COMT

Summary

COMT (catechol-O-methyltransferase, HGNC:2228) is a protein-coding gene on chromosome 22q11.21, encoding Catechol O-methyltransferase (P21964). Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones.

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.

Source: NCBI Gene 1312 — RefSeq curated summary.

At a glance

• Gene–disease (curated): paroxysmal dyskinesia (Moderate, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 154 total — 4 pathogenic
• Phenotypes (HPO): 131
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000754

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2228
Approved symbol	COMT
Name	catechol-O-methyltransferase
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000093010
Ensembl biotype	protein_coding
OMIM	116790
Entrez	1312

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 22 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000207636, ENST00000361682, ENST00000403184, ENST00000403710, ENST00000406520, ENST00000407537, ENST00000412786, ENST00000428707, ENST00000449653, ENST00000467943, ENST00000493893, ENST00000676678, ENST00000677397, ENST00000677470, ENST00000677564, ENST00000677675, ENST00000678240, ENST00000678255, ENST00000678769, ENST00000678868, ENST00000678945, ENST00000852828, ENST00000852829, ENST00000852830, ENST00000964893, ENST00000964894, ENST00000964895, ENST00000964896, ENST00000964897, ENST00000964898, ENST00000964899

RefSeq mRNA: 5 — MANE Select: NM_000754 NM_000754, NM_001135161, NM_001135162, NM_001362828, NM_007310

CCDS: CCDS13770, CCDS46663

Canonical transcript exons

ENST00000361682 — 6 exons

Exon	Start	End
ENSE00001056469	19961199	19961289
ENSE00001297813	19968536	19969975
ENSE00001316383	19964168	19964299
ENSE00001656924	19962527	19962815
ENSE00001871649	19941772	19941897
ENSE00003569391	19963566	19963759

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 98.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 78.9944 / max 544.4771, expressed in 1819 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191081	40.5983	1722
191084	11.8871	1668
191090	10.7661	830
191082	9.0914	1695
191091	2.5021	456
191083	1.7310	1158
191097	0.6662	390
191093	0.5784	345
191096	0.3538	166
191089	0.3131	172

Top tissues by expression

301 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	98.95	gold quality
right adrenal gland	UBERON:0001233	98.92	gold quality
stromal cell of endometrium	CL:0002255	98.90	gold quality
left adrenal gland	UBERON:0001234	98.83	gold quality
olfactory bulb	UBERON:0002264	98.82	gold quality
left adrenal gland cortex	UBERON:0035825	98.82	gold quality
adrenal cortex	UBERON:0001235	98.79	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.76	gold quality
spinal cord	UBERON:0002240	98.54	gold quality
pharyngeal mucosa	UBERON:0000355	98.43	gold quality
right lobe of liver	UBERON:0001114	98.40	gold quality
corpus callosum	UBERON:0002336	98.23	gold quality
esophagus mucosa	UBERON:0002469	98.14	gold quality
renal medulla	UBERON:0000362	98.10	gold quality
adrenal gland	UBERON:0002369	98.10	gold quality
left ovary	UBERON:0002119	98.07	gold quality
right ovary	UBERON:0002118	98.02	gold quality
right lung	UBERON:0002167	97.99	gold quality
body of tongue	UBERON:0011876	97.98	gold quality
nerve	UBERON:0001021	97.96	gold quality
tibial nerve	UBERON:0001323	97.96	gold quality
amygdala	UBERON:0001876	97.88	gold quality
ascending aorta	UBERON:0001496	97.87	gold quality
thoracic aorta	UBERON:0001515	97.87	gold quality
right coronary artery	UBERON:0001625	97.82	gold quality
tongue	UBERON:0001723	97.82	gold quality
ectocervix	UBERON:0012249	97.82	gold quality
endocervix	UBERON:0000458	97.78	gold quality
decidua	UBERON:0002450	97.78	gold quality
saliva-secreting gland	UBERON:0001044	97.72	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	128.19
E-HCAD-4	yes	68.70
E-HCAD-11	yes	33.10
E-HCAD-10	yes	22.73
E-MTAB-8410	yes	20.37
E-HCAD-13	yes	11.58
E-MTAB-10042	yes	9.25
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, ESR1, IKBKB, INS, KAT7, NFKB, PGR, RELA, TNF

miRNA regulators (miRDB)

52 targeting COMT, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628

Literature-anchored findings (GeneRIF, showing 40)

