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GIFtS
-

CYP3A4 Gene

protein-coding GIFtS: 69
GCID: GC07M099355

cytochrome P450, family 3, subfamily A, polypeptide 4

(Previous names: cytochrome P450, subfamily IIIA (niphedipine oxidase),...)
(Previous symbol: CYP3A3)

Explore 132 diseases affiliated with
CYP3A4 via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Cytochrome P450, Family 3, Subfamily A, Polypeptide 4¹ ²		CP34²
CYP3A3¹ ² ³		CYP3A²
Cytochrome P450, Subfamily IIIA (Niphedipine Oxidase), Polypeptide 4¹ ²		HLP²
Albendazole Monooxygenase² ³		NF-25²
Albendazole Sulfoxidase² ³		P450C3²
Cytochrome P450 3A3² ³		P450PCN1²
Cytochrome P450 HLp² ³		Cytochrome P450 3A4²
Cytochrome P450 NF-25² ³		Cytochrome P450, Subfamily IIIA (Niphedipine Oxidase), Polypeptide 3²
Cytochrome P450-PCN1² ³		Glucocorticoid-Inducible P450²
Nifedipine Oxidase² ³		P450-III, Steroid Inducible²
Quinine 3-Monooxygenase² ³		EC 1.14.13.-³
Taurochenodeoxycholate 6-Alpha-Hydroxylase² ³		EC 1.14.13.157³
1,8-Cineole 2-Exo-Monooxygenase² ³		EC 1.14.13.32³
CYPIIIA3² ³		EC 1.14.13.67³
CYPIIIA4² ³		EC 1.14.13.97³
CP33²		EC 1.14.14.1⁸

External Ids:	HGNC: 2637¹	Entrez Gene: 1576²	Ensembl: ENSG00000160868⁷	OMIM: 124010⁵	UniProtKB: P08684³

Export aliases for CYP3A4 gene to outside databases

Previous GC identifers: GC07M097889 GC07M098952 GC07M098967 GC07M098968 GC07M098892 GC07M098999 GC07M099192 GC07M093991

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for CYP3A4:

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 and erythromycin. 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, Feb 2011)

UniProtKB/Swiss-Prot: CP3A4_HUMAN, P08684

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 performs a variety of oxidation reactions (e.g. caffeine

8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally

unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The

enzyme also hydroxylates etoposide

summary for CYP3A4:

Cytochrome P450 (CYP450) enzymes are a diverse group of catalysts that contains 57 members in humans. CYPs

are usually membrane-bound and are localized to the inner mitochondrial or endoplasmic reticular membrane.

CYPs have oxygenase activity and commonly catalyze redox reactions, involving the oxidation of the substrate

and reduction of water. This group of enzymes contain a heme ion within the active site, which is essential

for catalytic activity. CYPs have been found in all organisms tested and are ubiquitously expressed. They

are found at high levels in the liver, where they have an important role in metabolism of drugs and

endogenous toxic compounds (for example bilirubin). Most CYPs can metabolize numerous substrates and this

accounts for their major role in drug interactions. CYPs also have functions in steroid hormone synthesis,

cholesterol synthesis and vitamin D metabolism.

Gene Wiki entry for CYP3A4

PharmGKB "VIP" summary for CYP3A4

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000007.13 NC_018918.1 NT_007933.15 NT_079595.2

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the CYP3A4 gene promoter:
GR COUP-TF1 COUP HNF-4alpha2 HNF-4alpha1 GATA-6 COUP-TF STAT3 GR-alpha NF-kappaB1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): CYP3A4 promoter sequence

Search SABiosciences Chromatin IP Primers for CYP3A4

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat CYP3A4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 7q21.1 Ensembl cytogenetic band: 7q22.1 HGNC cytogenetic band: 7q21.1

CYP3A4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CYP3A4 gene location

GeneLoc information about chromosome 7 GeneLoc Exon Structure

GeneLoc location for GC07M099355: view genomic region (about GC identifiers)

Start:	99,354,604 bp from pter	End:	99,381,888 bp from pter
Size:	27,285 bases	Orientation:	minus strand

1 alternative location:

Chr7-,CRA_TCAG 98,714,417-98,741,612

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: CP3A4_HUMAN, P08684 (See protein sequence)

