Comt catechol-O-methyltransferase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Comtprovided by MGI
Official Full Name: catechol-O-methyltransferaseprovided by MGI
Primary source: MGI:MGI:88470
See related: Ensembl:ENSMUSG00000000326 AllianceGenome:MGI:88470
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Comt1; D16Wsu103e; D330014B15Rik
Summary: Enables catechol O-methyltransferase activity. Acts upstream of or within several processes, including catecholamine metabolic process; learning or memory; and signal release. Located in mitochondrion. Is active in cytosol and vesicle. Is expressed in several structures, including alimentary system; central nervous system; genitourinary system; hemolymphoid system; and sensory organ. Used to study cognitive disorder and pre-eclampsia. Human ortholog(s) of this gene implicated in several diseases, including autoimmune disease of skin and connective tissue (multiple); cognitive disorder (multiple); drug dependence (multiple); reproductive organ cancer (multiple); and withdrawal disorder (multiple). Orthologous to human COMT (catechol-O-methyltransferase). [provided by Alliance of Genome Resources, Apr 2025]
Expression: Broad expression in liver adult (RPKM 254.4), subcutaneous fat pad adult (RPKM 175.4) and 25 other tissues See more
Orthologs: human all
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Genomic context

Location:: 16 A3; 16 11.4 cM

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	16	NC_000082.7 (18225632..18247006, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	16	NC_000082.6 (18406882..18426716, complement)

Chromosome 16 - NC_000082.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Dysregulated COMT Expression in Fragile X Syndrome.
Title: Dysregulated COMT Expression in Fragile X Syndrome.
Catechol-O-Methyltransferase Loss Drives Cell-Specific Nociceptive Signaling via the Enteric Catechol-O-Methyltransferase/microRNA-155/Tumor Necrosis Factor alpha Axis.
Title: Catechol-O-Methyltransferase Loss Drives Cell-Specific Nociceptive Signaling via the Enteric Catechol-O-Methyltransferase/microRNA-155/Tumor Necrosis Factor α Axis.
Dietary Magnesium Insufficiency Induces Salt-Sensitive Hypertension in Mice Associated With Reduced Kidney Catechol-O-Methyl Transferase Activity.
Title: Dietary Magnesium Insufficiency Induces Salt-Sensitive Hypertension in Mice Associated With Reduced Kidney Catechol-O-Methyl Transferase Activity.
desmocollin-1 (DSC1) is validated as a protein connected with lymph node status of luminal A breast cancer, tumor grade, and Her-2 status and catechol-O-methyltransferase is successfully verified as a protein associated with lymph node metastasis of triple negative breast cancer.
Title: Proteomics Identification and Validation of Desmocollin-1 and Catechol-O-Methyltransferase as Proteins Associated with Breast Cancer Cell Migration and Metastasis.
These results suggest that COMT is an enzyme to maintain glucose homeostasis and 2-methoxyestradiol is a potential endogenous multi-target anti-diabetic candidate.
Title: Deficiency in catechol-o-methyltransferase is linked to a disruption of glucose homeostasis in mice.
Miroestrol restored uterine COMT expression in beta-naphthoflavone-treated mice.
Title: Regulation of cancer-related genes - Cyp1a1, Cyp1b1, Cyp19, Nqo1 and Comt - expression in β-naphthoflavone-treated mice by miroestrol.
This study report that genetically driven reduction in COMT enzyme activity increased cortical thickness in the prefrontal cortex (PFC) and postero-parieto-temporal cortex of male, but not female adult mice.
Title: COMT Genetic Reduction Produces Sexually Divergent Effects on Cortical Anatomy and Working Memory in Mice and Humans.
COMT expression in the hippocampus was significantly reduced by high E2 replacement, implying increased catecholamine levels in the hippocampus of high E2 mice.
Title: Estradiol replacement enhances fear memory formation, impairs extinction and reduces COMT expression levels in the hippocampus of ovariectomized female mice.
COMT overexpressing mice display an increase in dopamine release capacity in the striatum, suggesting increased COMT activity may affect dopamine signaling by enhancing synaptic clearance in the cortex and changes in striatal presynaptic dopamine function
Title: Genetic variation in COMT activity impacts learning and dopamine release capacity in the striatum.
These data confirm at the level of mouse working memory and human working memory-associated physiology a genetic interaction between COMT and DTNBP1.
Title: Epistatic interaction between COMT and DTNBP1 modulates prefrontal function in mice and in humans.

Submit: New GeneRIF Correction See all GeneRIFs (29)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (3)
Spontaneous (1) 1 citation
Targeted (8) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D16Jhu32 (e-PCR), detects polymorphism
- UniSTS:142080