• A low-activity allele is associated with obsessive-compulsive bahavior in females, not in males as previously reported. (PMID:11840516)
• COMT activity may determine the individual response to levodopa and result in ethnic differences in Parkinson disease susceptibility. (PMID:11873938)
• possible association between the prophylactic efficacy of lithium in mood disorders and the following gene variants: catechol-O-methyltransferase (COMT) G158A, monoamine oxydase A (MAO-A) 30-bp repeat, G-protein beta 3-subunit (Gbeta3) C825T (PMID:11992559)
• possible influence of monoamine oxydase A (MAO-A), catechol-O-methyltransferase (COMT), serotonin receptor 2A (5-HT2A), dopamine receptor D2 (DRD2), and dopamine receptor D4 (DRD4) gene variants on timing of recurrence in mood disorders (PMID:11992560)
• Association between catechol-O-methyltransferase polymorphism and vitiligo. (PMID:12029502)
• polymorphism associated with schizophrenia in Chinese families in China (PMID:12082558)
• allelic variants of COMT gene may modulate the risk for schizophrenia (PMID:12090821)
• that self-reported schizotypy scores in both questionnaires were significantly related to COMT genotype (P = 0.028 for the PAS and P = 0.015 for the SPQ) with individuals homozygous for the high activity allele showing the highest scores. (PMID:12192614)
• Characterization of human soluble high and low activity allele-catalyzed catechol estrogen methylation. (PMID:12360102)
• A highly significant association between a COMT haplotype and schizophrenia (PMID:12402217)
• catalyzes the o-methylation inactivation pathway of the major metabolites of estrogen, 2- hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2). (PMID:12402217)
• Results suggested that liability to heroin-dependence was associated with -287 A/G polymorphism of COMT gene. (PMID:12476424)
• Contrary to expectations that COMT would be expressed predominantly in non-neuronal cells, the present study shows that neurons are the main cell populations expressing COMT mRNA in the prefrontal cortex and striatum. (PMID:12535946)
• Serum estradiol levels significantly correlate with COMT genotype. Differences in COMT genotype might be involved in causing variable effects of estrogens on diseases and on efficacy of hormone replacement therapy. (PMID:12571159)
• individuals homozygous for the met158 allele of the catechol-O-methyltransferase polymorphism (val158met) showed diminished regional mu-opioid system responses to pain compared with heterozygotes (PMID:12595695)
• There is an inherited difference in COMT polymorphism which is important in the pathogenesis of anxiety in women. (PMID:12605099)
• examination of gene polymorphism in postmenopausal cancer risk (PMID:12727796)
• the risk of having both low activity catechol-O-methyltransferase and high angiotensin-converting enzyme genotypes was over 10 times higher in schizophrenics with poor response to conventional neuroleptics (PMID:12729939)
• COMT polymorphism is of potential pharmacological importance to individual differences in the metabolism of catechol drugs and may be involved in the pathogenesis and treatment of fibromyalgia syndrome. (PMID:12739038)
• val/met variants in novelty seeking behavior (PMID:12740593)
• This study does not support the involvement of tyrosine hydroxylase, catechol-O-methyl transferase and Wolfram syndrome 1 polymorphisms in mood disorders. (PMID:12782971)
• Disease-related laminar difference of COMT expression may be involved in dysregulation of dopamine signaling circuits in the dorsolateral prefrontal cortex of patients with schizophrenia. (PMID:12799619)
• Methylation of multiple promoters of the COMT gene can selectively inactivate MB-COMT and may contribute to endometrial carcinogenesis. (PMID:12810635)
• Low COMT activity is associated with aggressive behavior in schizophrenia. (PMID:12815735)
• No significant association was found in Japanese patients between COMT polymorphism and schizophrenia. (PMID:12815736)
• There is an association between Val108/158 Met polymorphism of the COMT gene in schizophrenia. (PMID:12815739)
• There was a weak association with COMT genotype in neuroticism when the males and females were considered separately. There was no significant interaction between COMT and MAOA. (PMID:12815746)
• The functional polymorphism in the COMT gene may modify the phenotype of suicide attempts and anger-related traits. (PMID:12842306)
• The association of the frontal P300 amplitude with the G1947A COMT genotype further emphasizes the functional role of this single nucleotide polymorphism. (PMID:12842307)
• COMT gene polymorphism is not directly associated with obsessive-compulsive disorder (PMID:12900951)
• Data suggested that for the Han Chinese children with ADHD in the study, there was no association between ADHD and Val158Met polymorphism of COMT gene. (PMID:12903043)
• These findings indicate that COMT genotype is associated with several risk factors for breast cancer and suggest that the low-activity COMT*2 allele is associated with a reduced risk of breast cancer among premenopausal women. (PMID:14504192)
• COMT gene polymorphism significantly increased the risk of developing prostate carcinoma. (PMID:14508827)
• Catechol-O-methyltransferase (COMT( deficiency in mice increases the availability of L-DOPA, leading to enhanced dopaminergic tone, which may be associated with resistance to salt-induced hypertension. (PMID:14654758)
• Compared with the COMT Val/Val wildtype genotype, the adjusted odds ratio of endometrial cancer for women with the COMT Val/ (PMID:14656940)
• The catechol O-methyltransferase gene has been associated with cognitive and behavioral phenotypes in schizophrenia (PMID:14754787)
• The Met108 allozyme displayed a 70-90% decrease in immunoreactive protein when compared with WT, but there was no significant change in the level of immunoreactive protein for Thr52 (PMID:14966473)
• The Catechol-o-methyltransferase gene polymorphism is not associated with the generation and the severity of pregnancy induced hypertension. (PMID:14989982)
• There were no observed differences in the frequencies of allele and genotype between obsessive-compulsive disorder patients and control groups for COMT polymorphisms. (PMID:15005715)
• a role of the catechol-O-methyltransferase gene polymorphism in the pathogenesis of panic disorder in women (PMID:15009906)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	comta	ENSDARG00000015337
danio_rerio	comtb	ENSDARG00000025679
mus_musculus	Comt	ENSMUSG00000000326
rattus_norvegicus	Comt	ENSRNOG00000001889
caenorhabditis_elegans		WBGENE00012518
caenorhabditis_elegans		WBGENE00021487
caenorhabditis_elegans		WBGENE00021491
caenorhabditis_elegans		WBGENE00021492

Paralogs (2): COMTD1 (ENSG00000165644), TOMT (ENSG00000284844)

Protein

Protein identifiers

Catechol O-methyltransferase — P21964 (reviewed: P21964)

All UniProt accessions (8): P21964, A0A140VJG8, A0A7I2V370, A0A7I2V3G7, E7EMS6, E7EUU8, F8WBW9, H7BZ45

UniProt curated annotations — full annotation on UniProt →

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.

Subcellular location. Cytoplasm Cell membrane.

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

Post-translational modifications. The N-terminus is blocked.

Disease relevance. Schizophrenia (SCZD) [MIM:181500] A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Cofactor. Binds 1 Mg(2+) ion per subunit.

Polymorphism. Two major alleles, COMT1 or COMTH and COMT2 or COMTL are defined by a nucleotide G-to-A transition at codon 158, resulting in a valine-to-methionine substitution. Allele COMT*2 codes for protein variant p.Val158Met, a functional polymorphism resulting in 3- to 4-fold difference in catechol O-methyltransferase activity [MIM:621296]. Low enzyme activity alleles are associated with genetic susceptibility to alcoholism [MIM:103780].

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-dependent O-methyltransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P21964-1	Membrane-bound, MB-COMT	yes
P21964-2	Soluble, S-COMT

RefSeq proteins (5): NP_000745, NP_001128633, NP_001128634, NP_001349757, NP_009294 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002935	SAM_O-MeTrfase	Family
IPR017128	Catechol_O-MeTrfase_euk	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily

Pfam: PF01596

Enzyme classification (BRENDA):

• EC 2.1.1.6 — catechol O-methyltransferase (BRENDA: 26 organisms, 218 substrates, 355 inhibitors, 169 Km, 43 kcat entries)

Substrate kinetics (BRENDA)

36 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DOPAMINE	0.0005–48.071	31
S-ADENOSYL-L-METHIONINE	0.0031–3.9	24
NOREPINEPHRINE	0.0055–1.856	19
2-HYDROXYESTRADIOL	0.0001–0.0175	11
ADRENALINE	0.0014–0.48	9
CATECHOL	0.0084–0.833	7
EPINEPHRINE	0.009–0.3947	7
4-HYDROXYESTRADIOL	0.0004–0.0161	5
SALVIANOLIC ACID B	0.0113–0.0797	4
EPIGALLOCATECHIN GALLATE	0.0002–0.0048	3
ESCULETIN	0.0004–0.015	3
QUERCETIN	0.0015–0.0069	3
CATECHIN	0.0022–0.0089	2
EPICATECHIN	0.0043–0.0257	2
EPIGALLOCATECHIN	0.0081–0.0117	2

Catalyzed reactions (Rhea), 7 shown:

• a catechol + S-adenosyl-L-methionine = a guaiacol + S-adenosyl-L-homocysteine + H(+) (RHEA:17877)
• 2-hydroxy-17beta-estradiol + S-adenosyl-L-methionine = 2-methoxy-17beta-estradiol + S-adenosyl-L-homocysteine + H(+) (RHEA:53088)
• 2-hydroxy-17beta-estradiol + S-adenosyl-L-methionine = 2-hydroxy-3-methoxy-17beta-estradiol + S-adenosyl-L-homocysteine + H(+) (RHEA:53092)
• 4-hydroxy-17beta-estradiol + S-adenosyl-L-methionine = 4-methoxy-17beta-estradiol + S-adenosyl-L-homocysteine + H(+) (RHEA:53096)
• 2-hydroxyestrone + S-adenosyl-L-methionine = 2-methoxyestrone + S-adenosyl-L-homocysteine + H(+) (RHEA:53100)
• 4-hydroxyestrone + S-adenosyl-L-methionine = 4-methoxyestrone + S-adenosyl-L-homocysteine + H(+) (RHEA:53104)
• 2-hydroxyestrone + S-adenosyl-L-methionine = 2-hydroxy-3-methoxy-estrone + S-adenosyl-L-homocysteine + H(+) (RHEA:53108)

UniProt features (47 total): binding site 14, helix 13, strand 8, sequence variant 5, topological domain 2, chain 1, modified residue 1, splice variant 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
3BWY	X-RAY DIFFRACTION	1.3
6I3C	X-RAY DIFFRACTION	1.34
4PYI	X-RAY DIFFRACTION	1.35
6I3D	X-RAY DIFFRACTION	1.45
5LSA	X-RAY DIFFRACTION	1.5
4XUC	X-RAY DIFFRACTION	1.8
4PYJ	X-RAY DIFFRACTION	1.9
3BWM	X-RAY DIFFRACTION	1.98
4PYK	X-RAY DIFFRACTION	2.22
4XUE	X-RAY DIFFRACTION	2.3
4XUD	X-RAY DIFFRACTION	2.4
3A7E	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21964-F1	94.07	0.81

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (14): 169; 191; 191; 194; 219; 220; 220; 249; 92; 114; 122; 140 …

Post-translational modifications (1): 267

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-156581	Methylation
R-HSA-379397	Enzymatic degradation of dopamine by COMT
R-HSA-379398	Enzymatic degradation of Dopamine by monoamine oxidase
R-HSA-9679191	Potential therapeutics for SARS

MSigDB gene sets: 681 (showing top): GOBP_MEMORY, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, MODULE_93, GOBP_EXCRETION, GOBP_DIGESTION, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_COGNITION, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE_BY_CIRCULATORY_RENIN_ANGIOTENSIN, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE

GO Biological Process (54): behavioral fear response (GO:0001662), response to hypoxia (GO:0001666), synaptic transmission, dopaminergic (GO:0001963), startle response (GO:0001964), response to amphetamine (GO:0001975), renin secretion into blood stream (GO:0002001), glycogen metabolic process (GO:0005977), prostaglandin metabolic process (GO:0006693), response to oxidative stress (GO:0006979), memory (GO:0007613), visual learning (GO:0008542), response to xenobiotic stimulus (GO:0009410), response to wounding (GO:0009611), response to toxic substance (GO:0009636), gene expression (GO:0010467), dopamine secretion (GO:0014046), cellular response to phosphate starvation (GO:0016036), cerebellar cortex morphogenesis (GO:0021696), response to food (GO:0032094), methylation (GO:0032259), developmental process (GO:0032502), glomerulus development (GO:0032835), cholesterol efflux (GO:0033344), response to cytokine (GO:0034097), multicellular organism growth (GO:0035264), exploration behavior (GO:0035640), renal sodium excretion (GO:0035812), norepinephrine metabolic process (GO:0042415), dopamine metabolic process (GO:0042417), dopamine catabolic process (GO:0042420), catecholamine catabolic process (GO:0042424), habituation (GO:0046959), norepinephrine secretion (GO:0048243), detection of temperature stimulus involved in sensory perception of pain (GO:0050965), response to corticosterone (GO:0051412), artery development (GO:0060840), cellular response to cocaine (GO:0071314), mastication (GO:0071626), renal albumin absorption (GO:0097018), renal filtration (GO:0097205)

GO Molecular Function (7): magnesium ion binding (GO:0000287), methyltransferase activity (GO:0008168), O-methyltransferase activity (GO:0008171), catechol O-methyltransferase activity (GO:0016206), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (9): cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), axon (GO:0030424), dendrite (GO:0030425), synapse (GO:0045202), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), vesicle (GO:0031982)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Dopamine clearance from the synaptic cleft	2
Phase II - Conjugation of compounds	1
SARS-CoV Infections	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to stress	3
response to chemical	3
cellular anatomical structure	3
signal release	2
neuron projection	2
behavioral defense response	1
fear response	1
response to decreased oxygen levels	1
chemical synaptic transmission	1
response to external stimulus	1
neuromuscular process	1
response to amine	1
renal response to blood flow involved in circulatory renin-angiotensin regulation of systemic arterial blood pressure	1
protein secretion	1
energy reserve metabolic process	1
glucan metabolic process	1
prostanoid metabolic process	1
learning or memory	1
visual behavior	1
associative learning	1
macromolecule biosynthetic process	1
catecholamine secretion	1
cellular response to starvation	1
anatomical structure morphogenesis	1
cerebellum morphogenesis	1
cerebellar cortex development	1
response to nutrient levels	1
metabolic process	1
metal ion binding	1
transferase activity, transferring one-carbon groups	1
methyltransferase activity	1
O-methyltransferase activity	1
S-adenosylmethionine-dependent methyltransferase activity	1
binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
membrane	1
cell periphery	1
dendritic tree	1

Protein interactions and networks

STRING

2918 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COMT	MAOB	P27338	967
COMT	MAOA	P21397	964
COMT	DRD4	P21917	943
COMT	SLC6A4	P31645	943
COMT	DRD2	P14416	924
COMT	BDNF	P23560	920
COMT	SLC6A3	Q01959	917
COMT	ARVCF	O00192	895
COMT	PRODH	O43272	894
COMT	PRODH	O43272	890
COMT	OPRM1	P35372	871
COMT	HTR2A	P28223	865
COMT	ANKK1	Q8NFD2	853
COMT	CYP1A1	P04798	853
COMT	DTNBP1	Q96EV8	820

IntAct

234 interactions, top by confidence:

