CYP2C19

protein-coding

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

Gene summary

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, omeprazole, diazepam and some barbiturates. Polymorphism within this gene is associated with variable ability to metabolize mephenytoin, known as the poor metabolizer and extensive metabolizer phenotypes. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. [provided by RefSeq, Jul 2008]

Previous symbols:

CYP2C

MANE transcript

NM_000769.4

Inheritance

ClinVar variants

U:55B:11

Top phenotype

Drug metabolism, CYP2C19-related

gnomAD constraint

pLI —, LoF o/e 1.42

Max pathogenic AF

—

Genomic locus

chr10:94,762,681-94,855,547

External References & Databases

Ensembl (ENSG00000165841)

Transcript & Mutation Effects

hg38 • Region Span ~92.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Drug metabolism, CYP2C19-relatedAD

Manifestation: General

Intervention: Pharmacogenomic

Rationale: Selection and dosing of medications (eg, aspirin, clopidogrel, escitalopram, imipramine, omeprazole, tamoxifen) may be affected by the presence of variants

Refs: 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

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYP2C19 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 50

not providedTotal: 8

CYP2C19: no functionTotal: 6

MEPHENYTOIN, POOR METABOLISM OFTotal: 3

Acute coronary syndromeTotal: 2

Clopidogrel responseTotal: 1

CYP2C19: decreased functionTotal: 1

PROGUANIL, POOR METABOLISM OFTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000769.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	8 clinvar	1 clinvar	12
missense			49 clinvar	2 clinvar		51
nonsense			1 clinvar			1
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	55	10	1	66

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000769.4	RefSeq	NP_000760.1	9	MANE Select
ENST00000371321.9	Ensembl	ENSP00000360372.3	9	MANE Select
ENST00000480405.2	Ensembl	ENSP00000483847.1	3	Standard
ENST00000480405.3	Ensembl	ENSP00000483847.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Citalopram Pathway, Pharmacokinetics
Benzodiazepine Pathway, Pharmacokinetics
Serotonergic synapse - Homo sapiens (human)
Drug metabolism - cytochrome P450 - Homo sapiens (human)
Arachidonic acid metabolism - Homo sapiens (human)

Biological Process

organic acid metabolic process
xenobiotic metabolic process
steroid metabolic process
monoterpenoid metabolic process
drug metabolic process

Molecular Function

monooxygenase activity
iron ion binding
arachidonic acid epoxygenase activity
steroid hydroxylase activity
oxidoreductase activity

Cellular Component

cytoplasm
endoplasmic reticulum membrane
organelle membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371321
Coding exons: 9
Length: 165107
Individuals with no LoFs: 124327
Homozygous LoFs: 41
Heterozygous LoFs: 1380
Defined: 125748
p: 0.00567

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.37	378	269	1.41	0.0000145	3230
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00074	rare
Latino/Admixed American	0.0016	0.0016	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.064	0.064	notable
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00049	0.00049	rare
South Asian	0.0044	0.0044	notable
Other	0.0029	0.0029	notable

dbNSFP Gene Annotations

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.;

Intolerance Scores

LoFtool: 0.923
RVIS EVS: 0.71
RVIS percentile EVS: 85.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.928

Gene Damage Prediction

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