Recommended Name: Cytochrome P450 3A4

Size: 503 amino acids; 57343 Da

Cofactor: Heme group

Subcellular location: Endoplasmic reticulum membrane; Single-pass membrane protein. Microsome membrane; Single-pass

membrane protein

Miscellaneous: Chimeric transcripts, characterized by CYP3A43 exon 1 joined at canonical splice sites to distinct sets

of CYP3A4 exons, have been detected. All are possibly produced by trans-splicing. The chimeric transcripts exist in 3

different combinations: CYP3A43 exon 1 joined in frame to CYP3A4 exons 2-13, CYP3A43 exon 1 joined in frame to CYP3A4

exons 4-13 and CYP3A43 exon 1 joined in frame to CYP3A4 exon 7-13. The longest chimeric isoform (CYP3A43 exon 1 joined

to CYP3A4 exons 2-13) exhibits 6-beta-hydroxylase activity, while a shorter isoform (CYP3A43 exon 1 joined to CYP3A4

exons 4-13) does not. All chimeric transcripts are expressed at very low levels in the liver (PubMed:11726664)

6/9 PDB 3D structures from and Proteopedia for CYP3A4 (see all 9):

1TQN (3D)

1W0E (3D)

1W0F (3D)

1W0G (3D)

2J0D (3D)

2V0M (3D)

Secondary accessions: P05184 Q16757 Q9UK50

Explore the universe of human proteins at neXtProt for CYP3A4: NX_P08684

Post-translational modifications:

Polyubiquitinated in the presence of AMFR and UBE2G1 and also STUB1/CHIP and UBE2D1 (in vitro)¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P08684

4/15 DME Specific Peptides for CYP3A4 (P08684) (see all 15)

SVFTNRR

PGPTPLP

LLSPTFT

PTFTSGK

CYP3A4 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_001189784.1 NP_059488.2

ENSEMBL proteins:

ENSP00000337915 ENSP00000397208 ENSP00000346607

Reactome Protein details: P08684
Human Recombinant Protein Products:

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	Novus Biologicals CYP3A4 Proteins Novus Biologicals CYP3A4 Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for CYP3A4

Gene Ontology (GO): 5/6 cellular component terms (GO ID links to tree view) (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005737	cytoplasm	IDA	18446064
GO:0005789	endoplasmic reticulum membrane	TAS	--
GO:0005792	microsome	--	--
GO:0009986	cell surface	IDA	12493773
GO:0016021	integral to membrane	IEA	--

CYP3A4 for ontologies About GeneDecksing

CYP3A4 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of CYP3A4
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	Cell Signaling Technology (CST) Antibodies for CYP3A4
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Assay Products for CYP3A4:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for CYP3A4
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for CYP3A4

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

CYP3A4 for domains About GeneDecksing

4 InterPro domains/families:

IPR008072 Cyt_P450_E_CYP3A

IPR001128 Cyt_P450

IPR017972 Cyt_P450_CS

IPR002402 Cyt_P450_E_grp-II

Graphical View of Domain Structure for InterPro Entry P08684

ProtoNet protein and cluster: P08684

3 Blocks protein families:

IPB002401 E-class P450 group I signature

IPB002402 Group II E-class P450 signature

IPB008072 CYP3A P450 family signature

UniProtKB/Swiss-Prot: CP3A4_HUMAN, P08684

Similarity: Belongs to the cytochrome P450 family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: CP3A4_HUMAN, P08684

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 performs a variety of oxidation reactions (e.g. caffeine

8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally

unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The

enzyme also hydroxylates etoposide

Catalytic activity: Quinine + NADPH + O(2) = 3-hydroxyquinine + NADP(+) + H(2)O

Catalytic activity: Taurochenodeoxycholate + NADPH + O(2) = taurohyocholate + NADP(+) + H(2)O

Catalytic activity: Lithocholate + NADPH + O(2) = hyodeoxycholate + NADP(+) + H(2)O

Catalytic activity: Albendazole + NADPH + O(2) = albendazole S-oxide + NADP(+) + H(2)O

Catalytic activity: 1,8-cineole + NADPH + O(2) = 2-exo-hydroxy-1,8-cineole + NADP(+) + H(2)O

