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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

CYP3A4 Gene

protein-coding   GIFtS: 71
GCID: GC07M099355

Cytochrome P450, Family 3, Subfamily A, Polypeptide 4

(Previous names: cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide...)
(Previous symbol: CYP3A3)
Microbiology & Infectious Diseases Congress
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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 Gene:
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)

GeneCards Summary for CYP3A4 Gene: 
CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4) is a protein-coding gene. Diseases associated with CYP3A4 include cytochrome p450, and xanthomatosis, and among its related super-pathways are Tamoxifen Pathway, Pharmacokinetics and Irinotecan Pathway. GO annotations related to this gene include iron ion binding and enzyme binding. An important paralog of this gene is CYP4F22.

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 Gene:
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 Gene

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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000007.13  NC_018918.2  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:
99,354,583 bp from pter      End:
99,381,888 bp from pter
Size:
27,306 bases      Orientation:
minus strand

1 alternative location:
Chr7-,CRA_TCAG 98,714,396-98,741,615     

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB 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 Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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)
6/12 PDB 3D structures from and Proteopedia for CYP3A4 (see all 12):
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

Explore proteomics data for CYP3A4 at MOPED 

Post-translational modifications:

  • UniProtKB: Polyubiquitinated in the presence of AMFR and UBE2G1 and also STUB1/CHIP and UBE2D1 (in vitro)
  • View modification sites using PhosphoSitePlus
  • 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 MOPED1, PaxDb2 and MAXQB3 :    About this image 

    CYP3A4 Protein Expression
    REFSEQ proteins (2 alternative transcripts): 
    NP_001189784.1  NP_059488.2  

    ENSEMBL proteins: 
     ENSP00000337915   ENSP00000397208   ENSP00000346607  
    Reactome Protein details: P08684
    Human Recombinant Protein Products for CYP3A4: 
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    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for CYP3A4 

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm IDA18446064
    GO:0005789endoplasmic reticulum membrane TAS--
    GO:0009986cell surface IDA12493773
    GO:0016021integral to membrane IEA--
    GO:0043231intracellular membrane-bounded organelle TAS3460094

    CYP3A4 for ontologies           About GeneDecksing



    CYP3A4 Antibody Products: 
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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    HGNC Gene Families: 
    CYP: Cytochrome P450s

    IUPHAR Guide to PHARMACOLOGY protein family classification: CYP3A4 
    CYP3 family

    4 InterPro protein domains:
     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 domains:
    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


    CYP3A4 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    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, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: 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

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004497monooxygenase activity ISS--
    GO:0005496steroid binding IDA15256616
    GO:0005506iron ion binding IDA15256616
    GO:0008395steroid hydroxylase activity IMP18356043
    GO:0009055electron carrier activity IEA--
         
    CYP3A4 for ontologies           About GeneDecksing


    Animal Models:
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       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for CYP3A4 
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    miRNA
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    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 plasmidCYP3A4 3' UTR sequence
    Inhib. RNA
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    GenScript: all cDNA clones in your preferred vector (see all 2): CYP3A4 (NM_001202855)
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    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, 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 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for CYP3A4 About   (see all 38)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Tamoxifen metabolism
    Tamoxifen metabolism0.68
    Estradiol metabolism0.52
    Tamoxifen Pathway, Pharmacokinetics0.68
    Benzodiazepine Pathway, Pharmacokinetics0.38
    2Irinotecan Pathway, Pharmacokinetics
    Irinotecan Pathway, Pharmacokinetics0.69
    Mycophenolic acid Pathway, Pharmacokinetics/Pharmacodynamics0.50
    Irinotecan Pathway0.69
    Taxane Pathway, Pharmacokinetics0.30
    3Codeine and morphine metabolism
    Codeine and morphine metabolism0.89
    Tramadol Pharmacokinetics0.36
    Codeine and Morphine Pathway, Pharmacokinetics0.89
    4Cytochrome P450 - arranged by substrate type
    Cytochrome P450 - arranged by substrate type0.75
    Phase 1 - Functionalization of compounds0.74
    cytochrome P4500.75
    5Acetaminophen metabolism
    Acetaminophen metabolism0.43
    2-Naphthylamine and 2-Nitronaphtalene metabolism0.32
    Acetaminophen Pathway, Pharmacokinetics0.43

    Pathways by source                                                                                                                                                                 See SuperPaths
    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)
        cytochrome P450
    Aflatoxin B1 metabolism
    Codeine and morphine metabolism
    Irinotecan Pathway
    Tamoxifen 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

    5/9         Kegg Pathways  (Kegg details for CYP3A4) (see all 9):
        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 CentralTM 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)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    AMFRQ9UKV53, ENSP000002906494I2D: score=1 STRING: ENSP00000290649
    STUB1Q9UNE73, ENSP000002195484I2D: score=1 STRING: ENSP00000219548
    UGT2B7P166623, ENSP000003048114I2D: score=1 STRING: ENSP00000304811
    BYSLQ138953I2D: score=5 
    C9orf64Q5T6V53I2D: score=5 
    About this table

