Gene Report

Basic Information

Approved Symbol	COMT
Approved Name	catechol-O-methyltransferase
Location	22q11.21
Position	chr22:19929263-19957498 (+)
External Links	Entrez Gene: 1312 Ensembl: ENSG00000093010 UCSC: uc002zqu.3 HGNC ID: 2228
No. of Studies (Positive/Negative)	6(6/0)
Type	Literature-origin; SNP mapped

Positive relationships between COMT and MDD (count: 3)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
COMT	Kocabas, 2010	patients and normal controls	P-value<0.01	The combinations of G-T-G-G haplotype for rs6269, rs4633, rs...... The combinations of G-T-G-G haplotype for rs6269, rs4633, rs4818 and rs4680 were only present in the MDD group (G-T 4.5%, corrected sim P=0.0001; G-T-G 3.87%, corrected sim P=0.001; G-T-G-G 3.3% corrected sim P=0.0025). More...
COMT	Mandelli L, 2007	Patients and nomal controls	chi2=13.05, d.f.=2, p=0.0015	COMT was associated with depression following exposure to s...... COMT was associated with depression following exposure to stressors (chi2=13.05, d.f.=2, p=0.0015) and SERTPR also showed a positive association (chi2=6.70, d.f.=2, p=0.035), mainly among women and among major depressives. The interaction between COMT and SERTPR was also significant (p=0.0005). More...
COMT	Aberg E, 2011	Patients and nomal controls	OR=1.49, CI(95%)=1.11-2.00, P=0.009	Depressed individuals displayed a higher frequency of the Me...... Depressed individuals displayed a higher frequency of the Met/Met and Met/Val genotypes compared to controls (OR=1.49, CI(95%)=1.11-2.00, P=0.009). More...

Positive relationships between COMT and other components at different levels (count: 8)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description
Name in Literature	Related Components
COMT		SLC6A4(serotonin transporter gene (SERTPR))	gene	Mandelli L, 2007	Patients and nomal controls	p=0.0005	COMT was associated with depression following exposure to s...... COMT was associated with depression following exposure to stressors (chi2=13.05, d.f.=2, p=0.0015) and SERTPR also showed a positive association (chi2=6.70, d.f.=2, p=0.035), mainly among women and among major depressives. The interaction between COMT and SERTPR was also significant (p=0.0005). More...
catechol-o-methyltransferase		Hydrocortisone(cortisol)	molecule	Jabbi, 2007	patients and normal controls		Interactions between catechol-o-methyltransferase polymorphi...... Interactions between catechol-o-methyltransferase polymorphism and diagnostic group in measures of plasma epinephrine, cortisol and subjective responses to psychological stress were also found More...
catechol-o-methyltransferase		Epinephrine(epinephrine)	molecule	Jabbi, 2007	patients and normal controls		Interactions between catechol-o-methyltransferase polymorphi...... Interactions between catechol-o-methyltransferase polymorphism and diagnostic group in measures of plasma epinephrine, cortisol and subjective responses to psychological stress were also found More...
catechol-O-methyltransferase (COMT)		Basal ganglia(basal ganglia)	brain morphology and function	Dillon, 2010	normal people		Results revealed that TREK1 and DAT/COMT genotypes were inde...... Results revealed that TREK1 and DAT/COMT genotypes were independently related to basal ganglia responses to gains. More...
catechol-O-methyltransferase (COMT)		Amygdala(amygdala)	brain morphology and function	Lelli-Chiesa, 2011	patients and normal controls		the Val158 allele was associated with greater amygdala activ...... the Val158 allele was associated with greater amygdala activation More...
catechol-O-methyltransferase (COMT)		ventrolateral prefrontal cortex(ventrolateral PFC (vlPFC))	brain morphology and function	Lelli-Chiesa, 2011	patients and normal controls		the Met158 allele with greater signal change in the vlPFC the Met158 allele with greater signal change in the vlPFC
catechol-O-methyltransferase (COMT)		ventromedial prefrontal cortex(ventromedial PFC (vmPFC))	brain morphology and function	Lelli-Chiesa, 2011	patients and normal controls		the Met158 allele with greater signal change in the vmPFC the Met158 allele with greater signal change in the vmPFC
catechol-o-methyltransferase		Subjective responses to psychological stress(subjective responses to psychological stress)	cognition and behavior	Jabbi, 2007	patients and normal controls		Allelic variations of this polymorphism were found to influe...... Allelic variations of this polymorphism were found to influence the degree of subjective stress experience and plasma epinephrine stress response. Interactions between catechol-o-methyltransferase polymorphism and diagnostic group in measures of plasma epinephrine, cortisol and subjective responses to psychological stress were also found More...