RH125710 (e-PCR)
- UniSTS:142094

AF076156 (e-PCR)
- UniSTS:209176

D9Mit34.1 (e-PCR), detects polymorphism
- UniSTS:131903

Comt (e-PCR), detects polymorphism
- UniSTS:496796

Comt (e-PCR), detects polymorphism
- UniSTS:506809

Comt (e-PCR), detects polymorphism
- UniSTS:265697

Comt (e-PCR), detects polymorphism
- UniSTS:265698

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables catechol O-methyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables catechol O-methyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables catechol O-methyltransferase activity	ISO Inferred from Sequence Orthology more info
enables magnesium ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within artery development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within behavior	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within behavioral fear response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in catecholamine catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in catecholamine catabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within catecholamine metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to cocaine	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to phosphate starvation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cerebellar cortex morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cholesterol efflux	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cognition	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cognition	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within detection of temperature stimulus involved in sensory perception of pain	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in developmental process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within dopamine catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in dopamine metabolic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within dopamine metabolic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within dopamine metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within dopamine secretion	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within dopamine secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in estrogen metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within exploration behavior	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within fear response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in female pregnancy	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within glomerulus development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within glycogen metabolic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within habituation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within kidney development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within learning	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in learning	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within learning or memory	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within learning or memory	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mastication	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within memory	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in methylation	ISO Inferred from Sequence Orthology more info
involved_in methylation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within multicellular organism growth	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organismal response to stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of dopamine metabolic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of smooth muscle cell proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within norepinephrine metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within norepinephrine secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of homocysteine metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within prostaglandin metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein methylation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of blood pressure	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of blood pressure	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within renal albumin absorption	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within renal filtration	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within renal sodium excretion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within renin secretion into blood stream	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to amphetamine	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to angiotensin	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to corticosterone	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to cytokine	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to dopamine	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to external stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to food	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to hypoxia	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to methylphenidate	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to pain	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within response to salt	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to stress	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to temperature stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to toxic substance	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to wounding	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to xenobiotic stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in short-term memory	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within startle response	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within synaptic transmission, dopaminergic	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within visual learning	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info
located_in axon	ISO Inferred from Sequence Orthology more info
located_in cell body	ISO Inferred from Sequence Orthology more info
is_active_in cytosol	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IMP Inferred from Mutant Phenotype more info	PubMed
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in dendritic spine	ISO Inferred from Sequence Orthology more info
is_active_in glutamatergic synapse	ISO Inferred from Sequence Orthology more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	HDA more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
is_active_in postsynapse	ISO Inferred from Sequence Orthology more info
located_in postsynaptic membrane	ISO Inferred from Sequence Orthology more info
located_in synapse	IEA Inferred from Electronic Annotation more info
is_active_in vesicle	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: catechol O-methyltransferase

Names: catechol-O-methyltransferase 1

NP_001104532.1

EC 2.1.1.6

NP_001104533.1

EC 2.1.1.6

NP_031770.2

EC 2.1.1.6

XP_036015657.1

EC 2.1.1.6

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001111062.1 → NP_001104532.1 catechol O-methyltransferase

See identical proteins and their annotated locations for NP_001104532.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript. Variants 1-3 encode the same protein.

Source sequence(s)

AC133487, AK148311, AW908224, CX237493

Consensus CDS

CCDS28021.1

UniProtKB/Swiss-Prot

O88587, Q91XH4

Related

ENSMUSP00000000335.5, ENSMUST00000000335.12

Conserved Domains (1) summary

cl17173
Location:60 → 227

AdoMet_MTases; S-adenosylmethionine-dependent methyltransferases (SAM or AdoMet-MTase), class I; AdoMet-MTases are enzymes that use S-adenosyl-L-methionine (SAM or AdoMet) as a substrate for methyltransfer, creating the product S-adenosyl-L-homocysteine (AdoHcy). ...
NM_001111063.1 → NP_001104533.1 catechol O-methyltransferase

See identical proteins and their annotated locations for NP_001104533.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1. Variants 1-3 encode the same protein.

Source sequence(s)

AA250343, AC133487, AK148311, AW908224, GU324998

Consensus CDS

CCDS28021.1

UniProtKB/Swiss-Prot

O88587, Q91XH4

Related

ENSMUSP00000130077.2, ENSMUST00000165430.8

Conserved Domains (1) summary

cl17173
Location:60 → 227

AdoMet_MTases; S-adenosylmethionine-dependent methyltransferases (SAM or AdoMet-MTase), class I; AdoMet-MTases are enzymes that use S-adenosyl-L-methionine (SAM or AdoMet) as a substrate for methyltransfer, creating the product S-adenosyl-L-homocysteine (AdoHcy). ...
NM_007744.3 → NP_031770.2 catechol O-methyltransferase

See identical proteins and their annotated locations for NP_031770.2

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1-3 encode the same protein.

Source sequence(s)

AC133487, AK148311, AW908224, CX237493

Consensus CDS

CCDS28021.1

UniProtKB/Swiss-Prot

O88587, Q91XH4

Related

ENSMUSP00000111272.3, ENSMUST00000115609.10

Conserved Domains (1) summary

cl17173
Location:60 → 227

AdoMet_MTases; S-adenosylmethionine-dependent methyltransferases (SAM or AdoMet-MTase), class I; AdoMet-MTases are enzymes that use S-adenosyl-L-methionine (SAM or AdoMet) as a substrate for methyltransfer, creating the product S-adenosyl-L-homocysteine (AdoHcy). ...

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000082.7 Reference GRCm39 C57BL/6J

Range

18225632..18247006 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036159764.1 → XP_036015657.1 catechol O-methyltransferase isoform X1

Conserved Domains (1) summary

COG4122
Location:5 → 146

YrrM; Predicted O-methyltransferase YrrM [General function prediction only]