Gene:
NR1I2
nuclear receptor subfamily 1, group I, member 2

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB contains no drug labels with pharmacogenomic information for this . To report a drug label with PGx, click here.

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Related Drugs?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
VIP No Clinical Annotations available No Variant Annotations available
rs12721608 119530419G>A, 26025565G>A, 36089G>A, 365G>A, 4321G>A, 482G>A, Arg122Gln, Arg161Gln, NR1I2: PXR*4, R122Q
G > A
Missense
Arg161Gln
No VIP available No Clinical Annotations available VA
rs12721613 119526176C>T, 196C>T, 26021322C>T, 31846C>T, 79C>T, P27S, Pro27Ser, Pro66Ser, g.79C>T
C > T
Missense
Pro66Ser
No VIP available No Clinical Annotations available VA
rs1464602 119526372G>A, 197+78G>A, 26021518G>A, 314+78G>A, 32042G>A, g.275A>G
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs1464603 119526349G>A, 197+55G>A, 26021495G>A, 314+55G>A, 32019G>A, g.252A>G
G > A
Intronic
No VIP available CA VA
rs1523130 -1663T>C, 119499507T>C, 25994653T>C, 5177T>C
T > C
5' UTR
No VIP available No Clinical Annotations available VA
rs2276707 1055-17C>G, 1055-17C>T, 119534153C>G, 119534153C>T, 26029299C>G, 26029299C>T, 39823C>G, 39823C>T, 827-17C>G, 827-17C>T, 938-17C>G, 938-17C>T
C > G
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs2461817 -22-1425A>C, 119524651A>C, 26019797A>C, 30321A>C, 96-1425A>C
A > C
Intronic
No VIP available CA VA
rs2472677 -22-7659C>T, 119518417C>T, 24087C>T, 26013563C>T, 96-7659C>T, NR1I2:63396C>T, PXR 63396C>T
C > T
Intronic
rs3814055 -1135C>T, -1570C>T, 119500035C>T, 25995181C>T, 5705C>T
C > T
5' Flanking
No VIP available No Clinical Annotations available VA
rs3814058 *1232T>C, 119537291T>C, 26032437T>C, 42961T>C
T > C
3' UTR
No VIP available No Clinical Annotations available VA
rs3842689 -205_-200delGAGAAG, -23+253_-23+258delGAGAAG, 119501400_119501405delGAGAAG, 25996546_25996551delGAGAAG, 7070_7075delGAGAAG
GAGAAG > -
5' Flanking
No VIP available No Clinical Annotations available VA
rs4688040 -22-1985G>T, 119524091G>T, 26019237G>T, 29761G>T, 96-1985G>T
G > T
Intronic
No VIP available No Clinical Annotations available VA
rs72551372 119530472G>A, 26025618G>A, 36142G>A, 418G>A, 535G>A, V140M, Val140Met, Val179Met
G > A
Missense
Val179Met
No VIP available No Clinical Annotations available VA
rs72551374 119530542A>G, 26025688A>G, 36212A>G, 488A>G, 605A>G, Asp163Gly, Asp202Gly, D163G
A > G
Missense
Asp202Gly
No VIP available No Clinical Annotations available VA
rs7643645 -22-579A>G, 119525497A>G, 26020643A>G, 31167A>G, 96-579A>G
A > G
Intronic
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  orphan nuclear receptor PXR; pregnane X receptor
Alternate Symbols:  BXR; ONR1; PAR2; PXR; SXR
PharmGKB Accession Id: PA378

Details

Cytogenetic Location: chr3 : q13.33 - q13.33
GP mRNA Boundary: chr3 : 119499331 - 119537332
GP Gene Boundary: chr3 : 119489331 - 119540332
Strand: plus
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

Overview
The NR1I2 gene codes for the pregnane X receptor (PXR) - also referred to as pregnane activating receptor (PAR) and steroid xenobiotic receptor (SXR) ) - a member of the nuclear receptor (NR) superfamily of transcription factors that regulates the induction of many genes. (In this summary, we will use the term NR1I2 to refer to the gene and PXR to refer to the protein encoded by gene.) PXR is a well established regulator of CYP3A4 expression (references listed in Table 1), an enzyme involved in the metabolism of 40-50% of all drugs [Articles:16954191, 9187528] as well as many other genes. The NR1I2 gene maps to chromosome 3q12-13 and has ten exons although only nine form the referemce transcript (see [Article:16101575] Figure 3 for a representation of exons and transcripts and section below, Splice Variants for NR1I2). The reference transcript encodes a protein of 434 amino acids and has the domain structure characteristic of the nuclear receptor superfamily: there is an N-terminus region; a DNA binding domain (DBD), consisting of two zinc fingers (amino acids 41-107); a hinge region (amino acids 107-141) and ligand binding domain (LBD) containing the ligand binding pocket and a ligand-depending activation factor (AF-2) domain (amino acids 141-434) [Articles:16101574, 14657421]. Unique to PXR is an approximately 60 amino acid sequence in the LBD that appears to allow accommodation of a wide variety of ligands; see [Articles:11408620, 15705662] and other references in Structure section below.