Positive relationship network of COMT in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between COMT and MDD (count: 0)

Negative relationships between COMT and other components at different levels (count: 0)

COMT related SNPs in MK4MDD (count: 1)

#rs	Location	Annotation	No. of Studies (Positive/Negative)
rs4680	chr22:19951271(Forward)	downstream_gene_variant; missense_variant; nc_transcript_variant; NMD_transcript_variant; non_coding_exon_variant; upstream_gene_variant	3(2/1)

COMT related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Catechol O-methyltransferase	P21964	0(0/0)	Gene mapped

COMT related GO terms (count: 26)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0007268	synaptic transmission	biological process	TAS

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0045963	negative regulation of dopamine metabolic process	biological process	IEA
GO:0006805	xenobiotic metabolic process	biological process	TAS
GO:0016206	catechol O-methyltransferase activity	molecular function	IEA
GO:0042420	dopamine catabolic process	biological process	IEA
GO:0008210	estrogen metabolic process	biological process	IEA
GO:0043231	intracellular membrane-bounded organelle	cellular component	IDA
GO:0014070	response to organic cyclic compound	biological process	IEA
GO:0007612	learning	biological process	IEA
GO:0000287	magnesium ion binding	molecular function	IEA
GO:0042136	neurotransmitter biosynthetic process	biological process	TAS
GO:0005739	mitochondrion	cellular component	IEA
GO:0032259	methylation	biological process	TAS
GO:0007565	female pregnancy	biological process	IEA
GO:0042135	neurotransmitter catabolic process	biological process	IEA
GO:0048609	multicellular organismal reproductive process	biological process	IEA
GO:0005829	cytosol	cellular component	TAS
GO:0032496	response to lipopolysaccharide	biological process	IEA
GO:0048265	response to pain	biological process	IEA
GO:0005886	plasma membrane	cellular component	TAS
GO:0048662	negative regulation of smooth muscle cell proliferation	biological process	IEA
GO:0050668	positive regulation of homocysteine metabolic process	biological process	IEA
GO:0044281	small molecule metabolic process	biological process	TAS
GO:0042493	response to drug	biological process	IEA
GO:0008171	O-methyltransferase activity	molecular function	TAS[1707278]
GO:0016021	integral to membrane	cellular component	IEA

COMT related KEGG pathways (count: 2)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa00350	tyrosine metabolism	Tyrosine metabolism
hsa00140	steroid hormone_biosynthesis	Steroid hormone biosynthesis	Steroid hormones derived from cholesterol are a class of bio...... Steroid hormones derived from cholesterol are a class of biologically active compounds in vertebrates. The cholesterol side-chain cleavage enzyme CYP11A1 catalyzes conversion of cholesterol, a C27 compound, to the first C21 steroid, pregnenolone, which is converted by a bifunctional enzyme complex to the gestagen hormone, progesterone. Pregnenolone and progesterone are the starting materials for the three groups of steroids: C21 steroids of glucocorticoids and mineralocorticoids, C19 steroids of androgens, and C18 steroids of estrogens. (i) Progesterone is converted by hydroxylations at carbons 21 and 11 to corticosterone, which is further modified by hydroxylation and oxydoreduction at carbon 18 to yield aldosterone, a mineralcorticoid. Cortisol, the main glucocorticoid, is formed from 17alpha-hydroxyprogesterone with 11-deoxycortisol as an intermediate. (ii) Male hormone testosterone is formed from pregnenolone by two pathways, delta5 pathway via dehydroepiandrosterone and delta4 pathway via androstenedione. The enzyme CYP17A1 is responsible for the 17,20 lyase and 17alpha-hydroxylase activities in respective pathways. (iii) Female hormones estrone and estradiol are formed from testosterone and 4-androstene-3,17-dione by oxidative removal of the C19 methyl group and subsequent aromatization of ring A. In addition to these three groups, recent studies show that there is another group, termed neurosteroids, synthesized in the brain rather than the peripheral endocrine gland. More...