Induction: By glucocorticoids. Also induced to high levels in liver and other tissues by various foreign compounds,

including drugs, pesticides, and carcinogens

Genatlas biochemistry entry for CYP3A4:

cytochrome P450,family III,polypeptide 4 (niphedipine oxidase);highly expressed in the liver,see CYP3A@,with a

significant association of the wild type enzyme with epipodophyllotoxin-induced leukemogenesis

Enzyme Numbers (IUBMB): EC 1.14.13.32¹ EC 1.14.13.157¹ EC 1.14.14.1² EC 1.14.13.97¹ EC 1.14.13.-¹ EC 1.14.13.67¹

miRNA Products:		OriGene 3'-UTR Clone: CYP3A4 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat CYP3A4
		8/10 QIAGEN miScript miRNA Assays for microRNAs that regulate CYP3A4 (see all 10):
		hsa-miR-548j hsa-miR-548w hsa-miR-559 hsa-miR-548h hsa-miR-548i hsa-miR-548c-5p hsa-miR-548y hsa-miR-548b-5p

		SwitchGear 3'UTR luciferase reporter plasmid: CYP3A4 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
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Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for CYP3A4

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Cell Line Products:		GenScript Custom overexpressing Cell Line Services for CYP3A4
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CYP3A4

Gene Ontology (GO): 5/18 molecular function terms (GO ID links to tree view) (see all 18): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004497	monooxygenase activity	ISS	--
GO:0005496	steroid binding	IDA	15256616
GO:0005506	iron ion binding	IDA	15256616
GO:0008395	steroid hydroxylase activity	IMP	18356043
GO:0009055	electron carrier activity	IEA	--

CYP3A4 for ontologies About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/39 super-pathways (see all 39) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Ifosfamide Pathway, Pharmacokinetics

Ifosfamide Pathway, Pharmacokinetics	1.00	Artemisinin and Derivatives Pathway, Pharmacokinetics	0.50
Cyclophosphamide Pathway, Pharmacokinetics	0.86	Clopidogrel Pathway, Pharmacokinetics	0.36
Sorafenib Pharmacokinetics	0.50	Losartan Pathway, Pharmacokinetics	0.22
Nevirapine Pathway, Pharmacokinetics	0.50

Estrone metabolism

Estrone metabolism	1.00	Androstenedione and testosterone biosynthesis and metabolism p.1	0.57
Estrone metabolism	1.00	Estrogen biosynthesis	0.47
Androstenedione and testosterone biosynthesis and metabolism p.1	0.57	Estrogen biosynthesis	0.47

Citalopram Pathway, Pharmacokinetics

Citalopram Pathway, Pharmacokinetics	1.00	Fluoxetine Pathway, Pharmacokinetics	0.57
Pathway_PA166014758	0.67	Tacrolimus/Cyclosporine Pathway, Pharmacokinetics	0.33
Proton Pump Inhibitor Pathway, Pharmacokinetics	0.60	Vinka Alkaloid Pathway, Pharmacokinetics	0.15

Tamoxifen metabolism

Tamoxifen metabolism	1.00	Estradiol metabolism	0.52
Tamoxifen Pathway, Pharmacokinetics	0.68	Benzodiazepine Pathway, Pharmacokinetics	0.30
Estradiol metabolism	0.52

Irinotecan Pathway, Pharmacokinetics

	Irinotecan Pathway, Pharmacokinetics	1.00			Mycophenolic acid Pathway, Pharmacokinetics	0.50
	Irinotecan Pathway	0.73			Taxane Pathway, Pharmacokinetics	0.30

Pathway sources
See GeneCards unified pathways
Show all pathways

5/12 EMD Millipore Pathways for CYP3A4 (see all 12)

	Androstenedione and testosterone biosynthesis and metabolism p.1
	Estradiol metabolism
	Naphthalene metabolism
	Selected targets of GCR-alpha
	Estrone metabolism

1 Cell Signaling Technology (CST) Pathway for CYP3A4

Glucose / Energy Metabolism

5/11 GeneGo (Thomson Reuters) Pathways for CYP3A4 (see all 11)