A simplified view of the steps in PXR gene regulation is as follows: PXR is activated by a ligand, forms a heterodimer with 9-cis retinoic acid receptor RXRalpha [Articles:9784494, 9727070, 9489701, 11706036], that binds to specific DNA response elements in the target gene [Articles:9784494, 9489701, 11706036, 12372848, 9727070], and induces gene expression. The full story of transcriptional regulation is much more complicated: PXR is constitutively inactive and is generally thought to reside in the nucleus regardless of the presence or absence of its inducers [Articles:11264453, 14709632] (although work by Squires, et al [Article:15347657] in mouse livers, show that PXR is localized in the cytoplasm and translocates to the nucleus upon ligand binding.) Ligand-free PXR is bound to corepressors NCOR1 [Article:11329060] and NCOR2 (also known as the silencing mediator of retinoid and thyroid hormone receptor; SMRT) [Articles:11329060, 16219912]; ligand binding causes dissociation of this complex [Article:16219912]. Ligand binding and PXR activation of gene transcription also involves recruitment of other proteins, in particular, the Steroid receptor coactivator 1 (SRC-1, NCOA1) [Articles:16455805, 9727070, 15650019, 17998298], but other proteins are also involved, including PGC-1 (PPRC1) [Article:16455805] and Hepatic Nuclear Factor 4 alpha (HNF4A), another NR [Articles:16455805, 12514743, 20086032] and protein arginine methyltransferase 1 (PRMT1) another co-activator [Article:19144646].

Expression of NR1I2 itself is regulated by other NRs, including the glucocorticoid receptor (GR, NR3C1) [Articles:10908304, 12511605, 16718615], HNF4A [Article:17827783], farnesoid X receptor (FXR), NR1H4) [Article:16682417] and FOXA2 [Article:19934400]. Expression of NR1I2 is repressed by interleukin-6 [Article:10924340], small heterodimer partner, (SHP, NR0B2), another NR [Articles:12805410, 16455805], NF-kb p65 (RELA) [Article:16608838] and protein kinase c alpha (PRKCA) [Article:15710363]; consequently repression of PXR-mediated CYP3A4 induction occurs.

Gene Targets
PXR, like other NRs, regulates transcription of many genes, in particular those genes that metabolize and transport drugs. The most-studied PXR gene target is CYP3A4 (see Table 1 for list of references). Other gene targets listed in Table 1 and identified via functional assays include ABCB1 [Articles:11329060, 20041327, 11297522], ABCC2 [Articles:11466304, 11706036], ABCC3 [Article:11323161], ALAS1 [Article:12181440], AHR [Article:12181440], ALDH1A1 [Article:12181440], CYP1A1 [Articles:12181440, 19326768], CYP1A2 [Articles:12181440, 10820139], CYP2A6 [Articles:12181440, 19326768], CYP2B6 [Articles:16718615, 12181440, 11560876, 18096673, 19326768, 15761118, 19520773, 9157990, 10820139], CYP2C8 [Articles:12181440, 11329060, 9157990], CYP2C9 [Articles:16718615, 12181440, 11560876, 18096673, 19369937, 17513950, 11466304, 9157990, 11714868, 14600250], CYP3A5 [Articles:18725505, 15252010], GSTA2 [Article:12181440], POR [Article:12181440], SULT1A1 [Article:12181440]. Additionally, PXR DNA binding elements have been found in other genes, via in silico analysis, then verified experimentally; these genes are UGT1A6] [Article:15316010], UGT1A3 [Articles:15316010, 15077869], UGT1A4 [Article:15077869], CASP10 [Article:15316010]. Microarray experiments [Article:11714868] with rifampin identified other genes presumed to be PXR targets: CYP2A6, CYP3A7, CYP4F3, CYP1B1, GSTA1, GSTA3, SLC22A5, TTR, MAOB, FMO4, FMO5, GSTA2, GSTM1, GSTP1. There are conflicting data about UGT1A1 [Articles:15077869, 16718615, 12181440, 15316010], CYP1A2 [Articles:11714868, 12181440], CYP2E1 [Articles:11714868, 12181440].

