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FLASH GENE

Symbol

COMT

contributors: mct/npt/pgu - updated : 05-04-2013

HGNC name	catechol-O-methyltransferase
HGNC id	2228

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	SCZD4 schizophrenia 4
Location	22q11.21      Physical location : 19.929.262 - 19.957.496
Synonym symbol(s)	COMT1
EC.number	2.1.1.6

DNA

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001135161 6 initiation site 2262 NP_001128633 30 271 - 2011 21846718 long 5'utr NM_007310 4 initiation site 2035 NP_009294 - 221 - 2011 21846718 variant 4 - S-COMT, soluble short 5'utr downstream initiation site subcellular localization: intracellular, cytoplasm, cytosol, microsome NM_000754 6 - 2304 NP_000745 - 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 NM_001135162 6 - 2279 NP_001128634 30 271 - 2011 21846718

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic erthrocyte Lymphoid/Immune lymphocyte Nervous neuron

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, pregnancy

Text	placenta, marginal zone and cortical plate

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

Homologene

FAMILY

mammalian catechol-O-methyltransferase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,cytosolic

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

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

aminoacid , drug

signaling

neurotransmission

tyrosine, catechol drugs

a component

INTERACTION

DNA

RNA

small molecule

protein	regulating SLC6A3
	interaction of BDNF by COMT on human cortical plasticity

cell & other

REGULATION

inhibited by

serotonin

ASSOCIATED DISORDERS

corresponding disease(s)

SCZD4

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional   deletion     hemizygous deletion in 22q11 microdeletion syndromes (velocardiofacial syndrome [VCFS] or DiGeorge syndrome [DGS])

Susceptibility

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
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous pain   inhibition of COMT via serotonin binding contributes to pain hypersensitivity, providing additional strategies for the treatment of clinical pain conditions neurology     promising target for modulation of cognitive functions and dysfunctions

ANIMAL & CELL MODELS

	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