A	B	Type	Score
COMT	SLC7A1	psi-mi:“MI:0915”(physical association)	0.670
COMT	TMEM205	psi-mi:“MI:0915”(physical association)	0.670
TRIP13	COMT	psi-mi:“MI:0915”(physical association)	0.620
COMT	CNR2	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	COMT	psi-mi:“MI:0915”(physical association)	0.560
OTOP3	COMT	psi-mi:“MI:0915”(physical association)	0.560
COMT	GJB3	psi-mi:“MI:0915”(physical association)	0.560
SMIM1	COMT	psi-mi:“MI:0915”(physical association)	0.560
MYADML2	COMT	psi-mi:“MI:0915”(physical association)	0.560
COMT	GET1	psi-mi:“MI:0915”(physical association)	0.560
COMT	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
THSD7A	COMT	psi-mi:“MI:0915”(physical association)	0.560
COMT	TRHR	psi-mi:“MI:0915”(physical association)	0.560
NIPAL4	COMT	psi-mi:“MI:0915”(physical association)	0.560
COMT	PLPP6	psi-mi:“MI:0915”(physical association)	0.560
RHBDL1	COMT	psi-mi:“MI:0915”(physical association)	0.560
COMT	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
COMT	EMD	psi-mi:“MI:0915”(physical association)	0.560
COMT	SLC10A6	psi-mi:“MI:0915”(physical association)	0.560
COMT	TMEM14C	psi-mi:“MI:0915”(physical association)	0.560
COMT	MFSD14B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (210): COMT (Two-hybrid), KRTAP5-9 (Two-hybrid), KRT31 (Two-hybrid), TRIP13 (Two-hybrid), KRT40 (Two-hybrid), COMT (Affinity Capture-MS), TRIP13 (Two-hybrid), COL1A2 (Affinity Capture-MS), FGF2 (Affinity Capture-MS), EXO1 (Affinity Capture-MS), RIN1 (Affinity Capture-MS), USP6NL (Affinity Capture-MS), HIGD1A (Affinity Capture-MS), PPA2 (Affinity Capture-MS), COMT (Affinity Capture-MS)

ESM2 similar proteins: A0A1L1SUL6, F1LQY6, O35465, O43379, O75293, O88910, O88954, P0C0T1, P21964, P22339, P41214, P50747, Q13368, Q13572, Q14318, Q16342, Q1HAQ0, Q28955, Q2T9Z1, Q3B7U9, Q3TFD2, Q3TMX7, Q496Y0, Q4AC99, Q5BIM1, Q5E9A5, Q5R812, Q5RA63, Q5SZD4, Q64311, Q6DC64, Q6P5G6, Q6PFY8, Q80YV4, Q8BNV1, Q8BYN3, Q8NFZ0, Q8R1C6, Q8R1T1, Q8TCU6

Diamond homologs: A0A193KX02, A1Y9I9, A4IG53, A7MBI7, B6CZ46, B6CZ56, B6CZ62, F4ZGF2, G8T6H8, L0TAD5, O42898, O88587, P21964, P22734, P86243, Q00719, Q5H879, Q8NKC1, Q8WZ04, Q99028, B8NI24, O07431, Q9YDA1, A2BKH8, O26915, O27962, Q57636, Q86VU5, Q8TYL4, Q9ZTT5, A0A0S2UWA5, A0A0S2UWC9, A0A0S2UWT1, A0A2H5AIZ6, A0A397HK53, A0PVW4, A0QCH0, A1KI08, A1UKA3, A3Q3Q7

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
INS	“up-regulates quantity by expression”	COMT	“transcriptional regulation”
17beta-hydroxy-5alpha-androstan-3-one	up-regulates	COMT
RELA	“down-regulates quantity by repression”	COMT	“transcriptional regulation”
IKBKB	“down-regulates quantity by repression”	COMT	“transcriptional regulation”
entacapone	“down-regulates activity”	COMT	“chemical inhibition”
tolcapone	“down-regulates activity”	COMT	“chemical inhibition”
COMT	“down-regulates quantity”	dopamine	“chemical modification”
COMT	“up-regulates quantity”	3-methoxytyramine	“chemical modification”
TNF	“down-regulates quantity by repression”	COMT	“transcriptional regulation”
progesterone	down-regulates	COMT

Disease & clinical

Clinical variants and AI predictions

ClinVar

154 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	37
Likely benign	20
Benign	15

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1808679	GRCh37/hg19 22q11.21(chr22:19336598-21208828)x1	Pathogenic
2500149	NM_000754.4(COMT):c.575_576insT (p.Trp193fs)	Pathogenic
2574689	GRCh37/hg19 22q11.21(chr22:18916842-20311810)	Pathogenic
2684929	GRCh37/hg19 22q11.21(chr22:19533622-19938011)x3	Pathogenic

SpliceAI

1953 predictions. Top by Δscore:

Variant	Effect	Δscore
22:19962784:G:GT	donor_gain	1.0000
22:19962784:GGA:G	donor_gain	1.0000
22:19962785:GAG:G	donor_gain	1.0000
22:19962811:GAAAG:G	donor_gain	1.0000
22:19962812:AAAG:A	donor_loss	1.0000
22:19962813:AAG:A	donor_loss	1.0000
22:19962814:AG:A	donor_loss	1.0000
22:19962815:GGT:G	donor_loss	1.0000
22:19962817:T:A	donor_loss	1.0000
22:19963554:A:AG	acceptor_gain	1.0000
22:19963555:A:AG	acceptor_gain	1.0000
22:19963556:C:G	acceptor_gain	1.0000
22:19963559:T:TA	acceptor_gain	1.0000
22:19963561:CACA:C	acceptor_loss	1.0000
22:19963562:A:AG	acceptor_gain	1.0000
22:19963562:ACAG:A	acceptor_gain	1.0000
22:19963563:C:G	acceptor_gain	1.0000
22:19963564:A:AG	acceptor_gain	1.0000
22:19963565:G:GG	acceptor_gain	1.0000
22:19963565:GGC:G	acceptor_gain	1.0000
22:19963565:GGCA:G	acceptor_gain	1.0000
22:19963565:GGCAA:G	acceptor_gain	1.0000
22:19963755:ACAAG:A	donor_loss	1.0000
22:19963756:CAAGG:C	donor_loss	1.0000
22:19963757:AAGGT:A	donor_loss	1.0000
22:19963758:AGGT:A	donor_loss	1.0000
22:19963759:GG:G	donor_loss	1.0000
22:19963760:G:GA	donor_loss	1.0000
22:19963760:G:GG	donor_gain	1.0000
22:19964162:TTCCA:T	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000051672 (22:19940730 C>G,T), RS1000084751 (22:19940073 C>G), RS1000125169 (22:19951062 G>A), RS1000196723 (22:19951282 C>T), RS1000255869 (22:19951539 G>A,C), RS1000373379 (22:19966222 G>A), RS1000507628 (22:19946550 C>T), RS1000527710 (22:19944627 A>T), RS1000641500 (22:19950635 G>A), RS1000806506 (22:19954983 G>A), RS1000834327 (22:19955955 T>C), RS1000874926 (22:19961430 T>C,G), RS1000892565 (22:19957222 T>C), RS1000944606 (22:19957100 G>A,T), RS1001106907 (22:19952136 C>CA)