In addition to transactivation of genes, PXR is also involved with inhibition/repression: Rifampin-liganded PXR suppresses SULT2A1 expression by interfering with HNF4A activity [Article:17687072]; PXR inhibits CYP7A1 gene transcription [Article:15331348]; activation of PXR by rifampin and other agonists inhibits NF-kB signaling [Article:16841097]. PXR is also involved in regulation of CYP4F12 that does not involve rifampin [Article:19129222].

Drugs/Substrates:
Originally an orphan receptor, PXR was found first to respond to endogenous pregnanes, which gave rise to its name, but was subsequently shown to be activated by other endogenous ligands, as well as a wide variety of xenobiotics, including clinical drugs [Articles:9770465, 9784494, 9489701, 9727070].

The list of reported PXR agonists - and inducers of gene transcription - is enormous; it has been the subject of many in vitro studies because of the need to identify potential drug-drug interactions resulting from induction of metabolizing enzymes. However, an accurate compilation of hPXR ligands is difficult for several reasons:
(1) In testing for PXR ligands, the increase in CYP3A4 (or other target gene) mRNA is often measured. But, as is the case for CYP3A4, gene expression is regulated by several different NRs, besides PXR, such as the Constituitively Androgen Receptor (CAR, NR1I3), GR, HNF4A, FXR and the Vitamin D Receptor (VDR)[Article:17442683]. Therefore, the actual NR responsible for the induction may not always be certain; i.e., the ligand may be binding to a NR other than PXR that is responsible for the induction and increase in mRNA [Article:17442683].
(2) A molecule may have an effect via an indirect interaction with PXR. Some ligands bind not only to PXR, but also to other NRs that are involved with PXR regulation. For example, dexamethasone has been reported as a ligand for PXR [Articles:9727070, 12065438], but it is also a ligand for GR [Article:12151000] and GR is associated with regulation of NR1I2 [Articles:10908304, 12511605, 16718615].
(3) Human, rabbit, and rodent PXRs display marked differences in response to different xenobiotics [Articles:10935643, 10628745, 11336976, 9727070], so care must be taken to identify only hPXR ligands. For example, hPXR responds to rifampin, but rat PXR does not; in contrast, rodent PXR responds to pregnenolone-16a-carbonitrile (PCN), but hPXR does not [Articles:10935643, 10628745, 11336976]. This difference is related to the difference in the amino acid composition of the LBD: While the DBD is very similar across species, the LBDs of the PXRs are very different [Article:12372848]; the human and rat PXR share only 76% amino acid identity in their LBD [Article:12372848].

For the reason described above, we therefore list in Table 1 below, those ligands where the researcher his/herself declared them to be "hPXR ligands/activators". We also report conflicting data, where available, that might dispute this. Note that the classic PXR agonist is rifampin.

All agonists listed in Table 1 were identified via functional cell-based assays. Where there is also in vivo clinical data for a ligand, such data is included; this may be consistent or inconsistent with the induction of the target gene. The vast majority of the drugs listed do not have such clinical data. (The exceptions are rifampin, ifosfamide, st. john's wort (hyperforin), efavirenz, carbamazepine and phenytoin, where there are several in vivo human studies consistent with the increased CYP3A4 metabolism; although, for the latter 3 drugs, there is data to suggest that these are hCAR ligands, rather than hPXR ligands [Articles:17041008, 15123723, 17041008]). While it might be tempting to assume that an in vitro PXR agonist is actually an in vivo inducer of a gene such CYP3A4, such extrapolation can be dangerous. There are other, competing ligand-protein interactions in the body so the net systemic effect of a PXR ligand may not be clear cut. The competing interactions:
(1) The intracellular concentration of the agonist is mediated by a transporter that controls its efflux or influx, when it is also a substrate for the transporter; Schuetz et al. [Article:8633005] demonstrated that ABCB1 modulates the extent of CYP3A induction through regulating intracellular concentration of rifampin.
(2) As described by Tang, et al, [Article:15673596] a PXR ligand can be metabolized at different rates, depending upon an individual's metabolic phenotype; the induction in such individuals would thus be different. For example, omeprazole [Articles:16413245, 16093273] and mephenytoin [Articles:19661214, 8110777] are metabolized by CYP2C19; genetic polymorphisms in this gene results in individuals being "extensive metaboizers" (EM), or "poor metaboizers" (PM) of these drugs - the individual's metabolic phenotype [Article:12222994]. While omeprazole has been shown, in vitro, to be an inducer of CYP1A [Articles:8169844, 11336975], in in vivo studies, therapeutic doses of omeprazole induces CYP1A2 metabolism of S-mephenytoin in PM, but have only minor effects in EM [Article:1505152]. On the other hand, Zhou et al. [Article:2223426] found that induction by rifampin of the metabolism of mephenytoin was only observed with EMs, but not with PMs.
(3) The PXR ligands themselves interact with other proteins, other than PXR, with the result that these other interaction dominates. A good example of this is ketoconazole: it has been reported as an activator of PXR [Article:17998298], but is also a strong inhibitor of CYP3A4 [Articles:19702536, 16954191, 10709776]; as a result, this drug is applied for therapeutic purposes to effectively increase the dosage of another drug, such as cyclosporine [Article:10709776]. (Ketoconazole is not listed in the table because of its clinically large inhibitory effect on CYP3A4).

