CYP2C9

protein-coding

cytochrome P450 family 2 subfamily C member 9, 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 its expression is induced by rifampin. The enzyme is known to metabolize many xenobiotics, including phenytoin, tolbutamide, ibuprofen and S-warfarin. Studies identifying individuals who are poor metabolizers of phenytoin and tolbutamide suggest that this gene is polymorphic. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. [provided by RefSeq, Jul 2008]

Previous symbols:

CYP2C10

MANE transcript

NM_000771.4

Inheritance

ClinVar variants

P:1U:42B:13

Top phenotype

Drug metabolism, CYP2C9-related

gnomAD constraint

pLI —, LoF o/e 0.92

Max pathogenic AF

—

Genomic locus

chr10:94,938,658-94,990,091

External References & Databases

Ensembl (ENSG00000138109)

Transcript & Mutation Effects

hg38 • Region Span ~51.4 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, CYP2C9-relatedAD

Manifestation: General

Intervention: Pharmacogenomic

Rationale: Selection and dosing of medications may be affected by the presence of variants

Refs: 10073515; 10901705; 19228618; 19300499; 19715737; 19794412; 20089352; 20402581; 21562147; 23089672

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYP2C9 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 41

not providedTotal: 11

Warfarin responseTotal: 6

Piroxicam responseTotal: 4

Lesinurad responseTotal: 4

Flurbiprofen responseTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000771.4. 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				5 clinvar	1 clinvar	6
missense	1 clinvar		41 clinvar	4 clinvar	2 clinvar	48
nonsense			1 clinvar			1
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)						0
Total	1	0	42	10	3	56

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000771.4	RefSeq	NP_000762.2	9	MANE Select
ENST00000260682.8	Ensembl	ENSP00000260682.6	9	MANE Select
ENST00000461906.1	Ensembl	ENSP00000495649.1	3	Standard
ENST00000461906.2	Ensembl	ENSP00000495649.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Celecoxib Pathway, Pharmacokinetics
Rosiglitazone Pharmacokinetic Pathway
Retinol metabolism - Homo sapiens (human)
Serotonergic synapse - Homo sapiens (human)
Metabolism of xenobiotics by cytochrome P450 - 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
drug binding
arachidonic acid epoxygenase activity
steroid hydroxylase 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: ENST00000260682
Coding exons: 9
Length: 50733
Individuals with no LoFs: 125665
Homozygous LoFs: 0
Heterozygous LoFs: 78
Defined: 125743
p: 0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.94	381	250	1.52	0.0000130	3242
Missense (PolyPhen)		125	82.504	1.5151		1094
Synonymous	-4.07	141	91.4	1.54	0.00000459	929
Loss of Function	0.295	16	17.3	0.924	7.43e-7	248

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0013	0.0013	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00086	0.00085	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics (PubMed:25994031). This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031). {ECO:0000269|PubMed:25994031}.;

Recessive Scores

pRec: 0.383

Intolerance Scores

LoFtool: 0.903
RVIS EVS: 0.31
RVIS percentile EVS: 72.71

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.937

Gene Damage Prediction

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