Disease associations

OMIM: gene MIM:116790 | disease phenotypes: MIM:617825, MIM:181500, MIM:192600, MIM:209900, MIM:608363, MIM:167870

GenCC curated gene-disease

Disease	Classification	Inheritance
paroxysmal dyskinesia	Moderate	Autosomal dominant

Mondo (10): dilated cardiomyopathy (MONDO:0005021), glucocorticoid deficiency 5 (MONDO:0040502), schizophrenia (MONDO:0005090), 22q11.2 deletion syndrome (MONDO:0018923), schizophrenia, susceptibility to (MONDO:0100182), familial hypertrophic cardiomyopathy (MONDO:0024573), Bardet-Biedl syndrome (MONDO:0015229), chromosome 22q11.2 microduplication syndrome (MONDO:0012020), panic disorder 1 (MONDO:0008187), paroxysmal dyskinesia (MONDO:0015427)

Orphanet (7): Dilated cardiomyopathy (Orphanet:217604), 22q11.2 deletion syndrome (Orphanet:567), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Bardet-Biedl syndrome (Orphanet:110), 22q11.2 duplication syndrome (Orphanet:1727), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

131 total (30 of 131 shown, HPO-id order):

HPO	Term
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000076	Vesicoureteral reflux
HP:0000089	Renal hypoplasia
HP:0000113	Polycystic kidney dysplasia
HP:0000130	Abnormality of the uterus
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000262	Turricephaly
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000385	Small earlobe
HP:0000389	Chronic otitis media
HP:0000396	Overfolded helix
HP:0000405	Conductive hearing impairment
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000453	Choanal atresia

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST006249_108	Serum metabolite levels	1.000000e-48
GCST006249_67	Serum metabolite levels	6.000000e-11
GCST006434_1	Systolic blood pressure x alcohol consumption interaction (2df test)	3.000000e-08
GCST009733_204	Urinary metabolite levels in chronic kidney disease	2.000000e-59
GCST009733_226	Urinary metabolite levels in chronic kidney disease	2.000000e-11
GCST009733_227	Urinary metabolite levels in chronic kidney disease	2.000000e-28
GCST009735_20	Urinary metabolite modules (eigenmetabolites) in chronic kidney disease	5.000000e-54

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004329	alcohol drinking
EFO:0006335	systolic blood pressure
EFO:0005116	urinary metabolite measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
C567224	Chromosome 22q11.2 Microduplication Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2023 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 31,258 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1089318	OPICAPONE	4	648
CHEMBL1324	TOLCAPONE	4	13,819
CHEMBL953	ENTACAPONE	4	16,791

PharmGKB: 1 entry (VIP=true, CPIC=true)

PharmGKB clinical annotations

68 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs13306278	Efficacy	3	Selective serotonin reuptake inhibitors	Major Depressive Disorder
rs165599	Efficacy	3	risperidone	Schizophrenia
rs165599	Efficacy	3	bupropion	Tobacco Use Disorder
rs4633	Other	3	opioids	Pain
rs4633	Toxicity	3	opioids	Dizziness
rs4633	Toxicity	3	opioids	Physiological sexual disorder
rs4633	Efficacy	3	butorphanol
rs4633	Efficacy	4	risperidone	Schizophrenia
rs4646316	Toxicity	3	cisplatin	Drug Toxicity;Neoplasms;Ototoxicity
rs4646316	Toxicity	3	cisplatin	Neoplasms;Nephrotoxicity
rs4680	Toxicity	3	antipsychotics	Tardive Dyskinesia
rs4680	Other	3	opioids	Pain
rs4680	Efficacy	3	venlafaxine	Anxiety Disorders;Depressive Disorder
rs4680	Other	3	Analgesics;Antiinflammatory agents;non-steroids;Ergot alkaloids;opioids;sumatriptan
rs4680	Toxicity	3	nicotine	Tobacco Use Disorder
rs4680	Efficacy	3	modafinil	Methamphetamine dependence
rs4680	Toxicity	3	opioids	Hyperalgesia
rs4680	Toxicity	3	opioids	Death;Opioid-Related Disorders
rs4680	Toxicity	3	methadone	Neonatal Abstinence Syndrome
rs4680	Efficacy	3	nicotine	Tobacco Use Disorder
rs4680	Other	3	antipsychotics	Schizophrenia
rs4680	Toxicity	3	buprenorphine;fentanyl;tramadol	Exanthema;Opioid-Related Disorders
rs4680	Toxicity	3	buprenorphine	Neonatal Abstinence Syndrome
rs4680	Efficacy	3	fentanyl	Pain
rs4680	Toxicity	3	fentanyl	Somnolence
rs4680	Dosage	3	morphine	Pain;Pain;Postoperative
rs4680	Efficacy	3	remifentanil	Pain
rs4680	Efficacy	3	opioids	Pain
rs4680	Efficacy	3	oxycodone
rs4680	Efficacy	3	fluvoxamine	Major Depressive Disorder
rs4680	Dosage	3	opioids	Pain;Pain;Postoperative
rs4680	Efficacy	3	propranolol	Temporomandibular joint dysfunction syndrome
rs4680	Efficacy	3	morphine	Pain
rs4680	Dosage	3	sufentanil
rs4680	Toxicity	3	naloxone;oxycodone	Vomiting
rs4680	Toxicity	3	naloxone;oxycodone	Erythema
rs4680	Toxicity	3	buprenorphine;fentanyl;tramadol	adverse events;Opioid-Related Disorders