PXR antagonists are few; they include A-792611 [Article:18096673], sulforaphane (molecule present in broccoli) [Articles:18725505, 17028159], ecteinascidin-743 [Article:11329060].

Phenotypes/Diseases:
Besides regulating many xenobiotic metabolizing enzymes and transporters, PXR also plays a role in cholesterol homeostasis [Article:11607932] and bile acid metabolism [Articles:11248085, 11509573]. Its involvement has been implicated in resistance to some cancers [Articles:17636047, 17279585, 17974979, 18765524] as well as, Inflammatory Bowel Diseases (IBD), Crohn's disease (CD), and ulcerative colitis (UC) [Articles:16472590, 17828778].

Structural Data
The crystal structure of the LBD of hPXR was first solved in 2001 [Article:11408620]; as of May 1010, there are 9 crystal structures of the LBD of hPXR in the Protein Data Bank [Article:10592235]. We briefly list the structures here: 1ILG (apo structure, resolution=2.52 A) [Article:11408620]; 1ILH (bound to SR12813, resolution=2.76 A) [Article:11408620]; 1M13 (bound to hyperforin, resolution=2.15 A) [Article:12578355]; 1NRL (bound to SR12813 and peptide from SRC-1 co-activator, resolution=2.0 A) [Article:12909012]; 1SKX (bound to rifampin, resolution=2.8 A) [Article:15705662]; 2O9I (bound to T0901317 and peptide from SRC-1, resolution=2.8 A) [Article:17215127]; 2QNV (bound to colupulone , resolution=2.8 A) not in pubmed; 3CTB (apo structure, tethered to peptide from SRC-1, resolution=2.0 A) [Article:18456871]; 3HVL (bound to SR12813; tethered to peptide from SRC-1 co-activator, resolution=2.1 A) [Article:18456871].

Overall, the crystal structures show how a diverse group of ligands can be bound to the same protein. The binding cavity is substantially larger than that of other NRs [Article:11408620]; in 1ILH, SR12813 is found in 3 distinct, different binding modes [Article:11408620]. In the structure of rifampin and hyperforin, several regions near the protein binding pocket are disordered, suggesting that there is a large degree of protein flexibility that is used to effectively enlarge to ligand binding pocket [Articles:15705662, 12578355].

Splice Variants:
There are many isoforms of PXR due to alternative splicing [Articles:10473093, 15364541, 12413960, 15364541, 12413960] or defective splicing [Article:12413960]. The reference transcript (PXR.1) encoded by 9 exons contains 434 amino acids [Article:11668216]; alternatively spliced forms (PXR.2, PXR.3) arise from a deletion of 37 or 41 amino acids from exon 5 [Articles:10473093, 15364541]; the deletion of 238 bp from 5' end of exon 5 leads to a truncated amino acid sequence [Article:15364541]. There are several other splice forms, some of which encoded all 10 exons [Article:12413960]. (For a list of alternative splice forms, see Uniprot AccessionID=O75469)

