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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

COMT Gene

protein-coding GIFtS: 74
GCID: GC22P019929

catechol-O-methyltransferase

Explore 164 diseases affiliated with
COMT via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Catechol-O-Methyltransferase¹
EC 2.1.1.6³ ⁸
Catechol O-Methyltransferase²

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, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for COMT:

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)

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:

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)

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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000022.10 NC_018933.1 NT_011519.10

Regulatory elements:

SABiosciences 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 SABiosciences Chromatin IP Primers for COMT

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

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

Subcellular location: Isoform Soluble: Cytoplasm

Subcellular location: Isoform Membrane-bound: Cell membrane; Single-pass type II membrane protein; Extracellular side

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

Post-translational modifications:

The N-terminus is blocked¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P21964

3 DME Specific Peptides for COMT (P21964)

GTVLLADNVI

LLLEECGLLR

LELGAYCGYSAVRMARLL

COMT Protein expression data from MOPED and PaxDb: About this image

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
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: COMT OriGene Protein Over-expression Lysate: 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
	ProSpec Recombinant Protein for COMT
	Uscn Proteins for COMT

Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (see all 8): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005624	membrane fraction	--	--
GO:0005625	soluble fraction	--	--
GO:0005739	mitochondrion	IEA	--
GO:0005792	microsome	--	--
GO:0005829	cytosol	TAS	--

COMT for ontologies About GeneDecksing

COMT Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of COMT
	R&D Systems Antibodies for COMT
	OriGene Antibodies (see all 3): COMT OriGene Custom Antibody Services for COMT
	GenScript Custom Superior Antibodies Services for COMT
	Novus Biologicals COMT Antibodies
	Abcam antibodies for COMT
	Uscn Antibodies for COMT
	ThermoFisher Antibody for COMT

Assay Products for COMT:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for COMT
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for COMT

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

COMT for domains About GeneDecksing

3 InterPro domains/families:

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 family: IPB002935 O-methyltransferase

UniProtKB/Swiss-Prot: COMT_HUMAN, P21964

Similarity: Belongs to the mammalian catechol-O-methyltransferase family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

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

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

miRNA Products:		OriGene 3'-UTR Clone (see all 4): COMT Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat COMT
		8 QIAGEN miScript miRNA 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 plasmid: COMT 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for COMT (see all 7) OriGene shRNA RFP: COMT OriGene siRNA: COMT
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat COMT

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for COMT

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
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		GenScript: all cDNA clones in your preferred vector (see all 4): COMT (NM_000754)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for COMT
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat COMT

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for COMT
		Search LifeMap BioReagents cell lines for COMT

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for COMT

Gene Ontology (GO): 3 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000287	magnesium ion binding	IEA	--
GO:0008171	O-methyltransferase activity	TAS	1707278
GO:0016206	catechol O-methyltransferase activity	IEA	--

COMT for ontologies About GeneDecksing

1 GenomeRNAi human phenotype for COMT:

Increased gamma-H2AX phosphory

Animal Models:
Mouse knock-outs for COMT: Comt^tm1Kara Comt^tm1Mkae
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

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/13 super-pathways (see all 13) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Enzymatic degradation of dopamine by COMT

Enzymatic degradation of dopamine by COMT	1.00	L-dopa degradation	0.50
Enzymatic degradation of Dopamine by monoamine oxidase	1.00	Neurotransmitter Clearance In The Synaptic Cleft	0.29
Dopamine clearance from the synaptic cleft	0.67

Tyrosine metabolism

	Tyrosine metabolism	1.00			Tyrosine metabolism p.1 (dopamine)	0.28
	Tyrosine metabolism p.1 (dopamine)	0.28

Biological oxidations

	Biological oxidations	1.00			metapathway biotransformation	0.41
	Phase II conjugation	0.52

Transmission across Chemical Synapses

Transmission across Chemical Synapses

1.00

Neuronal System

0.67

Metabolism

Metabolism

1.00

Metabolic pathways

0.38

Pathway sources
See GeneCards unified pathways
Show all pathways

3 EMD Millipore Pathways for COMT

	Estradiol metabolism
	Tyrosine metabolism p.1 (dopamine)
	Estrone metabolism

3 GeneGo (Thomson Reuters) Pathways for COMT

	Tyrosine metabolism p.1 (dopamine)
	Estradiol metabolism
	Estrone metabolism

5/6 BioSystems Pathways for COMT (see all 6)

	Biogenic Amine Synthesis
	dopamine degradation
	Estrogen metabolism
	noradrenaline and adrenaline degradation
	L-dopa degradation

5/10 Reactome Pathways for COMT (see all 10)

