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

Gene ID: 1576, updated on 27-Nov-2024

Summary

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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

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See CYP3A4 in Genome Data Viewer
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_000007.14Genomic Context describing neighboring genes Neighboring gene zinc finger and SCAN domain containing 25 Neighboring gene CYP3A7-CYP3A51P readthrough Neighboring gene cytochrome P450 family 3 subfamily A member 7 Neighboring gene CYP3A7 5' regulatory region Neighboring gene enhancer in intron 10 of CYP3A4 Neighboring gene cytochrome P450, family 3, subfamily A, polypeptide 5 pseudogene 2 Neighboring gene CYP3A4 5' regulatory region Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:99406501-99407104 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:99407105-99407707 Neighboring gene cytochrome P450 family 3 subfamily A member 137, pseudogene Neighboring gene cytochrome P450 family 3 subfamily A member 43 Neighboring gene MPRA-validated peak6657 silencer

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Pharmacokinetic interactions of almorexant with midazolam and simvastatin, two CYP3A4 model substrates, in healthy male subjects. Hoch M, et al. Eur J Clin Pharmacol, 2013 Mar. PMID 22990330
  2. Stereospecific metabolism of itraconazole by CYP3A4: dioxolane ring scission of azole antifungals. Peng CC, et al. Drug Metab Dispos, 2012 Mar. PMID 22106171, Free PMC Article
  3. Structural and mechanistic insights into the interaction of cytochrome P4503A4 with bromoergocryptine, a type I ligand. Sevrioukova IF, et al. J Biol Chem, 2012 Jan 27. PMID 22157006, Free PMC Article
  4. Peripheral ligand-binding site in cytochrome P450 3A4 located with fluorescence resonance energy transfer (FRET). Davydov DR, et al. J Biol Chem, 2012 Feb 24. PMID 22194603, Free PMC Article
  5. The new CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) is associated with an increased risk of delayed graft function and worse renal function in cyclosporine-treated kidney transplant patients. Elens L, et al. Pharmacogenet Genomics, 2012 May. PMID 22388796

See all (965) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. Genetic variations of CYP3A4 on the metabolism of itraconazole in vitro.
    Title: Genetic variations of CYP3A4 on the metabolism of itraconazole in vitro.
  7. 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.
  8. 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.
  9. 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.
  10. 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
Compare labs
Esomeprazole response
MedGen: CN077982 GeneReviews: Not available
Compare labs
Ondansetron response
MedGen: CN417142 GeneReviews: Not available
Compare labs
Vitamin D-dependent rickets, type 3
MedGen: C5436733 OMIM: 619073 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

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

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

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC126680

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
NP_059488.2

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

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

  1. NG_008421.1 RefSeqGene

    Range
    5002..32219
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    99756967..99784184 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. 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

  1. 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.

  2. 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.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P08684.4 GenPept UniProtKB/Swiss-Prot:P08684

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Molecular Biology Databases
Research Materials
Tools
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