Pharmacogenomics:
As of May 2010, there are 256 human SNPs deposited in dbSNP build 131 [Article:11125122]. Approximately half of these variants were studied using cell-based or tissue-based functional assays [Articles:11602521, 11668216, 12663745, 14586772, 14709632, 15618712, 15864135, 16568343, 16580901, 17050801, 17876342, 17924830, 17925385, 18056193, 18220558, 18294295, 18800312, 18981011, 19173680, 19855097, 19940802, 20082578, 20107201]. Very few variants have been characterized functionally (and clinically) by more than one study. The interpretation and clinical impact of these cell-based and tissue-based studies is difficult for several reasons:
(1) Many of the variants were associated with altered CYP3A4 basal metabolism, but because PXR is not constituitively active and the endogenous ligand was not identified, the actual mechanism of altered basal CYP3A4 metabolism is not clear.
(2) CYP3A4 expression in liver samples is significantly higher in females than in males [Article:19934400] independent of NR1I2 genotype; there can be a need to segregate fold-induction based upon sex [Article:17925385]; which is not always done.
(3) Variants with a lower CYP3A4 basal metabolism often show a greater drug-induced-fold induction [Article:17925385], so the net clinical overall effect with respect to potential drug-drug interactions can be difficult to predict. For these reasons, for this summary, we briefly describe a handful of the functional-based studies, organized by the studies themselves, and concentrate on those studies where larger numbers of variants were studied. We separately describe clinical studies, organized in the same manner. The one variant that has been examined by several different groups is described last and separately. Overall, the contribution of genetic variants of NR1I2 to the large variability in human drug response is unclear.

Zhang, et al, [Article:11668216], in vitro studies (and in vivo studies, described below), identified 38 SNPs in NR1I2 several (but not all) were correlated with increased fold-induction of CYP3A4, and others with lower levels of ABCB1 induction and one variant rs12721608 (R122Q) had significantly decreased affinity for the DNA binding sequence. Hustert, et al [Article:11602521] studied 6 genotypic variants and splice variants and found that variant D163G rs72551374 and splice variant PXR-2 (lacking 37 amino acids in the LBD) did not show any basal activity; however, the allelic frequencies of these variants are a minuscule fraction of the populations studied. Lambda, et al [Article:17925385] identified 89 SNPs in the promoter region and intron 1, many in linkage disequilibrium; 5 variants were consistently associated with altered basal or inducible metabolism. Finally, Koyano et al [Article:14709632] found 4 variants, 3 of which had reduced transactivation of CYP3A4; one of these, rs72551371 (R98C), had a dramatic reduction in DNA binding.

Fewer NR1I2 variants have been studied clinically; many of these studies are of small size and a few do not show a correlation between genotype and pharmacokinetics. Zhang, et al, [Article:11668216] in the study of 14 patients, found that those carrying \-25385C>T (rs3814055) and \-24113T>A (GenBank Accession AF364606) had a 2 fold higher metabolism of erythromycin, using the erythromycin breath test (ERMBT), following rifampin treatment; biopsies of intestinal samples of 10 patients found higher induction of CYP3A4 following rifampin treatment, for several other patients. He, et al [Article:17050801] in a study of 26 healthy volunteers, identified 3 linked NR1I2 variants (g.252A>G (rs1464603), g.275A>G (rs1464602), and g.4760G>A ; AF364606) significantly (P < .05) associated with oral midazolam clearance in the African American subpopulation (n = 14) but not in European Americans (n = 9). Fanta, et al [Article:20107201], in a study of 91 kidney transplant patients, found that the patients of the (g.\-25385C (rs3814055), g.\-24381A (rs1523127), g.\-205\_\-200GAGAAG (rs72554003), g.7635G (rs6785049), g.8055C) haplotype had about one-tenth lower bioavailability, per allele, than did noncarriers of this haplotype (P = .04). Wang,et al, [Article:19173680] in a study of 10 healthy Han volunteers, found that ingestion of St. John's wort greatly increased nifedipine metabolism of 2 haplotypes. Sandanaraj et al [Article:18981011] studied doxorubicin clearance in 100 Malay, 100 Chinese and 100 Indian breast cancer patients and found that those patients harboring the (rs3814058 and rs2276707) haplotype had significantly lower clearance of doxorubicin compared to patients not carrying this haplotype (P = 0.022). While these clinical studies found an association between phenotype and genotype, others did not. Zhang, et al, [Article:11668216] found that the one person heterozygous for rs12721608 (R122Q) - the variant with significantly decreased DNA binding - had normal cyp3a4 metabolism. And, studies of 95 and 101 breast cancer patients did not find any association between docetaxel clearance and NR1I2 genotype [Articles:17876342, 18056193].

All results remain to be validated.