PharmGKB variants

28 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4633	COMT	3	2.00	5	butorphanol;risperidone;opioids
rs4680	COMT	3	5.00	43	antipsychotics;buprenorphine;methadone;buprenorphine;fentanyl;tramadol;fentanyl;remifentanil;sufentanil;oxycodone;opioids;morphine
rs4818	COMT	3	3.00	3	risperidone;opioids;quetiapine
rs6267	COMT		0.00	0
rs6269	COMT	3	3.00	5	morphine;butorphanol;opioids;quetiapine
rs165599	ARVCF, COMT	3	2.75	2	risperidone;bupropion
rs165728	ARVCF, COMT		0.00	0
rs174699	ARVCF, COMT		0.00	0
rs737865	COMT, TXNRD2		0.00	0
rs737866	COMT, TXNRD2		0.00	0
rs740603	COMT	3	0.00	2	buprenorphine;methadone
rs933271	COMT, TXNRD2	3	2.50	1	methadone
rs2020917	COMT, TXNRD2		0.00	0
rs2075507	COMT, TXNRD2		0.00	0
rs2239393	COMT		0.00	0
rs4646312	COMT		0.00	0
rs4646316	COMT	3	2.25	2	cisplatin
rs5746849	COMT		0.00	0
rs7287550	COMT, TXNRD2		0.00	0
rs9332377	ARVCF, COMT	3	2.75	2	cisplatin
rs9606186	COMT, TXNRD2	3	2.25	1	risperidone
rs13306278	COMT, TXNRD2	3	2.50	1	Selective serotonin reuptake inhibitors
rs5993883	COMT	3	3.00	1	quetiapine
rs165774	COMT		0.00	0
rs174696	COMT		0.00	0
rs5993882	COMT		0.00	0
rs165722	COMT		0.00	0
rs174675	COMT		0.00	0

PharmGKB dosing guidelines

3 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	alfentanil;buprenorphine;codeine;fentanyl;hydrocodone;hydromorphone;levomethadone;morphine;naltrexone;remifentanil;sufentanil;tramadol	Annotation of CPIC Guideline for alfentanil, buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, levomethadone, morphine, naltrexone, remifentanil, sufentanil, tramadol and COMT, OPRM1
CPIC	methadone;oxycodone	Annotation of CPIC Guideline for methadone, oxycodone and COMT, CYP2D6, OPRM1
DPWG	methylphenidate	Annotation of DPWG Guideline for methylphenidate and COMT

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Catecholamine turnover

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
tolcapone	Inhibition	9.54	pKi
opicapone	Inhibition	9.0	pKi
entacapone	Inhibition	8.7	pKi

Binding affinities (BindingDB)

5 measured of 5 human assays (5 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-hydroxy-2-[3-(4-methoxyphenoxy)phenyl]-3-methylpyrimidin-4-one	IC50	93 nM	US-9260413: Inhibitors of catechol O-methyl transferase and their use in the treatment of psychotic disorders
5-hydroxy-3-methyl-2-(3-phenylphenyl)pyrimidin-4-one	IC50	170 nM	US-9260413: Inhibitors of catechol O-methyl transferase and their use in the treatment of psychotic disorders
2-[4-chloro-3-(trifluoromethyl)phenyl]-5-hydroxy-3-methylpyrimidin-4-one	IC50	180 nM	US-9260413: Inhibitors of catechol O-methyl transferase and their use in the treatment of psychotic disorders
5-hydroxy-2-[4-(trifluoromethyl)phenyl]-1,3-diazinan-4-one	IC50	210 nM	US-9260413: Inhibitors of catechol O-methyl transferase and their use in the treatment of psychotic disorders
5-hydroxy-2-[3-(2-phenylethynyl)phenyl]-1,3-diazinan-4-one	IC50	590 nM	US-9260413: Inhibitors of catechol O-methyl transferase and their use in the treatment of psychotic disorders

ChEMBL bioactivities

169 potent at pChembl≥5 of 198 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Ki	1	nM	OPICAPONE
8.96	Ki	1.1	nM	CHEMBL1091204
8.89	Ki	1.3	nM	CHEMBL1089630
8.80	Ki	1.6	nM	CHEMBL1091983
8.70	IC50	1.995	nM	CHEMBL4174978
8.70	IC50	1.995	nM	CHEMBL4167128
8.66	Ki	2.2	nM	CHEMBL1089504
8.50	IC50	3.162	nM	CHEMBL4170443
8.40	IC50	3.981	nM	CHEMBL4171117
8.40	IC50	3.981	nM	CHEMBL4172614
8.22	Ki	6	nM	CHEMBL1091982
8.20	IC50	6.31	nM	CHEMBL4169861
8.20	IC50	6.31	nM	CHEMBL4177089
8.20	IC50	6.3	nM	CHEMBL4462175
8.10	IC50	7.943	nM	CHEMBL4160303
8.04	Ki	9.2	nM	CHEMBL1089505
8.00	Ki	10	nM	OPICAPONE
8.00	IC50	10	nM	CHEMBL4163421
8.00	IC50	10	nM	CHEMBL4461693
8.00	IC50	10	nM	CHEMBL4470211
7.99	Ki	10.2	nM	CHEMBL1089536
7.97	Ki	10.6	nM	CHEMBL1089539
7.89	IC50	13	nM	CHEMBL4458006
7.80	IC50	16	nM	CHEMBL4531460
7.78	Ki	16.6	nM	CHEMBL1091981
7.77	Ki	17	nM	CHEMBL1089538
7.77	Ki	17	nM	CHEMBL1089537
7.70	IC50	19.95	nM	CHEMBL4174102
7.70	IC50	19.95	nM	CHEMBL4176008
7.70	IC50	19.95	nM	CHEMBL4174117
7.62	IC50	24	nM	CHEMBL4563060
7.48	IC50	33	nM	CHEMBL4464343
7.46	IC50	35	nM	CHEMBL3798524
7.42	IC50	38	nM	CHEMBL4449462
7.40	IC50	40	nM	CHEMBL3799913
7.40	IC50	40	nM	CHEMBL4453736
7.40	IC50	40	nM	CHEMBL4583818
7.40	IC50	40	nM	CHEMBL4447751
7.33	IC50	47	nM	CHEMBL3425734
7.30	IC50	49.5	nM	CHEMBL3799623
7.30	IC50	50.12	nM	CHEMBL4162990
7.30	IC50	50	nM	CHEMBL4476127
7.30	IC50	50	nM	CHEMBL4523002
7.28	IC50	53	nM	CHEMBL3425735
7.27	IC50	54	nM	CHEMBL3818719
7.26	IC50	55	nM	CHEMBL3800198
7.24	IC50	57	nM	CHEMBL3425740
7.22	IC50	60	nM	CHEMBL4556206
7.22	IC50	60	nM	ENTACAPONE
7.21	IC50	61	nM	CHEMBL3425738