	Estrogen biosynthesis
	Naphthalene metabolism
	Transcription Role of VDR in regulation of genes involved in osteoporosis
	Acetaminophen metabolism
	Estradiol metabolism

5/13 BioSystems Pathways for CYP3A4 (see all 13)

	Irinotecan Pathway
	Aflatoxin B1 metabolism
	cytochrome P450
	Codeine and morphine metabolism
	Estrogen metabolism

5 Reactome Pathways for CYP3A4

	Cytochrome P450 - arranged by substrate type
	Xenobiotics
	Metabolism
	Biological oxidations
	Phase 1 - Functionalization of compounds

5/42 PharmGKB Pathways for CYP3A4 (see all 42)

	Acetaminophen Pathway, Pharmacokinetics
	Anti-diabetic Drug Nateglinide Pathway, Pharmacokinetics
	Anti-diabetic Drug Repaglinide Pathway, Pharmacokinetics
	Artemisinin and Derivatives Pathway, Pharmacokinetics
	Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics

5/8 Kegg Pathways (Kegg details for CYP3A4) (see all 8):

	Steroid hormone biosynthesis
	Linoleic acid metabolism
	Retinol metabolism
	Metabolism of xenobiotics by cytochrome P450
	Drug metabolism - cytochrome P450

CYP3A4 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for CYP3A4

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/125 Interacting proteins for CYP3A4 (P08684³ ENSP00000337915⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 125)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
AMFR	Q9UKV5³, ENSP00000290649⁴	I2D: score=1 STRING: ENSP00000290649
STUB1	Q9UNE7³, ENSP00000219548⁴	I2D: score=1 STRING: ENSP00000219548
UGT2B7	P16662³, ENSP00000304811⁴	I2D: score=1 STRING: ENSP00000304811
BYSL	Q13895³	I2D: score=5
C9orf64	Q5T6V5³	I2D: score=5

About this table

Gene Ontology (GO): 5/15 biological process terms (GO ID links to tree view) (see all 15): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006629	lipid metabolic process	TAS	2492107
GO:0006706	steroid catabolic process	IMP	18356043
GO:0006805	xenobiotic metabolic process	TAS	--
GO:0008202	steroid metabolic process	IMP	3259858
GO:0008209	androgen metabolic process	TAS	19651758

CYP3A4 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

CYP3A4 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Compounds for CYP3A4 available from Tocris Bioscience About this table

Compound	Action	CAS #
PF 4981517	Selective CYP3A4 inhibitor	--

10/67 HMDB Compounds for CYP3A4 (see all 67) About this table

Compound	Synonyms	CAS #	PubMed Ids
11,12,15-THETA	11,12,15-Trihydroxyicosatrienoic acid (see all 5)	--	--
11,12-Epoxyeicosatrienoic acid	10-(3-(2-octenyl)oxiranyl)-5,8-Decadienoic acid (see all 15)	81276-02-0	--
11,14,15-THETA	(5Z,8Z,12E)-11,14,15-Trihydroxyeicosa-5,8,12-trienoic acid (see all 8)	--	--
11H-14,15-EETA	14,15-Ep-11-HETrE (see all 11)	219535-29-2	--
12,13-EpOME	Vernolic acid (see all 12)	--	--
13-HETE	13-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoate (see all 2)	151910-72-4	--
14,15-Epoxy-5,8,11-eicosatrienoic acid	(5Z,8Z,11Z)-14,15-Epoxyicosa-5.8.11-trienoic acid (see all 11)	81276-03-1	--
15(S)-HPETE	(5Z,8Z,11Z,13E)-(15S)-15-Hydroperoxyicosa-5,8,11,13-tetraenoate (see all 8)	70981-96-3	--
15H-11,12-EETA	15-Hydroxy-11,12-epoxyeicosatrienoic acid (see all 9)	877878-78-9	--
16(R)-HETE	16R-HETE (see all 4)	--	--