One variant (rs3814055) (\-25385 C>T, AF364606) has been studied by several researchers, for both disease risk and pharmacogenomics impact, with conflicting results. See Variant Summary for more details.

Table 1. Agonists/ligands of hPXR and target genes. Column 1 lists drugs and molecules identified by functional assays (FA) to be ligands of PXR, organized by class; column 2 lists the target genes that were up-regulated by the drug-bound PXR in the FA (in the case no specific target gene was mentioned, the term PXR activation is used); Column 3 lists references for the FA; Column 4 lists references related to clinical data in support of, or in conflict with, the FA data. In the event there is conflicting data, drug or reference is in italics

DRUGSTARGET GENEREFERENCES (FA/ in vitro)REFERENCES (clinical)
ANTIBACTERIALS,BETA-LACTAM ANTIBACTERIALS, PENICILLINS
amoxicillinCYP3A4[Article:18505790]
ampicillinCYP3A4[Article:18505790]
dicloxacillinCYP3A4[Article:18505790]
nafcillinCYP3A4 [Article:18505790]
penicillin VCYP3A4[Article:18505790]
ANTIBACTERIAL CEPHALOSPORINS
cefaclorCYP3A4[Article:18505790]
cefadroxilCYP3A4[Article:18505790]
cefuroximeCYP3A4[Article:18505790]
cephalexinCYP3A4[Article:18505790]
cefradineCYP3A4[Article:18505790]
ANTIBACTERIAL LINCOSAMIDE
clindamycinCYP3A4[Article:18505790]
ANTIBACTERIAL SULFONAMIDES
sulfamethazineCYP3A4[Articles:12065438, 18505790][Articles:3082414, 6130373]
sulfisoxazoleCYP3A4[Article:18505790]
ANTIBACTERIAL, MACROLIDES
erythromycinCYP3A4[Article:18505790]
troleandomycinCYP3A4[Article:18505790]
troleandomycin PXR activation but NO induction of CYP3A4 activity[Article:12065438]
ANTIBIOTIC (FOR TREATMENT OF TUBERCULOSIS)
rifabutinPXR activation[Articles:16724927, 18647599]
rifampinCYP3A4, ABCB1, ABCC2, ABCC3, ALAS1, AHR, ALDH1A1, CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2E1, GSTA2, POR, SULT1A1, UGT1A1 [Articles:10628745, 9770465, 9727070, 17998298, 16724927, 12065438, 18505790, 10748001, 11329060, 11297522, 19520773, 11706036, 11323161][Articles:11503007, 9157990, 7751591, 12426514, 17381666, 16176119, 6487483, 19417618, 9871429, 9024169, 16580903, 11180018, 11240975, 9542475, 10223773, 19369937, 2223426]
rifapentinePXR activation[Article:16724927]
ANTIBIOTIC/ANTIBACTERIAL TETRACYCLINE
demeclocyclineCYP3A4[Article:18505790]
doxycyclineCYP3A4[Article:18505790]
minocyclineCYP3A4[Article:18505790]
tetracyclineCYP3A4[Article:18505790]
ANTICONVULSANT
topiramateCYP3A4[Article:18505790][Article:9070594]
ANTIEPILEPTICS
carbamazepineCYP3A4[Articles:17112801, 12065438][Articles:2126946, 14691614, 8598183, 10613614]
carbamazepine possible hCAR ligand [Article:17041008]
phenobarbitolALDH1A1, CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP3A4 & GSTA2, ABCB1, SULT1A1, ALAS1, AHR, POR [Articles:12181440, 9727070, 10628745, 12065438, 12642468, 14600250, 15252010, 16724927, 18647599][Articles:7408397, 3392664, 12242602]
phenytoinCYP3A4[Articles:12065438, 16724927, 18647599][Articles:7408397, 2126946, 8598183, 19855097, 4049465, 9485556, 10613614]
phenytoin hCAR ligand [Article:15123723]
valproic acidCYP3A4[Article:17392393][Article:9070594]
[Article:9156377]
ANTIFUNGAL
griseofulvinCYP3A4[Article:18505790]
terbinafineCYP3A4[Article:18647599] [Article:8869684]
ANTIFUNGAL/ANTIMYCOTIC
clotrimazoleCYP3A4, CYP3A5[Articles:10748001, 10628745, 9770465, 9727070, 15252010, 17998298]
econazoleCYP3A4[Article:17998298]
miconazoleCYP3A4[Article:17998298]
oxiconazoleCYP3A4[Article:17998298]
ANTIGOUT PREPARATIONS
sulfinpyrazoneCYP3A4[Articles:12065438, 16724927, 18647599][Article:11124491]
ANTIHYPERTENSIVES
bosentanPXR activation[Articles:12206849, 18669588][Articles:12047483, 12603176]
reserpineCYP3A4[Article:17041008]
ANTIINFLAMMATORY/ANTIRHEUMATIC
phenylbutazonePXR activation[Article:16724927]
ANTIMALARIALS
artemisininCYP2B6, CYP3A4, ABCB1[Article:15761118]
artemisinin hCAR ligand [Articles:16919048, 18332078]
ANTINEOPLASTIC ALKYLATING AGENTS
cyclophosphamideCYP2B6, CYP2C8, CYP2C9, CYP3A4, ABCB1, [Articles:9157990, 17041008, 20041327][Article:3058371]
ifosfamideCYP2B6, CYP2C8, CYP2C9, CYP3A4, ABCB1 [Articles:9157990, 20041327] [Articles:7720176, 17106751, 11503007, 8161344]
[Article:17464949]
