CYP3A4 cytochrome P450 family 3 subfamily A member 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CYP3A4provided by HGNC
Official Full Name: cytochrome P450 family 3 subfamily A member 4provided by HGNC
Primary source: HGNC:HGNC:2637
See related: Ensembl:ENSG00000160868 MIM:124010; AllianceGenome:HGNC:2637
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HLP; CP33; CP34; CYP3A; NF-25; VDDR3; CYP3A3; P450C3; CYPIIIA3; CYPIIIA4; P450PCN1
Summary: This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that 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 glucocorticoids and some pharmacological agents. This enzyme is involved in the metabolism of approximately half the drugs in use today, including acetaminophen, codeine, cyclosporin A, diazepam, erythromycin, and chloroquine. The enzyme also metabolizes some steroids and carcinogens. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Previously another CYP3A gene, CYP3A3, was thought to exist; however, it is now thought that this sequence represents a transcript variant of CYP3A4. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2020]
Expression: Biased expression in liver (RPKM 476.5), small intestine (RPKM 282.8) and 1 other tissue See more
Orthologs: all
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Genomic context

Location:: 7q22.1

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (99756967..99784184, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (100996482..101023683, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (99354590..99381807, complement)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

DNA methylation determines the regulation of pregnane X receptor on CYP3A4 expression.
Title: DNA methylation determines the regulation of pregnane X receptor on CYP3A4 expression.
Genetic variation present in the CYP3A4 gene in Ni-Vanuatu and Kenyan populations in malaria endemicity.
Title: Genetic variation present in the CYP3A4 gene in Ni-Vanuatu and Kenyan populations in malaria endemicity.
Effects of CYP3A4 genetic polymorphisms on the pharmacokinetics and efficacy of perampanel in Chinese pediatric patients with epilepsy.
Title: Effects of CYP3A4 genetic polymorphisms on the pharmacokinetics and efficacy of perampanel in Chinese pediatric patients with epilepsy.
Polymorphism of CYP3A4*18 is associated with anti-tuberculosis drug-induced hepatotoxicity.
Title: Polymorphism of CYP3A4*18 is associated with anti-tuberculosis drug-induced hepatotoxicity.
Probe Substrate Dependencies in CYP3A4 Allosteric Inhibition: A Novel Molecular Mechanism Involving F-F' Loop Perturbations.
Title: Probe Substrate Dependencies in CYP3A4 Allosteric Inhibition: A Novel Molecular Mechanism Involving F-F' Loop Perturbations.
Genetic variations of CYP3A4 on the metabolism of itraconazole in vitro.
Title: Genetic variations of CYP3A4 on the metabolism of itraconazole in vitro.
Functional maturation of cytochromes P450 3A4 and 2D6 relies on GAPDH- and Hsp90-Dependent heme allocation.
Title: Functional maturation of cytochromes P450 3A4 and 2D6 relies on GAPDH- and Hsp90-Dependent heme allocation.
Cyp3A4 *1G polymorphism is associated with alcohol drinking: A 5-year retrospective single centered population-based study in China.
Title: Cyp3A4 *1G polymorphism is associated with alcohol drinking: A 5-year retrospective single centered population-based study in China.
The long noncoding RNA HNF1A-AS1 with dual functions in the regulation of cytochrome P450 3A4.
Title: The long noncoding RNA HNF1A-AS1 with dual functions in the regulation of cytochrome P450 3A4.
The impacts of CYP3A4 genetic polymorphism and drug interactions on the metabolism of lurasidone.
Title: The impacts of CYP3A4 genetic polymorphism and drug interactions on the metabolism of lurasidone.

Submit: New GeneRIF Correction See all GeneRIFs (690)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Clozapine response MedGen: CN077971 GeneReviews: Not available	not available
Esomeprazole response MedGen: CN077982 GeneReviews: Not available	not available
Ondansetron response MedGen: CN417142 GeneReviews: Not available	not available
Vitamin D-dependent rickets, type 3 MedGen: C5436733 OMIM: 619073 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Human metabolic individuality in biomedical and pharmaceutical research. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:483113