    Gene Ontology (GO): 5/16 biological process terms (GO ID links to tree view) (see all 16):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006629lipid metabolic process TAS2492107
    GO:0006706steroid catabolic process IMP18356043
    GO:0006805xenobiotic metabolic process TAS--
    GO:0008202steroid metabolic process IMP3259858
    GO:0008209androgen metabolic process TAS19651758

    CYP3A4 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, 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
    CompoundAction CAS #
    PF 4981517Selective CYP3A4 inhibitor[1390637-82-7]
    MethoxyresorufinFluorometric CYP450 substrate[5725-89-3]
    Letrozole Potent, reversible non-steroidal aromatase inhibitor [112809-51-5]
    ExemestaneSteroidal aromatase (CYP19) inhibitor[107868-30-4]
    PentoxyresorufinFluorometric cytochrome P450 substrate[87687-03-4]

    10/67 HMDB Compounds for CYP3A4 (see all 67)    About this table
    CompoundSynonyms CAS #PubMed Ids
    11,12,15-THETA11,12,15-Trihydroxyicosatrienoic acid (see all 5)----
    11,12-Epoxyeicosatrienoic acid10-(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-EETA14,15-Ep-11-HETrE (see all 11)219535-29-2--
    12,13-EpOMEVernolic acid (see all 12)----
    13-HETE13-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-EETA15-Hydroxy-11,12-epoxyeicosatrienoic acid (see all 9)877878-78-9--
    16(R)-HETE16R-HETE (see all 4)----

    10/535 DrugBank Compounds for CYP3A4 (see all 535)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Clopidogrel-- 113665-84-2enzymesubstrate15679472 15604326 19934256 14707025 12925453 14522569 12485953 19515014
    Astemizole-- 68844-77-9enzymesubstrate inhibitor10597902 11259984 15133245 19934256 12662125 10592235 15684493
    MidazolamDea No. 2884 (see all 4)59467-70-8enzymesubstrate inhibitor12124305 15544435 12065442 9890159 20203109 12433827 19934256
    CerivastatinCerivastatin sodium (see all 2)145599-86-6enzymesubstrate inhibitor inducer17178259 12433802 11523064 9172950 19934256 19515014
    Ifosfamide-- 3778-73-2enzymesubstrate inhibitor inducer16702183 15919850 19934256 19515014 12136253 10348794
    Telithromycin-- 191114-48-4enzymesubstrate inhibitor16199242 15598962 15792396 12149046 11601667 19934256
    AmitriptylineAmitriprolidine (see all 5)50-48-6enzymesubstrate11259560 9131945 18359012 19934256 19515014
    Atorvastatin-- 134523-00-5enzymesubstrate inhibitor inducer17178259 11038166 11523064 19934256 19515014
    Citalopram-- 59729-33-8enzymesubstrate10774624 9890159 19934256 11532381 19515014
    Fluvastatin-- 93957-54-1enzymesubstrate inhibitor inducer11368292 19663817 19934256 10064574 19515014

    10/146 Novoseek inferred 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)

    10/16 PharmGKB related drug/compound annotations for CYP3A4 gene (see all 16)    About this table
    Drug/compound PharmGKB Annotation
    aripiprazole
    clopidogrelCA  
    cyclophosphamideCA  
    docetaxelCA  
    efavirenzCA  
    erythromycinCA  
    fluvoxamine
    gefitinib
    indinavirCA  
    midazolamCA  

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

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, 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, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    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)

    Congresses - knowledge worth sharing:  
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    Additional mRNA 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 

    20 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.313245  DT.448158  DT.95370347 

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

    BG193807 AV650252 BG194899 BG206682 CB164407 CB156859 CB142748 AV657487 
    BG203510 AV650685 CB157599 AV650508 CB161761 AV660672 CB157183 AV647128 
    BC069418 AV650720 AV657708 NM_017460 BG194898 AV652769 AV647783 AV646878 

    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)      CYP3A4 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    CYP3A4 Expression
    About this image


    CYP3A4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/4 selected tissues (see all 4) fully expand
     
     Liver (Hepatobiliary System)    fully expand to see all 5 entries
             Mature Hepatocytes Liver Lobule
             Adult liver progenitor cells
             Hepatocyte-like cells ( Functional hepatocyte generation from human embryonic stem...
     