10/488 DrugBank Compounds for CYP3A4 (see all 488) About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Clopidogrel	--	113665-84-2	enzyme	substrate	15679472 15604326 19934256 14707025 12925453 14522569 12485953 19515014
Astemizole	--	68844-77-9	enzyme	substrate inhibitor	10597902 11259984 15133245 19934256 12662125 10592235 15684493
Midazolam	Dea No. 2884 (see all 4)	59467-70-8	enzyme	substrate inhibitor	12124305 15544435 12065442 9890159 20203109 12433827 19934256
Cerivastatin	Cerivastatin sodium (see all 2)	145599-86-6	enzyme	substrate inhibitor inducer	17178259 12433802 11523064 9172950 19934256 19515014
Ifosfamide	Asta Z 4942 (see all 10)	3778-73-2	enzyme	substrate inhibitor inducer	16702183 15919850 19934256 19515014 12136253 10348794
Telithromycin	--	191114-48-4	enzyme	substrate inhibitor	16199242 15598962 15792396 12149046 11601667 19934256
Amitriptyline	Amitriprolidine (see all 7)	50-48-6	enzyme	substrate	11259560 9131945 18359012 19934256 19515014
Atorvastatin	--	134523-00-5	enzyme	substrate inhibitor inducer	17178259 11038166 11523064 19934256 19515014
Citalopram	Citalopram Hydrobromide (see all 2)	59729-33-8	enzyme	substrate	10774624 9890159 19934256 11532381 19515014
Fluvastatin	Fluindostatin (see all 5)	93957-54-1	enzyme	substrate inhibitor inducer	11368292 19663817 19934256 10064574 19515014

10/146 Novoseek chemical compound relationships for CYP3A4 gene (see all 146) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
troleandomycin	91.4	86	9806945 (3), 8261428 (2), 11125847 (2), 11095572 (2) (see all 50)
1-hydroxymidazolam	88.3	19	8185679 (4), 15801939 (2), 10741627 (1), 8669558 (1) (see all 12)
ketoconazole	87.7	171	9929500 (4), 10801218 (4), 19077665 (4), 16133532 (3) (see all 99)
midazolam	87.2	359	7965755 (5), 8185679 (5), 7828377 (5), 16842393 (5) (see all 99)
androstane	86.2	25	16513849 (2), 17392393 (2), 17041008 (2), 15466163 (1) (see all 22)
6beta-hydroxycortisol	85.5	36	9753209 (2), 14605865 (2), 15298747 (2), 10463384 (2) (see all 22)
rifampicin	85	374	17998298 (5), 16324277 (5), 20201776 (4), 11336975 (4) (see all 99)
6beta-hydroxytestosterone	84.9	11	17581220 (1), 18094037 (1), 15037195 (1), 10497147 (1) (see all 8)
citco	84.7	10	17585873 (1), 18347084 (1), 19202563 (1)
furafylline	82	13	8261428 (2), 15184267 (1), 16510126 (1), 9431831 (1) (see all 7)

10/15 PharmGKB related drug/compound annotations for CYP3A4 gene (see all 15)

Drug/compound	PharmGKB Annotation
aripiprazole	DL
cyclophosphamide	CA
docetaxel	CA
efavirenz	CA
fluvoxamine	DL
gefitinib	DL
indinavir	CA
midazolam	CA
nifedipine	CA
paclitaxel	CA

About this table

Search CenterWatch for drugs/clinical trials and news about CYP3A4 / CP3A4

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
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REFSEQ mRNAs for CYP3A4 gene (4 alternative transcripts):

NM_001202855.2 NM_017460.5 NM_001202856.1 NM_001202857.1

Unigene Cluster for CYP3A4:

Cytochrome P450, family 3, subfamily A, polypeptide 4

Hs.728751 [show with all ESTs]

Unigene Representative Sequence: NM_017460

4 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000336411 ENST00000480043 ENST00000415003 ENST00000354593(uc003urv.2 uc003urw.2 uc011kiz.2)

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Additional cDNA sequence:

AF182273.1 AJ563375.1 AJ563376.1 AJ563377.1 AK312967.1 AY606313.2 BC069352.1 BC069418.1

BC101631.1 DQ924960.1 M14096.1 M18907.1 X12387.1

18 DOTS entries:

DT.86852386 DT.91933736 DT.92456503 DT.86855768 DT.100808524 DT.100808520 DT.92456533 DT.100775927

DT.100808527 DT.91804891 DT.92456519 DT.100643862 DT.92456530 DT.95370344 DT.100742103 DT.100775926

DT.102845494 DT.95370347

24/189 AceView cDNA sequences (see all 189):