	Enzymatic degradation of dopamine by COMT
	Enzymatic degradation of Dopamine by monoamine oxidase
	Transmission across Chemical Synapses
	Metabolism
	Dopamine clearance from the synaptic cleft

2 PharmGKB Pathways for COMT

	Estrogen Metabolism Pathway
	Phenytoin Pathway, Pharmacokinetics

3 Kegg Pathways (Kegg details for COMT):

	Steroid hormone biosynthesis
	Tyrosine metabolism
	Metabolic pathways

COMT for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for COMT

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

5/49 Interacting proteins for COMT (P21964^{1, 2, 3} ENSP00000354511⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 49)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
XRN2	Q9H0D6¹^,³, ENSP00000366396⁴	EBI-372265,EBI-372110 I2D: score=4 STRING: ENSP00000366396
TRIP13	Q15645²^,³, ENSP00000166345⁴	MINT-66331 I2D: score=4 STRING: ENSP00000166345
LITAF	Q99732²^,³, ENSP00000340118⁴	MINT-65288 I2D: score=4 STRING: ENSP00000340118
RGS2	P41220²^,³, ENSP00000235382⁴	MINT-8268702 I2D: score=2 STRING: ENSP00000235382
ACE	P12821³, ENSP00000290866⁴	I2D: score=1 STRING: ENSP00000290866

About this table

Gene Ontology (GO): 5/21 biological process terms (GO ID links to tree view) (see all 21): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006584	catecholamine metabolic process	--	--
GO:0006805	xenobiotic metabolic process	TAS	--
GO:0007268	synaptic transmission	TAS	--
GO:0007565	female pregnancy	IEA	--
GO:0007612	learning	IEA	--

COMT for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

COMT for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Enzo Life Sciences drugs & compounds for COMT

Compounds for COMT available from Tocris Bioscience About this table

Compound	Action	CAS #
OR-486	Catechol-O-methyl transferase inhibitor	[7659-29-2]

10/26 HMDB Compounds for COMT (see all 26) About this table

Compound	Synonyms	CAS #	PubMed Ids
2-Hydroxyestradiol-3-methyl ether	(17b)-3-methoxy-Estra-1,3,5(10)-triene-2,17-diol (see all 10)	5976-65-8	11172156
(-)-Salsoline	(1S)-7-methoxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-6-ol (see all 2)	89-31-6	--
2-Methoxyestrone	2-(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 acid	3,4 Dihydroxymandelate (see all 7)	775-01-9	--
3,4-Dihydroxyphenylglycol	(3,4-Dihydroxyphenyl)ethylene glycol (see all 9)	28822-73-3	--
3-Methoxytyramine	3-Methoxy-4-hydroxyphenylethyl amine (see all 7)	554-52-9	--
4-methoxy-17beta-estradiol	4-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	--
Dopamine	2-(3,4-Dihydroxyphenyl)ethylamine (see all 22)	62-31-7	--
Entacapone	comtan (see all 2)	130929-57-6	--

10/15 DrugBank Compounds for COMT (see all 15) About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Entacapone	Entacapona [INN-Spanish] (see all 3)	130929-57-6	target	inhibitor	12876237 11939936 11440283 10882160 10981253 11752352 9808337 11873938 10439935 12538800
Entacapone	Entacapona [INN-Spanish] (see all 3)	130929-57-6	enzyme	inhibitor	12876237 11939936 11440283 10882160 10981253 11752352 9808337 11873938 10439935 12538800 11752352
Tolcapone	--	134308-13-7	target	inhibitor	10882160 19503773 17063156 15697329 11752352 9808337 9917075 20502133 11873938 18046910 12538800
3,5-Dinitrocatechol	--	--	target	--	17139284 17016423 10592235
Dopamine	Dopamin (see all 6)	51-61-6	enzyme	substrate	15817751 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 Estrogens	Estrogens (see all 10)	438-67-5	enzyme	substrate	20212268 20606002
Dobutamine	--	34368-04-2	enzyme	substrate	11907189 2868577
Methyldopa	Alpha medopa (see all 5)	555-30-6	enzyme	substrate	21371608 11058906
Micafungin	--	235114-32-6	enzyme	substrate	15882123 17516879
S-Adenosylmethionine	Acylcarnitine (see all 6)	29908-03-0	target	cofactor	18486144 20196537

10/108 Novoseek 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

Drug/compound	PharmGKB Annotation
antipsychotics	CA
bupropion	CA
cisplatin	CA
morphine	CA
nicotine	CA
risperidone	CA

