss21882294
    dgv4850n71CNV Loss21882294

    Human Gene Mutation Database (HGMD): COMT
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing COMT
    DNA2.0 Custom Variant and Variant Library Synthesis for COMT

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 116790   
    OMIM disorders: 181500  167870  
    Selected diseases for COMT (see all 156):    
    About MalaCards
    panic disorder    neurotic disorder    paranoid schizophrenia    schizotypal personality disorder
    cblg    impulse control disorder    parkinson disease 5    schizophrenia
    conversion disorder    alexithymia    fibromyalgia    neonatal abstinence syndrome
    personality disorder    hyperprolinemia    conduct disorder    postpartum depression
    digeorge syndrome    cannabis dependence    opiate dependence    mycetoma

    9 diseases from the University of Copenhagen DISEASES database for COMT:
    Parkinson's disease     Schizophrenia     Velocardiofacial syndrome     Attention deficit hyperactivity disorder
    Panic disorder     Substance dependence     Conduct disorder     Breast cancer
    Fibromyalgia

    COMT for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for COMT gene (see all 93)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    parkinson disease 82.1 167 9808337 (3), 10895397 (3), 15495118 (3), 11170218 (2) (see all 99)
    schizophrenia 79.6 479 17412710 (8), 12802784 (6), 19329282 (6), 16109444 (6) (see all 99)
    velo-cardio-facial syndrome 76.8 9 10490696 (1), 15645182 (1), 8950408 (1), 16511839 (1) (see all 9)
    attention-deficit hyperactivity disorder 65.7 19 19228412 (2), 17075359 (2), 19941049 (1), 10898901 (1) (see all 17)
    bipolar disorder 64.7 55 15211633 (4), 17948281 (3), 19578924 (3), 9330018 (2) (see all 33)
    velocardiofacial syndrome 64.2 9 10450274 (2), 12192614 (1), 15505638 (1), 12802784 (1) (see all 7)
    polysubstance abuse 56.7 1 11054766 (1)
    obsessive-compulsive disorder 56.7 15 11840516 (2), 17264842 (2), 10331110 (1), 12900951 (1) (see all 13)
    schizotypal personality 52.6 4 20033274 (2), 17034018 (1), 17604122 (1)
    psychiatric disorder 52.5 40 17419009 (4), 16780746 (2), 15572182 (2), 17949513 (2) (see all 29)

    Genetic Association Database (GAD): COMT
    Human Genome Epidemiology (HuGE) Navigator: COMT (932 documents)

    Export disorders for COMT gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for COMT gene, integrated from 10 sources (see all 1928):
    (articles sorted by number of sources associating them with COMT)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Catechol O-methyltransferase val158-met polymorphism is associated with abdominal obesity and blood pressure in men. (PubMed id 18442637)1, 2, 4, 9 Annerbrink K....Eriksson E. (Metabolism 2008)
    2. Crystal structures of human 108V and 108M catechol O- methyltransferase. (PubMed id 18486144)1, 2, 7, 9 Rutherford K.... Parson W.W. (J. Mol. Biol. 2008)
    3. Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans. (PubMed id 15645182)1, 2, 4, 9 Lee S.-G.... Song K. (Hum. Genet. 2005)
    4. COMT polymorphisms affecting protein expression are risk factors for endometrial cancer. (PubMed id 18324659)1, 4, 9 Hirata H....Dahiya R. (Mol. Carcinog. 2008)
    5. No association found between 158 Val/Met polymorphism of the COMT gene and schizophrenia with minor physical anomalies. (PubMed id 16109444)1, 4, 9 Joo E.J....Sik Kim Y. (Psychiatry Res 2005)
    6. The development of peripartum depressive symptoms is associated with gene polymorphisms of MAOA, 5-HTT and COMT. (PubMed id 19625011)1, 4, 9 Doornbos B....Korf J. (amp 2009)
    7. Association of the 3' region of COMT with schizophrenia in Taiwan. (PubMed id 19369177)1, 4, 9 Chien Y.L....Hwu H.G. (J. Formos. Med. Assoc. 2009)
    8. The association of functional catechol-O-methyltransferase haplotypes with risk of Parkinson's disease, levodopa treatment response, and complications. (PubMed id 18698234)1, 4, 9 Bialecka M....Drozdzik M. (Pharmacogenet. Genomics 2008)
    9. Evidence for a biopsychosocial influence on shoulder pain: pain catastrophizing and catechol-O-methyltransferase (COMT) diplotype predict clinical pain ratings. (PubMed id 17686583)1, 4, 9 George S.Z....Fillingim R.B. (Pain 2008)
    10. Genetic variation in COMT and PRODH is associated with brain anatomy in patients with schizophrenia. (PubMed id 17504246)1, 4, 9 Zinkstok J....Linszen D. (Genes Brain Behav. 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 1312 HGNC: 2228 AceView: COMT Ensembl:ENSG00000093010 euGenes: HUgn1312
    ECgene: COMT Kegg: 1312 H-InvDB: COMT

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for COMT Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for COMT Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPshttp://egp.gs.washington.edu/data/comt/
    Wikipedia http://en.wikipedia.org/wiki/Catechol-O-methyl_transferase

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for COMT gene:
    Search GeneIP for patents involving COMT

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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