COMT

catechol-O-methyltransferase, the group of MicroRNA protein coding host genes|7BS small molecule methyltransferases

Basic information

Region (hg38): 22:19941371-19969975

Links

ENSG00000093010 ∙ NCBI:1312 ∙ OMIM:116790 ∙ HGNC:2228 ∙ Uniprot:P21964 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• paroxysmal dyskinesia (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Medication response, association with	AD	Pharmacogenomic	Variants may involve clinically relevant drug metabolism	General	12716966; 15927391; 16876132; 17522626; 17644310; 18214865; 19462300; 19858760; 20053459; 20071037; 20216107; 20591499; 20877297; 21280081; 21788083; 22417933; 22483292

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COMT gene.

• Bardet-Biedl syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COMT gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				7	7	14
missense			5	1	2	8
nonsense						0
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding			25	24	9	58
Total	1	0	30	32	18

Variants in COMT

This is a list of pathogenic ClinVar variants found in the COMT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-19941423-G-A			Likely benign (Jun 14, 2018)
22-19941504-C-T			Benign (Jun 14, 2018)
22-19941618-T-TG			Benign (Jun 14, 2018)
22-19941682-C-T		not specified • Primary dilated cardiomyopathy	Benign/Likely benign (Jan 25, 2024)
22-19941683-G-GC		not specified • Primary dilated cardiomyopathy	Benign/Likely benign (Sep 13, 2023)
22-19941684-C-A		Primary dilated cardiomyopathy	Likely benign (Sep 21, 2023)
22-19941687-C-T		Primary dilated cardiomyopathy	Likely benign (Jan 14, 2023)
22-19941688-G-A		Primary dilated cardiomyopathy	Likely benign (Dec 25, 2023)
22-19941688-G-C		Primary dilated cardiomyopathy	Likely benign (Jun 16, 2022)
22-19941701-C-G		Primary dilated cardiomyopathy	Uncertain significance (Aug 31, 2022)
22-19941702-T-G		Tramadol response	drug response (Apr 28, 2018)
22-19941702-T-TGCTGCGCCCCGC		Primary dilated cardiomyopathy • Cardiovascular phenotype	Uncertain significance (Aug 11, 2023)
22-19941704-C-T		Tramadol response	drug response (Apr 28, 2018)
22-19941705-TGCGCCCCGCGCC-T		Primary dilated cardiomyopathy • Cardiovascular phenotype	Uncertain significance (Aug 06, 2024)
22-19941705-T-TGCGCCCCGCGCC		Primary dilated cardiomyopathy • Cardiovascular phenotype	Uncertain significance (May 22, 2023)
22-19941708-G-A		Primary dilated cardiomyopathy • Cardiovascular phenotype	Likely benign (Dec 29, 2023)
22-19941712-C-G		Primary dilated cardiomyopathy	Uncertain significance (Jun 07, 2022)
22-19941714-C-T		Cardiovascular phenotype	Likely benign (Dec 23, 2022)
22-19941716-C-A		Primary dilated cardiomyopathy • Cardiovascular phenotype	Uncertain significance (Apr 20, 2024)
22-19941720-G-A		Primary dilated cardiomyopathy	Likely benign (Mar 29, 2022)
22-19941721-C-A		Cardiovascular phenotype • Primary dilated cardiomyopathy	Uncertain significance (Apr 22, 2023)
22-19941720-G-GCCCCGCA		Primary dilated cardiomyopathy • Cardiovascular phenotype	Uncertain significance (Mar 13, 2022)
22-19941727-A-C		Primary dilated cardiomyopathy • Cardiovascular phenotype • Glucocorticoid deficiency 5	Uncertain significance (Jul 05, 2024)
22-19941727-A-G		Primary dilated cardiomyopathy • Cardiovascular phenotype	Uncertain significance (Aug 22, 2022)
22-19941727-A-ACCCCGCC		Primary dilated cardiomyopathy • Cardiovascular phenotype	Uncertain significance (May 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COMT	protein_coding	protein_coding	ENST00000361682	4	28369

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000114	0.206	125703	0	36	125739	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.429	157	173	0.908	0.0000110	1740
Missense in Polyphen		59	58.877	1.0021		577
Synonymous	0.445	76	81.1	0.937	0.00000579	568
Loss of Function	-0.0430	9	8.86	1.02	3.79e-7	97

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000127	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000153	0.000139
European (Non-Finnish)	0.000108	0.000105
Middle Eastern	0.0000544	0.0000544
South Asian	0.000589	0.000588
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:21846718}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:15645182}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.
• Pathway: Dopaminergic synapse - Homo sapiens (human);Steroid hormone biosynthesis - Homo sapiens (human);Tyrosine metabolism - Homo sapiens (human);Phenytoin Pathway, Pharmacokinetics;Estrogen Metabolism Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Tyrosinemia, transient, of the newborn;Dopamine beta-hydroxylase deficiency;Disulfiram Action Pathway;Tyrosine Metabolism;Alkaptonuria;Monoamine oxidase-a deficiency (MAO-A);Hawkinsinuria;Tyrosinemia Type I;Dopamine metabolism;Biogenic Amine Synthesis;Estrogen metabolism;Metapathway biotransformation Phase I and II;Methylation Pathways;Methylation;Phase II - Conjugation of compounds;dopamine degradation;Biological oxidations;Metabolism;L-dopa degradation;Neuronal System;Enzymatic degradation of dopamine by COMT;Enzymatic degradation of Dopamine by monoamine oxidase;Dopamine clearance from the synaptic cleft;Neurotransmitter clearance;Transmission across Chemical Synapses;Tyrosine metabolism;noradrenaline and adrenaline degradation (Consensus)

Recessive Scores

• pRec: 0.750

Intolerance Scores

• loftool: 0.748
• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.16

Haploinsufficiency Scores

• pHI: 0.137
• hipred: N
• hipred_score: 0.197
• ghis: 0.564

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Comt
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; embryo phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: female pregnancy;learning;short-term memory;estrogen metabolic process;response to organic cyclic compound;cellular response to phosphate starvation;methylation;response to lipopolysaccharide;developmental process;negative regulation of renal sodium excretion;neurotransmitter catabolic process;dopamine metabolic process;dopamine catabolic process;catecholamine catabolic process;response to drug;response to estrogen;negative regulation of dopamine metabolic process;response to pain;multicellular organismal reproductive process;negative regulation of smooth muscle cell proliferation;positive regulation of homocysteine metabolic process;regulation of sensory perception of pain
• Cellular component: cytosol;plasma membrane;membrane;integral component of membrane;axon;dendrite;dendritic spine;intracellular membrane-bounded organelle;cell body;postsynaptic membrane;extracellular exosome
• Molecular function: magnesium ion binding;protein binding;methyltransferase activity;O-methyltransferase activity;catechol O-methyltransferase activity;L-dopa O-methyltransferase activity;orcinol O-methyltransferase activity