About this table

Search CenterWatch for drugs/clinical trials and news about COMT

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for COMT gene (4 alternative transcripts):

NM_000754.3 NM_001135161.1 NM_001135162.1 NM_007310.2

Unigene Clusters for COMT:

Catechol-O-methyltransferase

Hs.370408 [show with all ESTs], Hs.713616 [show with all ESTs]

Unigene Representative Sequences: NM_000754, NM_001670

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 Products:		OriGene 3'-UTR Clone (see all 4): COMT Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat COMT
		8 QIAGEN miScript miRNA 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 plasmid: COMT 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for COMT (see all 7) OriGene shRNA RFP: COMT OriGene siRNA: COMT
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat COMT

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for COMT (see all 8) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for COMT (see all 5) 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)
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		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat COMT

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		SABiosciences RT² qPCR Primer Assay in human, mouse, rat COMT
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat COMT
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat COMT

Additional cDNA sequence:

AK092664.1 AL390148.1 BC005092.1 BC036893.1 BC137436.1 M65213.1 U51269.1

24/45 DOTS entries (see all 45):

DT.100053173 DT.91707484 DT.100720599 DT.91985741 DT.100668744 DT.100824734 DT.100668740 DT.445233

DT.91827051 DT.100778546 DT.100824740 DT.87024869 DT.92067937 DT.92473588 DT.91893551 DT.95279862

DT.100738288 DT.97769223 DT.70102245 DT.91812748 DT.97860453 DT.100027592 DT.120644670 DT.120644691

24/855 AceView cDNA sequences (see all 855):

AA349631 BU151565 CR624969 NM_000754 CB162529 CR613786 BQ682461 BE314182

AI184699 BI826013 CR625831 BQ073527 BE728779 BE729790 CR610047 BQ681835

BU558101 AI278265 BU839122 BQ680321 BE410186 BF724444 AW768435 AI913966

GeneLoc Exon Structure

5/8 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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

COMT expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TTTTAAAAAT

About this image

COMT expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

Stem Cell Differentiation: 5 LifeMap Cells

Name

Category

PureStem™ endothelial progenitor 30-SM2-1 (Embryonic Progenitor Cell)

Endothelium

PureStem™ endothelial progenitor RP1-MV2-18 (Embryonic Progenitor Cell)

Endothelium

PureStem™ endothelial progenitor 30-MV2-14 (Embryonic Progenitor Cell)

Endothelium

PureStem™ progenitor W10 (Embryonic Progenitor Cell)

PureStem™ progenitor W8 (Embryonic Progenitor Cell)

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See COMT Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for COMT

SOURCE GeneReport for Unigene clusters: Hs.370408 Hs.713616

UniProtKB/Swiss-Prot: COMT_HUMAN, P21964

Tissue specificity: Brain, liver, placenta, lymphocytes and erythrocytes

SABiosciences Expression via Pathway-Focused 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

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for COMT Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat COMT
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat COMT
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat COMT

In Situ
Assay Products:

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)
About This Section

This gene was present in the common ancestor of chordates.

Orthologs for COMT gene from 4/17 species (see all 17) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Details
mouse (Mus musculus)	Mammalia	Comt^{1 , 5}	catechol-O-methyltransferase^{1, 5}	79.49(n)¹ 80.38(a)¹	16 (11.40 cM)⁵ 12846¹ NM_001111062.1¹ NP_001104532.1¹ 18407346⁵
chicken (Gallus gallus)	Aves	COMT¹	catechol-O-methyltransferase	62.09(n) 56.11(a)	416783 XM_001233013.2 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	comtb¹	catechol-O-methyltransferase b	58.69(n) 53.33(a)	565370 NM_001083843.1 NP_001077312.1

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)
About This Section

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, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

UniProtKB/Swiss-Prot: COMT_HUMAN, P21964

Polymorphism: 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

Polymorphism: Low enzyme activity alleles are associated with genetic susceptibility to alcoholism [MIM:103780]

