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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]
CYP3A4 (Cytochrome P450 Family 3 Subfamily A Member 4) is a Protein Coding gene. Diseases associated with CYP3A4 include Acetaminophen Metabolism and Drug Allergy. Among its related pathways are Zidovudine Pathway, Pharmacokinetics/Pharmacodynamics and Cytochrome P450 - arranged by substrate type. Gene Ontology (GO) annotations related to this gene include enzyme binding and iron ion binding. An important paralog of this gene is CYP3A7.
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.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH07J099783 | Promoter/Enhancer | 0.9 | EPDnew ENCODE dbSUPER | 600.7 | -0.2 | -195 | 2 | SP1 RXRA REST TAF1 | CYP3A4 ATP5MF PVRIG piR-39341-368 CYP3A43 RF00017-6476 | |
GH07J099782 | Enhancer | 0.6 | Ensembl | 600.7 | +1.7 | 1747 | 0.6 | GATAD2A RXRB REST SOX13 CTBP1 DPF2 RXRA RARA THRB RAD21 | CYP3A4 piR-61514-175 CYP3A7 CYP3A7-CYP3A51P RF00017-6476 | |
GH07J099797 | Promoter | 0.3 | EPDnew | 600.4 | -13.0 | -12976 | 0.1 | CYP3A4 piR-39341-368 CYP3A43 RF00017-6476 | ||
GH07J099692 | Enhancer | 1.4 | FANTOM5 ENCODE dbSUPER | 2.1 | +90.0 | 89999 | 2.7 | GATAD2A REST TFE3 ZNF512 RFX1 LEF1 IKZF1 NFKBIZ ZNF692 NFRKB | PDAP1 PTCD1 MAP11 CYP3A5 SAP25 ZSCAN25 TMEM225B CYP3A43 CYP3A4 AZGP1 | |
GH07J099791 | Enhancer | 1.2 | FANTOM5 Ensembl ENCODE dbSUPER | 0.4 | -7.9 | -7929 | 3.6 | ATF7 REST IKZF1 ZNF7 SP1 CEBPA CEBPB MGA FOXA2 ATF3 | TRIM4 SAP25 CYP3A43 CYP3A5 CYP3A4 piR-39341-368 RF00017-6476 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004497 | monooxygenase activity | IEA,ISS | -- |
GO:0005496 | steroid binding | IDA | 15256616 |
GO:0005506 | iron ion binding | IEA,IDA | 15256616 |
GO:0005515 | protein binding | IPI | 26988023 |
GO:0008395 | steroid hydroxylase activity | IMP | 18356043 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005737 | cytoplasm | IDA | 18446064 |
GO:0005783 | endoplasmic reticulum | IEA | -- |
GO:0005789 | endoplasmic reticulum membrane | TAS | -- |
GO:0016020 | membrane | IEA | -- |
GO:0016021 | integral component of membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Drug metabolism - cytochrome P450 |
Retinol metabolism
.31
|
Benzo[a]pyrene metabolism
.01
|
2 | Imipramine/Desipramine Pathway, Pharmacokinetics | ||
3 | Cytochrome P450 - arranged by substrate type |
.39
|
Estradiol metabolism
.01
Vitamin D2 (ergocalciferol) metabolism
.01
|
4 | Carvedilol Pathway, Pharmacokinetics | ||
5 | Statin Pathway - Generalized, Pharmacokinetics |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0002933 | lipid hydroxylation | IDA | 14559847 |
GO:0006629 | lipid metabolic process | TAS | 2492107 |
GO:0006631 | fatty acid metabolic process | IEA | -- |
GO:0006694 | steroid biosynthetic process | IEA | -- |
GO:0006706 | steroid catabolic process | IMP | 18356043 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Ketoconazole | Approved, Investigational | Pharma | Pore Blocker, Enzyme, substrate, inhibitor | Inhibitor of cyclosporine oxidase and testosterone 6 beta-hydroxylase, Cytochrome P450c17 inhibitor | 194 | |
Carbamazepine | Approved, Investigational | Pharma | Enzyme, substrate, inducer | Inhibitor of neuronal voltage-gated Na+ channels; anticonvulsant | 104 | |