     Intestine (Gastrointestinal Tract)    fully expand to see all 4 entries
             small intestine ; glandular cells   
             small intestine   
     
     Colon (Gastrointestinal Tract)    fully expand to see all 2 entries
             colon ; glandular cells   
             colonic mucosa   
     
     Amnion (Extraembryonic Tissues)
             Amniotic Epithelial Cells Amniotic Membrane

    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: 
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              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 8/18 species (see all 18)    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 --
    --
    (see all 4)
    --
    63(a)
    60(a)
    (see all 4)
    possible ortholog
    many ↔ many
    (see all 4)
    GL343987.1(68581-71922)
    GL343591.1(16157-77793)
    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 
            Species with no ortholog for CYP3A4

    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  TBXAS12  CYP4F32  CYP4F22  CYP4F112  CYP3A432  CYP4A222  CYP3A72  
    CYP4V22  CYP4B12  CYP3A52  CYP4A112  CYP4Z12  CYP4F122  CYP4X12  
    14 SIMAP similar genes for CYP3A4 using alignment to 5 protein entries:     CP3A4_HUMAN (see all proteins):
    CYP3A43/CYP3A4    CYP3A5    CYP3A7    CYP3A43    CYP4A11    CYP4B1
    thromboxane synthase    TBXAS1    CYP2E1    CYP4V2    CYP19A1    CYP1A1
    CYP2C9    CYP4F12

    CYP3A4 for paralogs           About GeneDecksing


    3 Pseudogenes.org Pseudogenes for CYP3A4
    PGOHUM00000232935 PGOHUM00000263172 PGOHUM00000232936


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, 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

    10/716 SNPs in CYP3A4 are shown (see all 716)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 7 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0116024
    ----see VAR_0116022 V I mis40--------
    VAR_0116004
    ----see VAR_0116002 R Q mis40--------
    rs1114051391,2
    C,F--98731737(+) ATTCCG/AGGTCA 2 -- int12Minor allele frequency- A:0.50NA CSA 4
    rs289885831,2
    C,F--99366709(-) CATTAT/CATTTT 2 -- int18Minor allele frequency- C:0.04NS CSA WA 310
    rs133120801,2
    --99366717(+) ATGACA/CAATAA 2 -- int10--------
    rs133120281,2
    --99366721(+) CCAATA/GATGTC 2 -- int10--------
    rs133124421,2
    --99366792(+) ATCCCC/TGGTCT 2 -- int10--------
    rs133121681,2
    --99366793(+) TCCCTG/TGTCTG 2 -- int10--------
    rs133120441,2
    --99366808(+) GGACAA/GACTCA 2 -- int10--------
    rs133120461,2
    --99366809(+) GACAAA/GCTCAG 2 -- int10--------

    HapMap Linkage Disequilibrium report for CYP3A4 (99354583 - 99381888 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 2 variations for CYP3A4:    About this table     
    Variant IDTypeSubtypePubMed ID
    nsv888771CNV Loss21882294
    nsv482109CNV Gain20164927


    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, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 124010    OMIM disorders: --

    20/122 diseases for CYP3A4 (see all 122):    About MalaCards
    cytochrome p450    xanthomatosis    serotonin syndrome    cerebrotendinous xanthomatosis
    gastroesophageal reflux disease    proctitis    leukopenia    germ cell cancer
    hepatocellular adenoma    antley-bixler syndrome    hiv/aids    osteomalacia
    intrahepatic cholestasis of pregnancy    cholestasis    gilbert syndrome    21-hydroxylase deficiency
    fascioliasis    anxiety disorder    gynecomastia    intrahepatic cholestasis

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

    CYP3A4 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:  
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    10/89 Novoseek inferred 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 2267):
    (articles sorted by number of sources associating them with CYP3A4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. 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)
    2. 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)
    3. Novel mutations of CYP3A4 in Chinese. (PubMed id 11181494)1, 2, 4 Hsieh K.-P.... Huang J.-D. (2001)
    4. Genetic predictors of interindividual variability in hepatic CYP3A4 expression. (PubMed id 19934400)1, 4, 9 Lamba V....Schuetz E.G. (2010)
    5. 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)
    6. 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)
    7. Impact of CYP3A4 haplotypes on irinotecan pharmacokinetics in Japanese cancer patients. (PubMed id 17992531)1, 4, 9 Sai K....Sawada J. (2008)
    8. A CYP3A4 phenotype-based dosing algorithm for individ ualized treatment of irinotecan. (PubMed id 20068078)1, 4, 9 van der Bol J.M....de Jong F.A. (2010)
    9. Genetic variability in CYP3A4 and CYP3A5 in primary liver, gastric and colorectal cancer patients. (PubMed id 17605821)1, 4, 9 Gervasini G....Agundez J.A. (2007)
    10. Systematic screening for polymorphisms in the CYP3A4 gene in the Chinese population. (PubMed id 16981844)1, 4, 9 Du J....He L. (2006)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    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
    NameDescription
    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 Committeehttp://www.cypalleles.ki.se/cyp3a4.htm
    Wikipedia http://en.wikipedia.org/wiki/CYP3A4

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    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



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Sirion Biotech, Cell lines from GenScript, and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
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    GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 4 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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    (GIFtS: 73)
    transforming growth factor, beta 1
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