CYP3A4_2210 (e-PCR)
- UniSTS:280639

CYP3A7_3262 (e-PCR)
- UniSTS:462149

CYPNOA (e-PCR)
- UniSTS:36431

D7S2832 (e-PCR)
- UniSTS:78468

D7S2874 (e-PCR)
- UniSTS:27061

SHGC-16521 (e-PCR)
- UniSTS:1733

SHGC-36965 (e-PCR)
- UniSTS:3533

RH68186 (e-PCR)
- UniSTS:2009

NoName (e-PCR)
- UniSTS:480483

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 1,8-cineole 2-exo-monooxygenase activity	IEA Inferred from Electronic Annotation more info
enables 1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity	IDA Inferred from Direct Assay more info	PubMed
enables anandamide 11,12 epoxidase activity	IEA Inferred from Electronic Annotation more info
enables anandamide 14,15 epoxidase activity	IEA Inferred from Electronic Annotation more info
enables anandamide 8,9 epoxidase activity	IEA Inferred from Electronic Annotation more info
enables caffeine oxidase activity	IDA Inferred from Direct Assay more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables estrogen 16-alpha-hydroxylase activity	IBA Inferred from Biological aspect of Ancestor more info
enables estrogen 16-alpha-hydroxylase activity	IDA Inferred from Direct Assay more info	PubMed
enables estrogen 2-hydroxylase activity	IDA Inferred from Direct Assay more info	PubMed
enables heme binding	IEA Inferred from Electronic Annotation more info
enables iron ion binding	IDA Inferred from Direct Assay more info	PubMed
enables monooxygenase activity	IDA Inferred from Direct Assay more info	PubMed
enables monooxygenase activity	ISS Inferred from Sequence or Structural Similarity more info
enables monooxygenase activity	TAS Traceable Author Statement more info
enables oxidoreductase activity	IDA Inferred from Direct Assay more info	PubMed
enables 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	IEA Inferred from Electronic Annotation more info
enables oxygen binding	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables quinine 3-monooxygenase activity	IEA Inferred from Electronic Annotation more info
enables retinoic acid 4-hydroxylase activity	IDA Inferred from Direct Assay more info	PubMed
enables steroid binding	IDA Inferred from Direct Assay more info	PubMed
enables steroid hydroxylase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables steroid hydroxylase activity	TAS Traceable Author Statement more info
enables testosterone 6-beta-hydroxylase activity	IBA Inferred from Biological aspect of Ancestor more info
enables testosterone 6-beta-hydroxylase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables vitamin D 24-hydroxylase activity	IDA Inferred from Direct Assay more info	PubMed
enables vitamin D3 25-hydroxylase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in aflatoxin metabolic process	TAS Traceable Author Statement more info
involved_in alkaloid catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in androgen metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in calcitriol biosynthetic process from calciol	IEA Inferred from Electronic Annotation more info
involved_in cholesterol metabolic process	IEA Inferred from Electronic Annotation more info
involved_in estrogen metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in lipid hydroxylation	IDA Inferred from Direct Assay more info	PubMed
involved_in lipid metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in long-chain fatty acid biosynthetic process	TAS Traceable Author Statement more info
involved_in monoterpenoid metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in oxidative demethylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in oxidative demethylation	IDA Inferred from Direct Assay more info	PubMed
involved_in retinoic acid metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in retinol metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in retinol metabolic process	IEA Inferred from Electronic Annotation more info
involved_in steroid catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in steroid metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in steroid metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in steroid metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vitamin D catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in vitamin D metabolic process	IC Inferred by Curator more info	PubMed
involved_in xenobiotic catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in xenobiotic catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in xenobiotic metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in xenobiotic metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in intracellular membrane-bounded organelle	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: cytochrome P450 3A4

Names: 1,4-cineole 2-exo-monooxygenase; 1,8-cineole 2-exo-monooxygenase; P450-III, steroid inducible; albendazole monooxygenase (sulfoxide-forming); albendazole sulfoxidase; cholesterol 25-hydroxylase; cytochrome P450 3A3; cytochrome P450 HLp; cytochrome P450 NF-25; cytochrome P450, family 3, subfamily A, polypeptide 4; cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 3; cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 4; cytochrome P450-PCN1; glucocorticoid-inducible P450; nifedipine oxidase; quinine 3-monooxygenase; taurochenodeoxycholate 6-alpha-hydroxylase

NP_001189784.1

EC 1.14.14.1

EC 1.14.14.55

EC 1.14.14.56

EC 1.14.14.73

NP_059488.2

EC 1.14.14.1

EC 1.14.14.55

EC 1.14.14.56

EC 1.14.14.73

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008421.1 RefSeqGene

Range

5002..32219

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001202855.3 → NP_001189784.1 cytochrome P450 3A4 isoform 2

See identical proteins and their annotated locations for NP_001189784.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the CDS compared to variant 1. The resulting isoform (2) is shorter but has the same N- and C-termini compared to isoform 1.

Source sequence(s)

AC069294, BC101631, J04449

UniProtKB/TrEMBL

Q86SK3

Conserved Domains (1) summary

pfam00067
Location:39 → 492

p450; Cytochrome P450
NM_017460.6 → NP_059488.2 cytochrome P450 3A4 isoform 1

See identical proteins and their annotated locations for NP_059488.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC069294, AK312967

Consensus CDS

CCDS5674.1

UniProtKB/Swiss-Prot

P05184, P08684, Q16757, Q9UK50

UniProtKB/TrEMBL

Q6GRK0, Q86SK3

Related

ENSP00000498939.1, ENST00000651514.1

Conserved Domains (1) summary

pfam00067
Location:39 → 493

p450; Cytochrome P450

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000007.14 Reference GRCh38.p14 Primary Assembly

Range

99756967..99784184 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060931.1 Alternate T2T-CHM13v2.0

Range

100996482..101023683 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001202856.1: Suppressed sequence

Description

NM_001202856.1: This RefSeq was permanently suppressed because it represents a product of trans-splicing and is not in scope for the RefSeq collection.
NM_001202857.1: Suppressed sequence

Description

NM_001202857.1: This RefSeq was permanently suppressed because it represents a product of trans-splicing and is not in scope for the RefSeq collection.