BG193807 BG194898 AV652769 CB156859 BG203510 AV650798 AV646302 AV646885

AV648762 NM_017460 AV650291 BC069418 AV660672 AV650997 AV647128 CB157183

AV647783 CB164407 AV659777 CB161712 AV652772 AV648960 AV650685 AV650321

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

CYP3A4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: --

About this image

CYP3A4 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

1 LifeMap In Vivo Development Anatomical Compartment/Cell

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Liver

Liver Lobule

Mature Hepatocytes

Liver

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 3 LifeMap Cells

Name

Category

Hepatocytes (Primary Cell)

Liver

Hepatocyte-like cells (Functional hepatocyt...)

Immature hepatocyte-like cells (Generation of hepato...)

See CYP3A4 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for CYP3A4

SOURCE GeneReport for Unigene cluster: Hs.728751

UniProtKB/Swiss-Prot: CP3A4_HUMAN, P08684

Tissue specificity: Expressed in prostate and liver. According to some authors, it is not expressed in brain

(PubMed:19094056). According to others, weak levels of expression are measured in some brain locations

(PubMed:19359404 and PubMed:18545703). Also expressed in epithelium of the small intestine and large intestine, bile

duct, nasal mucosa, kidney, adrenal cortex, epithelium of the gastric mucosa with intestinal metaplasia, gallbladder,

intercalated ducts of the pancreas, chief cells of the parathyroid and the corpus luteum of the ovary (at protein

level)

SABiosciences Expression via Pathway-Focused PCR Arrays including CYP3A4:

Cancer Drug Resistance in human mouse rat

Drug Metabolism: Phase I Enzymes in human mouse rat

Cellular Stress Responses in human mouse rat

Molecular Toxicology PathwayFinder 384HT in human mouse rat

Drug Metabolism in human mouse rat

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of eukaryotes.

Orthologs for CYP3A4 gene from 8/23 species (see all 23) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	CYP3A4¹	cytochrome P450, family 3, subfamily A, polypeptide more	63.04(n) 61.09(a)		416477 XM_414782.3 XP_414782.1
lizard (Anolis carolinensis)	Reptilia	--	--	55(a)	1 → many	GL343987.1(114011-127496)
African clawed frog (Xenopus laevis)	Amphibia	MGC68821²	hypothetical protein MGC68821	75.25(n)		BC060496.1
zebrafish (Danio rerio)	Actinopterygii	cyp3a65¹	cytochrome P450, family 3, subfamily A, polypeptide more	61.33(n) 57.91(a)		553969 NM_001037438.1 NP_001032515.1
fruit fly (Drosophila melanogaster)	Insecta	Cyp6a23³	cytochrome P450	35(a) (best of 36)		51D1 --
worm (Caenorhabditis elegans)	Secernentea	F14F7.3³ cyp-25A3¹	cytochrome P450³ Protein CYP-25A3¹	32(a) (best of 14)³ 47.11(n)¹ 32.53(a)¹		III(13095916-13099217)³ 4363046¹ NM_001047385.1¹ NP_001040850.1¹
thale cress (Arabidopsis thaliana)	eudicotyledons	CYP711A1¹	cytochrome P450, family 711, subfamily A, polypeptide more	44.68(n) 30.44(a)		817157 NM_128175.3 NP_565617.2
rice (Oryza sativa)	Liliopsida	Os01g0700900¹	hypothetical protein	46.15(n) 35.58(a)		4326926 NM_001050521.1 NP_001043986.1

ENSEMBL Gene Tree for CYP3A4 (if available)
TreeFam Gene Tree for CYP3A4 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for CYP3A4 gene