ANTINEOPLASTIC PLATINUM COMPOUND
cisplatinCYP3A4, ABCB1[Article:15650019]
ANTINEOPLASTIC TAXANE
docetaxelABCB1[Article:20041327]
docetaxel no PXR activation [Articles:11329060, 15650019]
paclitaxelABCB1,CYP2C8, CYP3A4 [Articles:11329060, 15650019, 20041327]
ANTINEOPLASTIC, OTHER
bexaroteneCYP3A[Article:10628745]
ANTINEOPLASTIC, VINCA ALKALOIDS
vinblastineABCB1[Article:20041327]
vincristineABCB1[Article:20041327]
ANTIPARASITIC
permethrinCYP3A4, CYP1A1, CYP3A5, CYP2B6, CYP2A6[Article:19326768]
ANTIPSYCHOTIC
chlorpromazineCYP3A4[Article:17041008]
BILE ACID
lithocholic acidPXR activation[Article:11248085] (rat)
BLOOD GLUCOSE LOWERING SULFONAMIDE UREA
glibenclamide PXR activation [Article:12206849]
BLOOD GLUCOSE LOWERING THIAZOLIDINEDIONE
troglitazoneCYP3A4[Articles:10628745, 16724927, 17041008][Articles:10197300, 9753209]
rosiglitazoneCYP3A4[Article:12642470]
pioglitazoneCYP3A4[Article:12642470] [Article:12463723]
CALCIUM CHANNEL BLOCKERS
isradipine CYP3A4, CYP2B6 and CYP2C9 [Article:11560876]
nicardipineCYP3A4, CYP2B6, and CYP2C9[Articles:11560876, 17041008]
nifedipineCYP3A4, CYP2B6 and CYP2C9[Articles:11560876, 9784494, 9770465]
HMG COA REDUCTASE INHIBITORS
atorvastatinCYP2C9[Article:17513950]
fluvastatinCYP2C9[Article:17513950]
lovastatinCYP3A4[Articles:9727070, 17513950, 17041008]
mevastatinCYP3A4[Articles:12235278, 17041008]
simvastatinCYP3A4[Article:17041008]
HYDRAZIDES (FOR TREATMENT OF TUBERCULOSIS)
isoniazidCYP2E1[Article:12642468]
NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
efavirenzCYP3A4 [Article:18096673][Articles:1251999, 12189360, 17998298, 19620877, 17041008]
efavirenz possible hCAR ligand [Article:17041008]
nevirapineCYP3A4[Article:17041008][Article:10421616]
nevirapine possible hCAR ligand [Article:17041008]
NUTRACEUTICAL
Ginkgo bilobaABCB1, CYP3A4, CYP3A5[Article:18725505]
guggulipidPXR activation[Article:18768384]
st john's wort (hyperforin)CYP3A4, CYP2C8, ABCB1, ABCC2[Articles:10852961, 11329060, 16724927, 11329060, 10852961, 11706036][Articles:11673747, 14663455, 19924124, 15537555, 10683008]
OPIOD
methadoneCYP2B6, CYP3A4, UGT1A1[Article:19520773]
OTHER PLANT COMPONENT OR EXTRACT
coumestrolPXR activation[Article:9784494]
coumestrol antagonist? [Article:18096694]
forskolin CYP3A [Articles:16724927, 15459237]
colupulone (active ingredient of hops)PXR activation xtl structure[Article:18768384]
PROTEASE INHIBITORS
ritonavirCYP3A4, CYP2B6, CYP2C9, ABCC2[Articles:18096673, 16724927, 12065438, 11466304, 18647599][Article:9723818]
[Article:10801241]
saquinavirPXR activation[Article:11466304]
PROTON PUMP INHIBITORS
lansoprazoleCYP3A, CYP1A[Article:8169844]
omeprazoleCYP3A, CYP3A4, CYP3A5, CYP1A [Articles:11336975, 8169844, 12235278, 15252010, 17041008, 18647599][Article:1505152]
PSYCHOSTIMULANTS
modafinilCYP1A2, CYP2B6, CYP3A4/5[Article:10820139][Article:11823757]
STEROID
pregnenoloneCYP3A4[Articles:9784494, 9727070]
STEROID (CORTICOSTEROID)
budesonideCYP3A4[Article:19138736]
corticosteroneCYP3A[Articles:10628745, 9784494]
hydrocortisone (cortisol)CYP3A4[Article:9770465]
dexamethasoneCYP3A4[Articles:9727070, 12065438][Articles:3058371, 11061575]
STEROID (HORMONE)
17α-HydroxyprogesteroneCYP3A[Article:10628745]
dehydroepiandrosterone (DHEA)PXR activation[Article:9784494]
estradiolCYP3A, CYP3A4[Articles:9770465, 9784494, 10628745]
progesteroneCYP3A4[Articles:9770465, 9727070]
diethylstilbestrol (DES) PXR activation[Article:9784494]
STEROID (HORMONE METABOLITE)
dihydrotestosterone CYP3A [Article:10628745]
STEROID (PREGNANE-RELATED)
5 beta-Pregnane-3,20-dioneCYP3A4[Articles:10748001, 10628745, 9770465, 9727070]
STEROID (ANTIANDROGEN)
cyproteroneCYP3A4[Article:9727070]
flutamideABCB1[Article:20041327]
spironolactoneCYP3A4[Article:9727070]
STEROID (ANTIESTROGEN)
tamoxifenCYP3A4, ABCB1 [Articles:18299335, 20041327] [Articles:11487258, 10499602]
STEROID (ANTIESTROGEN METABOLITE)
4-hydroxytamoxifenCYP3A4[Article:18299335]
STEROID (ANTIPROGESTOGEN)
mifepristone (RU486) CYP3A4 , CYP3A5 [Articles:12235278, 15252010, 16724927, 10748001, 10628745, 9770465, 9727070]
TEST FOR PITUITARY FUNCTION
metyrapone CYP3A4 [Articles:10611146, 17041008, 10917608]
OTHER
SR12813CYP3A4, ABCC2[Articles:11466304, 10628745, 10748001, 11329060, 16724927]

