CYP2C19

cytochrome P450 family 2 subfamily C member 19, the group of Cytochrome P450 family 2

Basic information

Region (hg38): 10:94762680-94855547

Previous symbols: [ "CYP2C" ]

Links

ENSG00000165841 ∙ NCBI:1557 ∙ OMIM:124020 ∙ HGNC:2621 ∙ Uniprot:P33261 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Drug metabolism, CYP2C19-related	AD	Pharmacogenomic	Selection and dosing of medications (eg, aspirin, clopidogrel, escitalopram, imipramine, omeprazole, tamoxifen) may be affected by the presence of variants	General	6489416; 3739364; 1302040; 8195181; 9093256; 16413245; 18004210; 18024866; 17625515; 19706858; 19106083; 19193675; 20083681; 20223877; 20978260; 20979470; 21047200; 19884907; 20351750; 20492469; 20801498; 20826260; 21178986; 21262992; 21288102; 21392617; 21288105; 21358751; 21700758; 21716271; 21716274; 21854540; 22027650; 22088980; 22228204; 22462746; 23090703; 23089672

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP2C19 gene.

• not provided (12 variants)
• Inborn genetic diseases (10 variants)
• CYP2C19: no function (8 variants)
• CYP2C19: uncertain function (8 variants)
• CYP2C19: decreased function (6 variants)
• - (6 variants)
• CYP2C19: normal function (4 variants)
• Mephenytoin, poor metabolism of (4 variants)
• Proguanil, poor metabolism of (2 variants)
• not specified (1 variants)
• Clopidogrel response (1 variants)
• Acute coronary syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP2C19 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				2	3	5
missense			10		1	11
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	10	2	4

Variants in CYP2C19

This is a list of pathogenic ClinVar variants found in the CYP2C19 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-94762693-G-A		-	no classification for the single variant (-)
10-94762706-A-G		Mephenytoin, poor metabolism of • CYP2C19: no function	drug response (-)
10-94762712-C-T		-	no classification for the single variant (-)
10-94762715-T-C		-	no classification for the single variant (-)
10-94762755-T-C		CYP2C19: uncertain function	drug response (-)
10-94762760-A-C		CYP2C19: normal function	drug response (-)
10-94762788-A-T		CYP2C19: uncertain function	drug response (-)
10-94762804-C-T			Benign (May 12, 2018)
10-94762856-A-G		CYP2C19: decreased function	drug response (-)
10-94775106-C-T		CYP2C19: uncertain function	drug response (-)
10-94775121-C-T		CYP2C19: uncertain function	drug response (-)
10-94775133-G-A		not specified	Uncertain significance (Mar 29, 2023)
10-94775149-T-A		not specified	Uncertain significance (Sep 20, 2023)
10-94775160-G-C		CYP2C19: uncertain function	drug response (-)
10-94775185-A-G		CYP2C19: uncertain function	drug response (-)
10-94775367-A-G		CYP2C19: no function	drug response (-)
10-94775416-T-C		CYP2C19: no function	drug response (-)
10-94775450-T-C		not specified	Uncertain significance (Jan 26, 2023)
10-94775453-G-A		CYP2C19: no function	drug response (-)
10-94775488-C-A		not specified	Uncertain significance (Jan 20, 2023)
10-94775489-G-A		CYP2C19: decreased function	drug response (-)
10-94775507-G-A		CYP2C19: normal function	drug response (-)
10-94780574-G-C		CYP2C19: no function	drug response (-)
10-94780579-G-A		CYP2C19: uncertain function	drug response (-)
10-94780612-G-A		not specified	Uncertain significance (Oct 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP2C19	protein_coding	protein_coding	ENST00000371321	9	165107

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.49e-20	0.000128	124327	41	1380	125748	0.00567