Clarithromycin | Approved | Pharma | Enzyme, substrate, inhibitor | 379 | ||
Clopidogrel | Approved | Pharma | Enzyme, substrate | P2Y12 receptor antagonist | 934 | |
Midazolam | Approved, Illicit | Pharma | Enzyme, substrate, inhibitor | 1043 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
3-Hydroxyquinine |
|
53467-23-5 | ||||
Paraxanthine |
|
611-59-6 | ||||
11,12,15-THETA |
|
|
||||
11,12-EpETrE |
|
81276-02-0 |
|
|||
11,14,15-THETA |
|
|
Compound | Action | Cas Number |
---|---|---|
Anastrozole | Potent aromatase (CYP19) inhibitor | 120511-73-1 |
Exemestane | Steroidal aromatase (CYP19) inhibitor | 107868-30-4 |
Ketoconazole | Cytochrome P450c17 inhibitor | 65277-42-1 |
TMS | Cytochrome P450 1B1 inhibitor | 24144-92-1 |
YM 511 | Potent aromatase (CYP19) inhibitor | 148869-05-0 |
Compound | Action | Cas Number |
---|---|---|
(+)-Ketoconazole | 142128-59-4 | |
8-Methoxypsoralen | CYP inhibitor | 298-81-7 |
ABT | 1614-12-6 | |
Alizarin | Biological stain | 72-48-0 |
Amiodarone HCl | Anti-arrhythmic drug | 19774-82-4 |
Clarithromycin | 81103-11-9 | |
Cobicistat (GS-9350) | Selective CYP3A inhibitor | 1004316-88-4 |
Ketoconazole | Inhibitor of cyclosporine oxidase and testosterone 6 beta-hydroxylase | 65277-42-1 |
Pentoxyresorufin | 87687-03-4 | |
PF-4981517 | CYP3A4 inhibitor,potent and selective | 1390637-82-7 |
Posaconazole | Sterol C14ɑ demethylase inhibitor | 171228-49-2 |
Posaconazole hydrate | C14ɑ demethylase inhibitor | 1198769-38-8 |
TMS | 24144-92-1 | |
YM 511 | 148869-05-0 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | CYP3A4 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | CYP3A4 30 |
|
||
CYP3A12 31 |
|
ManyToMany | |||
CYP3A26 31 |
|
ManyToMany | |||
-- 31 |
|
ManyToMany | |||
-- 31 |
|
ManyToMany | |||
Cow (Bos Taurus) |
Mammalia | CYP3A5 30 31 31 |
|
ManyToMany | |
-- 31 |
|
ManyToMany | |||
Rat (Rattus norvegicus) |
Mammalia | Cyp3a2 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Cyp3a13 31 |
|
ManyToMany | |
Cyp3a11 31 |
|
ManyToMany | |||
Cyp3a25 31 |
|
ManyToMany | |||
Cyp3a41a 31 |
|
ManyToMany | |||
Cyp3a41b 31 |
|
ManyToMany | |||
Cyp3a16 31 |
|
ManyToMany | |||
Cyp3a44 31 |
|
ManyToMany | |||
Cyp3a59 31 |
|
ManyToMany | |||
Cyp3a57 31 |
|
ManyToMany | |||
Oppossum (Monodelphis domestica) |
Mammalia | -- 31 |
|
ManyToMany | |
-- 31 |
|
ManyToMany | |||
-- 31 |
|
ManyToMany | |||
-- 31 |
|
ManyToMany | |||
Platypus (Ornithorhynchus anatinus) |
Mammalia | -- 31 |
|
ManyToMany | |
-- 31 |
|
ManyToMany | |||
-- 31 |
|
ManyToMany | |||
Chicken (Gallus gallus) |
Aves | CYP3A4 30 |
|
||
CYP3A37 31 |
|
OneToMany | |||
Lizard (Anolis carolinensis) |
Reptilia | -- 31 |
|
ManyToMany | |
-- 31 |
|
ManyToMany | |||
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | LOC100487054 30 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | MGC68821 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | cyp3a65 31 |
|
ManyToMany | |
cyp3c1l2 31 |
|
ManyToMany | |||
si:dkey-21n8.3 31 |
|
ManyToMany | |||
cyp3c1 31 |
|
ManyToMany | |||
cyp3c4 31 |
|
ManyToMany | |||
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.6641 30 |
|
||
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP012293 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | Cyp9f2 30 32 |