SNP ID	Valid	Clinical significance	Chr 22 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs4680^1,2	C,F,A,H,	non-pathogenic	19951271(+)	`CTGGCA/GTGAAG`	9	M V	mis¹ us2k¹		56		NA EA MN EU NS WA CSA	14731
rs6267^1,2	C,F,H,	other	19950263(+)	`GGAACG/TCACAG`	9	A S	mis¹ us2k¹ ese³		28		NA MN NS EA EU	8572
rs114214004^1,2	F,	--	19927287(+)	`CTATAG/TGGAAA`	2	--	int¹ us2k¹		1		WA	118
rs187264383^1,2		--	19927437(+)	`CAATTG/TGGGAA`	2	--	us2k¹ int¹		0	--	--	--	--
rs140522525^1,2		--	19927468(+)	`CAGTAA/GTATTA`	2	--	int¹ us2k¹		0	--	--	--	--
rs191409258^1,2		--	19927594(+)	`ATCCCA/GTCTCT`	2	--	int¹ us2k¹		0	--	--	--	--
rs5992496^1,2	C	--	19927658(+)	`agctaC/Atcggg`	2	--	us2k¹ int¹		2		NS NA	180
rs5992497^1,2	C	--	19927659(+)	`gctacT/Ccggga`	2	--	int¹ us2k¹		2		NS NA	180
rs9332311^1,2	C,F,	--	19927693(+)	`AACCCG/AGGAGG`	2	--	int¹ us2k¹		3		NS NA	182
rs9332312^1,2	C,F,	--	19927925(+)	`atcatC/Tatcct`	2	--	us2k¹ int¹		2		NS NA	178

HapMap Linkage Disequilibrium report for COMT (19929130 - 19957498 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 3 variations for COMT
3 CNVs: 2261 5168 31071
Human Gene Mutation Database (HGMD): COMT

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat 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, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

COMT for disorders           About GeneDecksing

OMIM gene information: 116790
OMIM disorders: 181500  167870
20/164 diseases for COMT (see all 164):    About MalaCards

schizotypal personality disorder parkinson's disease attention deficit hyperactivity disorder hypertension

personality disorder migraine without aura asthma antisocial personality disorder

bulimia nervosa panic disorder borderline personality disorder paranoid schizophrenia

restless legs syndrome pre-eclampsia alcohol abuse phobia

9 diseases from the University of Copenhagen DISEASES database for COMT:

Schizophrenia Parkinson's disease Attention deficit hyperactivity disorder Velocardiofacial syndrome

Conduct disorder Breast cancer Substance dependence Panic disorder

Fibromyalgia

10/93 Novoseek 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)
About This Section

PubMed articles for COMT gene, integrated from 9 sources (see all 1800):
(articles sorted by number of sources associating them with COMT)

Utopia: connect your pdf to the dynamic
world of online information

Crystal structures of human 108V and 108M catechol O- methyltransferase. (PubMed id 18486144)^{1, 2, 7, 9} Rutherford K.... Parson W.W. (2008)
Analysis of an association between the COMT polymorphism and clinical symptomatology in schizophrenia. (PubMed id 16233957)^{1, 4, 9} Strous R.D....Lachman H.M. (2006)
[Association study of heroin dependence and catechol-O-methyltransferase gene] (PubMed id 12673581)^{1, 4, 9} Cao L....Liu X. (2003)
Association analysis of MAOA and COMT with neuroticism assessed by peers. (PubMed id 12815746)^{1, 4, 9} Eley T.C....Craig I. (2003)
A highly significant association between a COMT haplotype and schizophrenia. (PubMed id 12402217)^{1, 4, 9} Shifman S....Darvasi A. (2002)
Catechol-O-methyltransferase gene polymorphism in schizophrenia: evidence for association between symptomatology and prognosis. (PubMed id 11525417)^{1, 4, 9} Herken H. and Erdal M.E. (2001)
Catechol-O-methyltransferase polymorphism is not associated with ovarian cancer risk. (PubMed id 11142424)^{1, 4, 9} Goodman J.E....Yager J.D. (2000)
Interaction between NOTCH4 and catechol-O-methyltransferase genotypes in schizophrenia patients with poor response to typical neuroleptics. (PubMed id 15115916)^{1, 4, 9} Anttila S....Leinonen E. (2004)
[No evidence for gender-specific sharing of COMT alleles in schizophrenia] (PubMed id 15570503)^{1, 4, 9} Sand P....Eichhammer P. (2004)
MAO-A and COMT polymorphisms and gene effects in narcolepsy. (PubMed id 11443519)^{1, 4, 9} Dauvilliers Y....Tafti M. (2001)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
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)
About This Section

Entrez Gene: 1312	HGNC: 2228	AceView: COMT	Ensembl:ENSG00000093010	euGenes: HUgn1312
ECgene: COMT	Kegg: 1312	H-InvDB: COMT

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for COMT	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for COMT	Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs	http://egp.gs.washington.edu/data/comt/
Wikipedia	http://en.wikipedia.org/wiki/Catechol-O-methyl_transferase

Intellectual Property for COMT gene
(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

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences),
In Situ Hybridization Assays from
Advanced Cell Diagnostics
About This Section

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catechol-O-methyltransferase

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COMT Gene

catechol-O-methyltransferase

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