Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	1	271	22q11.21	COMT	catechol-O-methyltransferase
Mouse	1	265	16 11.4 cM	Comt	catechol-O-methyltransferase
Rat	1	264	11q23	Comt	catechol-O-methyltransferase

Previous and Unofficial Names

Comt1

Database Links
Alphafold	P21964 (Hs), O88587 (Mm), P22734 (Rn)
BRENDA	2.1.1.6
ChEMBL Target	CHEMBL2023 (Hs), CHEMBL3286068 (Mm), CHEMBL2372 (Rn)
DrugBank Target	P21964 (Hs)
Ensembl Gene	ENSG00000093010 (Hs), ENSMUSG00000000326 (Mm), ENSRNOG00000001889 (Rn)
Entrez Gene	1312 (Hs), 12846 (Mm), 24267 (Rn)
Human Protein Atlas	ENSG00000093010 (Hs)
KEGG Enzyme	2.1.1.6
KEGG Gene	hsa:1312 (Hs), mmu:12846 (Mm), rno:24267 (Rn)
OMIM	116790 (Hs)
Orphanet	ORPHA241992 (Hs)
Pharos	P21964 (Hs)
RefSeq Nucleotide	NM_001135161 (Hs), NM_007310 (Hs), NM_001135162 (Hs), NM_000754 (Hs), NM_007744 (Mm), NM_001111063 (Mm), NM_001111062 (Mm), NM_012531 (Rn)
RefSeq Protein	NP_009294 (Hs), NP_000745 (Hs), NP_001128633 (Hs), NP_001128634 (Hs), NP_001104533 (Mm), NP_031770 (Mm), NP_001104532 (Mm), NP_036663 (Rn)
UniProtKB	P21964 (Hs), O88587 (Mm), P22734 (Rn)
Wikipedia	COMT (Hs)

Enzyme Reaction
EC Number: 2.1.1.6 S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol Description Reaction Reference (-)-Noradrenaline -> normetanephrine (-)-Adrenaline -> metanephrine 3,4-Dihydroxymandelic acid -> vanillylmandelic acid Dopamine -> 3-methoxytyramine

Cofactors
Cofactor Species Comments Reference S-adenosyl methionine Human

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference tolcapone Hs Inhibition 9.5 – 9.6 pKi 3 ⤷ pKi 9.6 (Ki 2.7x10-10 M) soluble enzyme [3] Description: soluble enzyme pKi 9.5 (Ki 2.9x10-10 M) membrane-bound enzyme [3] Description: membrane-bound enzyme entacapone Hs Inhibition 8.7 – 9.5 pKi 3 ⤷ pKi 9.5 (Ki 3x10-10 M) soluble enzyme [3] Description: soluble enzyme pKi 8.7 (Ki 2x10-9 M) membrane-bound enzyme [3] Description: membrane-bound enzyme opicapone Hs Inhibition 9.0 pKi 2 ⤷ pKi 9.0 (Ki 1x10-9 M) [2] opicapone Mm Inhibition 8.8 pKi 2 ⤷ pKi 8.8 (Ki 1.5x10-9 M) [2] opicapone Rn Inhibition 8.8 pKi 2 ⤷ pKi 8.8 (Ki 1.5x10-9 M) [2]
View species-specific inhibitor tables

Clinically-Relevant Mutations and Pathophysiology
Disease:  Alcohol dependence Disease Ontology: DOID:0050741 OMIM: 103780
Disease:  DiGeorge syndrome Disease Ontology: DOID:11198 OMIM: 188400 Orphanet: ORPHA567
Disease:  Panic disorder 1; PAND1 Disease Ontology: DOID:594 OMIM: 167870
Disease:  Schizophrenia Disease Ontology: DOID:5419 OMIM: 181500 Orphanet: ORPHA3140
Disease:  Velocardiofacial syndrome Disease Ontology: DOID:12583 OMIM: 192430 Orphanet: ORPHA567

General Comments

SARS-CoV-2/COVID-19 Experimental in vitro evidence, using affinity-purification mass spectrometry (AP-MS), indicates a protein-protein interaction between COMT and the SARS-CoV-2 non-structural protein 7 (Nsp7) [1], although whether this interaction is realistic based on spatial distribution of the host and viral proteins within cells was not addressed in this study. Speculatively, COMT ligands such as entacapone could be utilised to examine the effect of inhibiting the COMT/Nsp7 protein-protein interaction on SARS-CoV-2 pathobiology.