PubChem BioAssay actives

106 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Opicapone	1153918: Inhibition of catalytic activity of human cloned COMT expressed in Escherichia coli using [3H]-S-adenosylmethionine as substrate after 20 mins by liquid scintillation counting	ki	0.0010	uM
3-chloro-5,6-dihydroxy-7-nitro-1-benzothiophene-2-carboxylic acid	474552: Inhibition of human recombinant COMT by microplate screening assay	ki	0.0010	uM
5-cyclopentylsulfonyl-7-fluoroquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.0020	uM
5-(2-benzylpyrrolidin-1-yl)sulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.0020	uM
5-[3-(4-fluorophenyl)pyrrolidin-1-yl]sulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.0032	uM
7-fluoro-5-(4-fluorophenyl)sulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.0040	uM
7-fluoro-5-pyrrolidin-1-ylsulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.0040	uM
5-cyclopentylsulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.0063	uM
7-fluoro-5-(4-methylphenyl)sulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.0063	uM
2-[(2,6-dimethylphenyl)methyl]-7-hydroxy-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.0063	uM
5-pyrrolidin-1-ylsulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.0079	uM
7-chloro-5-pyrrolidin-1-ylsulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.0100	uM
2-[(2,4-dichlorophenyl)methyl]-7-hydroxy-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.0100	uM
2-[(2,6-dichlorophenyl)methyl]-7-hydroxy-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.0100	uM
2-[(2,4-dimethylphenyl)methyl]-7-hydroxy-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.0130	uM
2-[(2-chloro-6-fluorophenyl)methyl]-7-hydroxy-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.0160	uM
7-chloro-5-cyclopentylsulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.0199	uM
7-methyl-5-pyrrolidin-1-ylsulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.0199	uM
2-[(2,6-difluorophenyl)methyl]-7-hydroxy-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.0380	uM
2-[(2-chlorophenyl)methyl]-7-hydroxy-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.0400	uM
2-[(2-chloro-4-fluorophenyl)methyl]-7-hydroxy-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.0400	uM
2-[(2,3-dimethylphenyl)methyl]-7-hydroxy-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.0400	uM
1-[4-(1-benzylpyrazol-4-yl)-2-pyridinyl]-3-hydroxypyridin-4-one	1298723: Inhibition of recombinant human C-terminal His6-tagged MB-COMT expressed in Bacmid using SAM/dopamine as substrate preincubated for 2 hrs followed by substrate addition measured after 25 mins by SAC TAMRA tracer-based fluorescence polarization assay	ic50	0.0495	uM
7-hydroxy-2-[(2-methylphenyl)methyl]-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.0500	uM
2-[(2-fluorophenyl)methyl]-7-hydroxy-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.0500	uM
5-ethylsulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.0501	uM
2-N,2-N,3-N,3-N-tetraethyl-6,7-dihydroxy-5-nitronaphthalene-2,3-dicarboxamide	1308078: Inhibition of human recombinant His-tagged soluble COMT expressed in Escherichia coli BL21 using aesculetin as substrate after 60 mins by microplate assay in presence of SAM	ic50	0.0540	uM
5-hydroxy-2-(1-hydroxybutyl)-1-(3-phenylphenyl)pyridin-4-one	1205874: Inhibition of C-terminal His6-tagged recombinant human membrane bound COMT expressed in Bacmid infected Sf-9 insect cells using dopamine/SAM as substrate/cofactor preincubated for 2 hrs followed by dopamine/SAM addition after 25 mins by fluorescence polarization assay	ic50	0.0570	uM
7-hydroxy-2-[[2-(trifluoromethyl)phenyl]methyl]-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.0600	uM
2-[(2,5-dimethylphenyl)methyl]-7-hydroxy-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.0630	uM
5-[4-(trifluoromethyl)phenyl]sulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.0631	uM
(E)-1-(3,4-dihydroxy-5-nitrophenyl)-3-(3-methoxyphenyl)prop-2-en-1-one	1659946: Inhibition of COMT (unknown origin)	ic50	0.0700	uM
5-[5-[1-(4-methoxyphenyl)cyclopropyl]-1H-pyrazol-3-yl]-2,4-dimethyl-1,3-thiazole	1679183: Inhibition of recombinant wild-type human COMT expressed in Escherichia coli BL21 using 4-nitrocatechol-Alexa488 as substrate in presence of cofactor SAM preincubated for 1 min followed by substrate addition and measured every 60 sec up to 180 times by fluorescence based microtiter plate reader analysis	ic50	0.0750	uM
7-fluoro-5-[4-(trifluoromethyl)phenyl]sulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.0794	uM
5-hydroxy-2-[hydroxy(phenyl)methyl]-1-(3-phenylphenyl)pyridin-4-one	1205874: Inhibition of C-terminal His6-tagged recombinant human membrane bound COMT expressed in Bacmid infected Sf-9 insect cells using dopamine/SAM as substrate/cofactor preincubated for 2 hrs followed by dopamine/SAM addition after 25 mins by fluorescence polarization assay	ic50	0.0880	uM
2-[(7-hydroxy-8-oxo-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-2-yl)methyl]benzonitrile	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.1000	uM
5-hydroxy-2-(hydroxymethyl)-1-(4-phenylphenyl)pyridin-4-one	1205874: Inhibition of C-terminal His6-tagged recombinant human membrane bound COMT expressed in Bacmid infected Sf-9 insect cells using dopamine/SAM as substrate/cofactor preincubated for 2 hrs followed by dopamine/SAM addition after 25 mins by fluorescence polarization assay	ic50	0.1400	uM
5-hydroxy-2-(hydroxymethyl)-1-(3-phenylphenyl)pyridin-4-one	1205874: Inhibition of C-terminal His6-tagged recombinant human membrane bound COMT expressed in Bacmid infected Sf-9 insect cells using dopamine/SAM as substrate/cofactor preincubated for 2 hrs followed by dopamine/SAM addition after 25 mins by fluorescence polarization assay	ic50	0.1400	uM
1-(4-butylphenyl)-5-hydroxy-2-(hydroxymethyl)pyridin-4-one	1205874: Inhibition of C-terminal His6-tagged recombinant human membrane bound COMT expressed in Bacmid infected Sf-9 insect cells using dopamine/SAM as substrate/cofactor preincubated for 2 hrs followed by dopamine/SAM addition after 25 mins by fluorescence polarization assay	ic50	0.1600	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148113: Binding affinity to human COMT incubated for 45 mins by Kinobead based pull down assay	kd	0.1693	uM
(5E)-5-[(3,4-dihydroxy-5-nitrophenyl)methylidene]-3-ethyl-1,3-thiazolidine-2,4-dione	1308078: Inhibition of human recombinant His-tagged soluble COMT expressed in Escherichia coli BL21 using aesculetin as substrate after 60 mins by microplate assay in presence of SAM	ic50	0.1790	uM
5-hydroxy-2-(1-hydroxy-2-methylpropyl)-1-(3-phenylphenyl)pyridin-4-one	1205874: Inhibition of C-terminal His6-tagged recombinant human membrane bound COMT expressed in Bacmid infected Sf-9 insect cells using dopamine/SAM as substrate/cofactor preincubated for 2 hrs followed by dopamine/SAM addition after 25 mins by fluorescence polarization assay	ic50	0.1800	uM
7-chloro-5-(4-fluorophenyl)sulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.1995	uM
2,4-dimethyl-5-[5-(1-phenylcyclopropyl)-1H-pyrazol-3-yl]-1,3-thiazole	1679183: Inhibition of recombinant wild-type human COMT expressed in Escherichia coli BL21 using 4-nitrocatechol-Alexa488 as substrate in presence of cofactor SAM preincubated for 1 min followed by substrate addition and measured every 60 sec up to 180 times by fluorescence based microtiter plate reader analysis	ic50	0.2100	uM
2-benzyl-7-hydroxy-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.2200	uM
7-hydroxy-2-[(2-methoxyphenyl)methyl]-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-8-one	1611900: Inhibition of human MB-COMT expressed in HEK293 cells using dopamine as substrate and SAM as cofactor preincubated for 30 mins followed by substrate addition and measured after 40 mins by HTRF assay	ic50	0.2500	uM
5-(4-methylphenyl)quinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.2512	uM
(E)-3-(3-bromophenyl)-1-(3,4-dihydroxy-5-nitrophenyl)prop-2-en-1-one	1659946: Inhibition of COMT (unknown origin)	ic50	0.2900	uM
7-chloro-5-(4-methylphenyl)sulfonylquinolin-8-ol	1363208: Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay	ic50	0.3162	uM
9-hydroxy-6H-pyrido[2,1-c][1,4]benzothiazin-8-one	1205874: Inhibition of C-terminal His6-tagged recombinant human membrane bound COMT expressed in Bacmid infected Sf-9 insect cells using dopamine/SAM as substrate/cofactor preincubated for 2 hrs followed by dopamine/SAM addition after 25 mins by fluorescence polarization assay	ic50	0.4000	uM