CYP4F22² CYP4F3² CYP4F2² CYP4F11² CYP46A1² ENSG00000225607² CYP4B1² CYP3A5²

CYP4X1² TBXAS1² CYP3A43² CYP3A7² CYP4V2² CYP4A22² CYP4A11² CYP4F12²

CYP4Z1²

18 SIMAP similar genes for CYP3A4 using alignment to 5 protein entries: CP3A4_HUMAN (see all proteins):

CYP3A43/CYP3A4 CYP3A5 CYP3A7 CYP3A43 CYP4A11 CYP4B1

TBXAS1 thromboxane synthase CYP2E1 CYP4V2 CYP19A1 CYP1A1

CYP2C9 CYP4F3 CYP4F12 CYP21A2 CYP2G1P CYP4F11

CYP3A4 for paralogs About GeneDecksing

3 Pseudogenes.org Pseudogenes for CYP3A4
PGOHUM00000232935 PGOHUM00000263172 PGOHUM00000232936

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 7 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs28988583^1,2	C,F,	--	94003137(-)	`CATTAT/CATTTT`	2	--	int¹		8		NS CSA WA	310
rs13312080^1,2		--	94003145(+)	`ATGACA/CAATAA`	2	--	int¹		0	--	--	--	--
rs13312028^1,2		--	94003149(+)	`CCAATA/GATGTC`	2	--	int¹		0	--	--	--	--
rs13312442^1,2		--	94003220(+)	`ATCCCC/TGGTCT`	2	--	int¹		0	--	--	--	--
rs13312168^1,2		--	94003221(+)	`TCCCTG/TGTCTG`	2	--	int¹		0	--	--	--	--
rs13312044^1,2		--	94003236(+)	`GGACAA/GACTCA`	2	--	int¹		0	--	--	--	--
rs13312046^1,2		--	94003237(+)	`GACAAA/GCTCAG`	2	--	int¹		0	--	--	--	--
rs13312492^1,2		--	94003255(+)	`CTGTTG/TTTACT`	2	--	int¹		0	--	--	--	--
rs13312092^1,2		--	94003258(+)	`TTTTTA/CCTGCA`	2	--	int¹		0	--	--	--	--
rs13312494^1,2		--	94003274(+)	`GTAGAC/TAGCAA`	2	--	int¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for CYP3A4 (99354604 - 99381888 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for CYP3A4: --
Human Gene Mutation Database (HGMD): CYP3A4

Locus Specific Mutation Databases (LSDB): CYP3A4

SABiosciences Cancer Mutation PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

CYP3A4 for disorders           About GeneDecksing

OMIM gene information: 124010    OMIM disorders: --

20/132 diseases for CYP3A4 (see all 132):    About MalaCards

21-hydroxylase deficiency estrogen-receptor positive breast cancer antley-bixler syndrome gastroesophageal reflux disease

cerebrotendinous xanthomatosis human immunodeficiency virus infectious disease cholesterol xanthomatosis

dengue hemorrhagic fever precocious puberty status epilepticus intrahepatic cholestasis

tardive dyskinesia anxiety disorder type 2 diabetes mellitus testicular germ cell cancer

hemorrhagic fever substance abuse intrahepatic cholestasis of pregnancy beta thalassemia

2 diseases from the University of Copenhagen DISEASES database for CYP3A4:

Liver disease Diarrhea

10/89 Novoseek disease relationships for CYP3A4 gene (see all 89) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
acetaminophen metabolism	52.5	1	10678302 (1)
rhabdomyolysis	46.3	5	11856903 (1), 16581331 (1), 11149552 (1), 19734738 (1)
colon carcinoma	32.8	18	12419308 (2), 14615069 (2), 12625868 (2), 12738030 (1) (see all 13)
immunodeficiency	30.4	15	12189360 (1), 15657782 (1), 16433896 (1), 14985144 (1) (see all 11)
torsades de pointes	23.6	5	15762770 (1), 9545159 (1), 12949438 (1)
liver diseases	21.5	4	7741759 (1), 9131486 (1), 9927612 (1), 19620337 (1)
colon adenocarcinoma	18.8	4	18332086 (1), 9822896 (1), 10871337 (1), 11602520 (1)
liver dysfunction	18.7	2	12867215 (1), 18183036 (1)
neutropenia	17	4	17992531 (2), 19696793 (1), 20068078 (1)
cholestasis	14.9	5	15454728 (1), 16455805 (1), 15726657 (1), 15708356 (1)

Genetic Association Database (GAD): CYP3A4
Human Genome Epidemiology (HuGE) Navigator: CYP3A4 (383 documents)

Export disorders for CYP3A4 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for CYP3A4 gene, integrated from 9 sources (see all 2188):
(articles sorted by number of sources associating them with CYP3A4)