COMT related BioCarta pathways (count: 0)

COMT related Reactome pathways (count: 3)

ID	Name	Description
Gene mapped Reactome pathways
REACT_6959	phase ii_conjugation	Phase II of biotransformation is concerned with conjugation,...... Phase II of biotransformation is concerned with conjugation, that is using groups from cofactors to react with functional groups present or introduced from phase I on the compound. The enzymes involved are a set of transferases which perform the transfer of the cofactor group to the substrate. The resultant conjugation results in greatly increasing the excretory potential of compounds. Although most conjugations result in pharmacological inactivation or detoxification, some can result in bioactivation. Most of the phase II enzymes are located in the cytosol except UDP-glucuronosyltransferases (UGT), which are microsomal. Phase II reactions are typically much faster than phase I reactions therefore the rate-limiting step for biotransformation of a compound is usually the phase I reaction. Phase II metabolism can deal with all the products of phase I metabolism, be they reactive (Type I substrate) or unreactive/poorly active (Type II substrate) compounds. With the exception of glutathione, the conjugating species needs to be made chemically reactive after synthesis. The availability of the cofactor in the synthesis may be a rate-limiting factor in some phase II pathways as it may prevent the formation of enough conjugating species to deal with the substrate or it's metabolite. As many substrates and/or their metabolites are chemically reactive, their continued presence may lead to toxicity. More...
REACT_13433	biological oxidations	All organisms are constantly exposed to foreign chemicals ev...... All organisms are constantly exposed to foreign chemicals every day. These can be man-made. Once chemicals undergo functionalization, the electrophilic or nucleophilic species can be detrimental to biological systems. Electrophiles can react with electron-rich macromolecules such as proteins, DNA and RNA by covalent interaction whilst nucleophiles have the potential to interact with biological receptors. That's why conjugation is so important as it mops up these potentially reactive species. Many chemicals, when exposed to certain metabolizing enzymes can induce those enzymes, a process called enzyme induction. The effect of this is that these chemicals accelerate their own biotransformation and excretion. The reverse is also true where some chemicals cause enzyme inhibition. Some other factors that alter enzyme levels are sex, age and genetic predisposition. Between species, there can be considerable differences in biotransformation ability which is a problem faced by drug researchers interpreting toxicological results to humans. More...
REACT_13477	transmission across_chemical_synapses	Chemical synapses are specialized junctions that are used fo...... Chemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron, muscle cell or glad cell. The pre and the post-synaptic cell are separated by a gap of 20nm called the synaptic cleft. The signals pass in a unidirection from pre-synaptic to post-synaptic. The pre-synaptic neuron communicates via the release of neurotransmitter which bind the receptors on the post-synaptic cell. More...

COMT related interactors from protein-protein interaction data in HPRD (count: 4)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
COMT	LITAF	Yes	yeast 2-hybrid	16169070
COMT	XRN2	No	yeast 2-hybrid	15231747
COMT	TRIP13	No	yeast 2-hybrid	16189514
COMT	ACE	Yes	in vivo	12729939

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped Reactome pathways