CTD chemical–gene interactions

160 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tolcapone	decreases activity, increases abundance, decreases abundance, decreases reaction, increases methylation	15
Levodopa	decreases activity, increases abundance, affects response to substance, increases methylation, decreases reaction	11
Estradiol	affects cotreatment, increases abundance, decreases activity, decreases abundance, decreases reaction (+4 more)	8
bisphenol A	decreases expression, increases expression, increases methylation, decreases reaction	5
Dopamine	decreases activity, increases abundance, decreases reaction, increases methylation	5
Fulvestrant	decreases expression, decreases reaction, increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	4
entacapone	increases abundance, decreases reaction, increases methylation, decreases activity	3
Estrogens	affects metabolic processing, decreases expression	3
Hydrogen Peroxide	decreases expression, increases expression	3
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	3
Genistein	decreases expression, decreases reaction, increases methylation, affects binding, increases reaction (+1 more)	3
2-hydroxyestradiol	affects metabolic processing, increases methylation	2
daidzein	decreases reaction, increases methylation, decreases activity, decreases expression	2
4-hydroxyestradiol	affects metabolic processing, increases methylation, decreases reaction	2
cobaltous chloride	decreases expression	2
catechol	affects cotreatment, decreases reaction, increases expression, increases abundance, increases response to substance (+1 more)	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
Estrogens, Catechol	decreases metabolic processing, decreases activity, increases methylation	2
Epinephrine	increases methylation, decreases activity, increases abundance	2
Mercury	affects response to substance	2
Methamphetamine	affects response to substance, increases response to substance	2
Methyldopa	increases methylation, decreases activity	2
Norepinephrine	increases methylation, decreases activity, increases abundance	2
Smoke	decreases expression	2
3,4-Dihydroxyphenylacetic Acid	increases methylation, decreases activity, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
perfluorodecanesulfonic acid	increases expression	1

ChEMBL screening assays

55 unique, capped per target: 47 binding, 8 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1007121	Binding	Inhibition of catechol-O-methyl transferase at 10 uM	Discovery of benzoylpiperazines as a novel class of potent and selective GlyT1 inhibitors. — Bioorg Med Chem Lett
CHEMBL3541531	ADMET	Drug metabolism in human liver cytosol assessed as COMT-mediated methylation after 10 to 30 mins by HPLC analysis in presence of SAM	Comparison of metabolism of sesamin and episesamin by drug-metabolizing enzymes in human liver. — Drug Metab Dispos

Cellosaurus cell lines

4 cell lines: 2 cancer cell line, 1 transformed cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2UW	Abcam HEK293T COMT KO	Transformed cell line	Female
CVCL_E7ND	KOLF2.1J COMT 21.8kbdel DEL/DEL	Induced pluripotent stem cell	Male
CVCL_SJ49	HAP1 COMT (-) 1	Cancer cell line	Male
CVCL_SJ50	HAP1 COMT (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

159 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00629018	PHASE2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	PHASE2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy
NCT00765518	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
NCT00847964	PHASE2	COMPLETED	Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery
NCT01020968	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy
NCT01302171	PHASE2	COMPLETED	Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy
NCT01350310	PHASE2	COMPLETED	Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy
NCT02133911	PHASE2	COMPLETED	A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy
NCT03071653	PHASE2	SUSPENDED	Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
NCT03572660	PHASE2	ACTIVE_NOT_RECRUITING	Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM
NCT03775070	PHASE2	COMPLETED	Simvastatin Therapy in Patients With Dilated Cardiomyopathy.
NCT04405804	PHASE2	UNKNOWN	Early Administration of Ivabradine in Children With Heart Failure
NCT05410873	PHASE2	COMPLETED	Examining the Effects of Mitochondrial Oxidative Stress in DCM
NCT06632834	PHASE2	RECRUITING	Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation
NCT00585546	PHASE1	TERMINATED	Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure
NCT02293603	PHASE1	UNKNOWN	Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC)
NCT03062956	PHASE1	COMPLETED	A Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491
NCT03129568	PHASE1	COMPLETED	Transcoronary Infusion of Cardiac Progenitor Cells in Pediatric Dilated Cardiomyopathy
NCT04982081	PHASE1	UNKNOWN	Treating Congestive HF With hiPSC-CMs Through Endocardial Injection
NCT06381466	PHASE1	TERMINATED	A Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral AZD0233 Compared With Placebo in Healthy Adult Participants.
NCT06464588	PHASE1	RECRUITING	A Phase 1 Open-Label Study of the Safety of Intravenous Allogeneic Neonatal Mesenchymal Cells (nMSCs) in Young Adult (1A) and Pediatric (1B) Patients With Dilated Cardiomyopathy (DCM)
NCT06902896	PHASE1	COMPLETED	Safety and Efficacy of FAP iCDC in End-stage Dilated Cardiomyopathy
NCT07137338	PHASE1	RECRUITING	A Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy
NCT07241104	PHASE1	RECRUITING	A Study of AZD4063 in PLN R14del Dilated Cardiomyopathy