Utopia: connect your pdf to the dynamic
world of online information

Recombinant CYP3A4*17 is defective in metabolizing the hypertensive drug nifedipine, and the CYP3A4*17 allele may occur on the same chromosome as CYP3A5*3, representing a new putative defective CYP3A haplotype. (PubMed id 15634941)^{1, 4, 7} Lee S.J....Goldstein J.A. (2005)
Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. (PubMed id 11714865)^{1, 2, 4} Dai D.... Goldstein J.A. (2001)
Novel mutations of CYP3A4 in Chinese. (PubMed id 11181494)^{1, 2, 4} Hsieh K.-P.... Huang J.-D. (2001)
Regulation of CYP3A4 by the bile acid receptor FXR: evidence for functional binding sites in the CYP3A4 gene. (PubMed id 15454728)^{1, 7, 9} Gnerre C....Meyer U.A. (2004)
Phthalate induction of CYP3A4 is dependent on glucocorticoid regulation of PXR expression. (PubMed id 18332045)^{1, 7, 9} Cooper B.W....Wallace A.D. (2008)
Relative impact of CYP3A genotype and concomitant medication on the severity of atorvastatin-induced muscle damage. (PubMed id 15900215)^{1, 4, 9} Wilke R.A....Burmester J.K. (2005)
CYP3A4 and CYP3A5 genotyping by Pyrosequencing. (PubMed id 15882469)^{1, 4, 9} Garsa A.A....Marsh S. (2005)
Effect of common CYP3A4 and CYP3A5 variants on the pharmacokinetics of the cytochrome P450 3A phenotyping probe midazolam in cancer patients. (PubMed id 16243813)^{1, 4, 9} Lepper E.R....Sparreboom A. (2005)
Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 polymorphisms with the pharmacokinetics of paclitaxel. (PubMed id 16299241)^{1, 4, 9} Henningsson A....McLeod H.L. (2005)
Genotype-phenotype associations of cytochrome P450 3A4 and 3A5 polymorphism with midazolam clearance in vivo. (PubMed id 15900284)^{1, 4, 9} He P....Von Moltke L.L. (2005)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 1576	HGNC: 2637	AceView: CYP3A4	Ensembl:ENSG00000160868	euGenes: HUgn1576
ECgene: CYP3A4	Kegg: 1576	H-InvDB: CYP3A4

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for CYP3A4	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for CYP3A4	Genetics and Cytogenetics in Oncology and Haematology
Cytochrome P450 Allele Nomenclature Committee	http://www.cypalleles.ki.se/cyp3a4.htm
Wikipedia	http://en.wikipedia.org/wiki/CYP3A4

Intellectual Property for CYP3A4 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for CYP3A4 gene:
Search GeneIP for patents involving CYP3A4

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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cytochrome P450, family 3, subfamily A, polypeptide 4

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CYP3A4 (Gene Symbol)
Cytochrome P450, Family 3, Subfamily A, Polypeptide 4
CYP3A3
Cytochrome P450, Subfamily IIIA (Niphedipine Oxidase), Polypeptide 4
Albendazole Monooxygenase
Albendazole Sulfoxidase
Cytochrome P450 3A3
Cytochrome P450 HLp
Cytochrome P450 NF-25
Cytochrome P450-PCN1
Nifedipine Oxidase
Quinine 3-Monooxygenase
Taurochenodeoxycholate 6-Alpha-Hydroxylase
1,8-Cineole 2-Exo-Monooxygenase
CYPIIIA3
CYPIIIA4
CP33
CP34
CYP3A
HLP
NF-25
P450C3
P450PCN1
Cytochrome P450 3A4
Cytochrome P450, Subfamily IIIA (Niphedipine Oxidase), Polypeptide 3
Glucocorticoid-Inducible P450
P450-III, Steroid Inducible
EC 1.14.13.-
EC 1.14.13.157
EC 1.14.13.32
EC 1.14.13.67
EC 1.14.13.97
EC 1.14.14.1

Fatty Liver
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CYP3A4 Gene

cytochrome P450, family 3, subfamily A, polypeptide 4

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Aliases
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Proteins
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for CYP3A4 gene

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Pathways & Interactions
for CYP3A4 gene

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