|
||
Cyp6a23 32 |
|
|
|||
Cyp6a17 32 |
|
|
|||
Cyp6a14 32 |
|
|
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Cyp6d4 32 |
|
|
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Cyp6g1 32 |
|
|
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Cyp6a13 32 |
|
|
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Cyp6a2 32 |
|
|
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Cyp6a22 32 |
|
|
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Cyp6v1 32 |
|
|
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Cyp9b2 32 |
|
|
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Cyp6a18 32 |
|
|
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Cyp6a19 32 |
|
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Cyp6a20 32 |
|
|
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Cyp6a9 32 |
|
|
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Cyp6d5 32 |
|
|
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Cyp9c1 32 |
|
|
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Cyp28d2 32 |
|
|
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Cyp6a21 32 |
|
|
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Cyp6a8 32 |
|
|
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Cyp6g2 32 |
|
|
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Cyp6w1 32 |
|
|
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Cyp9h1 32 |
|
|
|||
Cyp6d2 32 |
|
|
|||
Cyp28d1 32 |
|
|
|||
Cyp313a1 32 |
|
|
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Cyp6t3 32 |
|
|
|||
Cyp9b1 32 |
|
|
|||
Cyp6t1 32 |
|
|
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Cyp6u1 32 |
|
|
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Cyp28c1 32 |
|
|
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Cyp309a2 32 |
|
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Cyp313a2 32 |
|
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Cyp28a5 32 |
|
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Cyp309a1 32 |
|
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Cyp317a1 32 |
|
|
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Worm (Caenorhabditis elegans) |
Secernentea | cyp-25A1 30 |
|
||
F14F7.3 32 |
|
|
|||
C36A4.1 32 |
|
|
|||
F14F7.2 32 |
|
|
|||
C36A4.2 32 |
|
|
|||
T10B9.1 32 |
|
|
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T10B9.2 32 |
|
|
|||
T10B9.5 32 |
|
|
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T10B9.7 32 |
|
|
|||
T10B9.3 32 |
|
|
|||
T10B9.8 32 |
|
|
|||
C36A4.6 32 |
|
|
|||
F42A6.4 32 |
|
|
|||
ZK1320.4 32 |
|
|
|||
K06G5.2 32 |
|
|
SNP ID | Clinical significance and condition | Chr 07 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
670902 | Likely Benign: not provided | 99,762,206(-) | G/A | MISSENSE_VARIANT | |
768183 | Benign: not provided | 99,768,445(-) | G/A | SYNONYMOUS_VARIANT | |
774657 | Benign: not provided | 99,762,032(-) | G/A | INTRON_VARIANT | |
rs2740574 | Drug Response: CYP3A4 PROMOTER POLYMORPHISM; Cyp3a4-v; tacrolimus response - Dosage | 99,784,473(-) | C/T | ||
rs765598920 | Uncertain Significance: not specified | 99,758,182(-) | G/T | MISSENSE_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
acetaminophen metabolism |
|
|
drug allergy |
|
|
diarrhea |
|
|
anxiety |
|
|
rhinitis |
|
|