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.37	378	269	1.41	0.0000145	3230
Missense in Polyphen		108	81.259	1.3291		1067
Synonymous	-3.50	138	94.7	1.46	0.00000465	929
Loss of Function	-1.63	25	17.6	1.42	7.43e-7	242

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00236	0.00236
Ashkenazi Jewish	0.00	0.00
East Asian	0.0644	0.0643
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000493	0.000492
Middle Eastern	0.0644	0.0643
South Asian	0.00441	0.00439
Other	0.00294	0.00294

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
• Pathway: Citalopram Pathway, Pharmacokinetics;Benzodiazepine Pathway, Pharmacokinetics;Serotonergic synapse - Homo sapiens (human);Drug metabolism - cytochrome P450 - Homo sapiens (human);Arachidonic acid metabolism - Homo sapiens (human);Linoleic acid metabolism - Homo sapiens (human);Chemical carcinogenesis - Homo sapiens (human);Carbamazepine Pathway, Pharmacokinetics;Imipramine/Desipramine Pathway, Pharmacokinetics;Imatinib Pathway, Pharmacokinetics/Pharmacodynamics;Statin Pathway - Generalized, Pharmacokinetics;Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics;Fluvastatin Pathway, Pharmacokinetics;Warfarin Pathway, Pharmacokinetics;Phenytoin Pathway, Pharmacokinetics;Tamoxifen Pathway, Pharmacokinetics;Gefitinib Pathway, Pharmacokinetics;Proton Pump Inhibitor Pathway, Pharmacokinetics;Clopidogrel Pathway, Pharmacokinetics;Fluoxetine Pathway, Pharmacokinetics;Clomipramine Pathway, Pharmacokinetics;Doxepin Pathway, Pharmacokinetics;Venlafaxine Pathway, Pharmacokinetics;Ibuprofen Pathway, Pharmacokinetics;Cyclophosphamide Pathway, Pharmacokinetics;Ibuprofen Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fluoxetine Action Pathway;Citalopram Action Pathway;Imipramine Action Pathway;Ibuprofen Metabolism Pathway;Clopidogrel Metabolism Pathway;Methadone Metabolism Pathway;Imipramine Metabolism Pathway;Citalopram Metabolism Pathway;Clopidogrel Action Pathway;Methadone Action Pathway;Venlafaxine Metabolism Pathway;Carbamazepine Metabolism Pathway;Clomipramine Metabolism Pathway;Cyclophosphamide Action Pathway;Doxepin Metabolism Pathway;Fluoxetine Metabolism Pathway;Cyclophosphamide Metabolism Pathway;Constitutive Androstane Receptor Pathway;Pregnane X Receptor pathway;Nuclear Receptors Meta-Pathway;Melatonin metabolism and effects;Cannabinoid receptor signaling;Liver steatosis AOP;Oxidation by Cytochrome P450;Tamoxifen metabolism;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE);Arachidonic acid metabolism;Xenobiotics;Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET);Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;Fatty acid metabolism;Tryptophan degradation;superpathway of tryptophan utilization;CYP2E1 reactions;melatonin degradation I;superpathway of melatonin degradation (Consensus)

Intolerance Scores

• loftool: 0.923
• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.82

Haploinsufficiency Scores

• pHI: 0.0499
• hipred: N
• hipred_score: 0.112

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.928

Gene Damage Prediction

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

Gene ontology

• Biological process: organic acid metabolic process;xenobiotic metabolic process;steroid metabolic process;monoterpenoid metabolic process;drug metabolic process;epoxygenase P450 pathway;exogenous drug catabolic process;heterocycle metabolic process;oxidation-reduction process;omega-hydroxylase P450 pathway
• Cellular component: cytoplasm;endoplasmic reticulum membrane;organelle membrane;intracellular membrane-bounded organelle
• Molecular function: monooxygenase activity;iron ion binding;arachidonic acid epoxygenase activity;steroid hydroxylase activity;oxidoreductase activity;oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen;oxygen binding;enzyme binding;heme binding