Alphabetical list of abbreviations (that are not gene symbols)
CD=Crohn's disease, DBD=DNA binding domain, EM=extensive metaboizers, ERMBT=erythromycin breath test, FA=functional assay, FXR=farnesoid X receptor, GR=glucocorticoid receptor, IBD=Inflammatory Bowel Diseases, LBD=ligand binding domain, NR=nuclear receptor, PAR=pregnane activating receptor, PM=poor metaboizers, PXR=pregnane X receptor, RXRa=9-cis retinoic acid receptor, SMRT=silencing mediator of retinoid and thyroid hormone receptor, SNP=single nucleotide polymorphism, SRC-1=Steroid receptor coactivator 1, SXR=steroid xenobiotic receptor, UC=ulcerative colitis.

Citation
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
History

Submitted by Connie Oshiro (June 2010)

Variant Summaries rs12721608, rs3814055
Drugs
Drug (82)
amoxicillin, ampicillin, artemisinin, atorvastatin, bexarotene, bosentan, budesonide, carbamazepine, cefaclor, cefadroxil, cefradine, cefuroxime, cephalexin, chlorpromazine, cisplatin, clindamycin, clotrimazole, cyclophosphamide, cyproterone, demeclocycline, dexamethasone, dicloxacillin, diethylstilbestrol, docetaxel, doxycycline, econazole, efavirenz, erythromycin, flutamide, fluvastatin, forskolin, glibenclamide, griseofulvin, hydrocortisone, ifosfamide, isoniazid, isradipine, lansoprazole, lovastatin, methadone, metyrapone, miconazole, minocycline, modafinil, nafcillin, nevirapine, nicardipine, nifedipine, omeprazole, oxiconazole, paclitaxel, penicillin v, permethrin, phenobarbital, phenylbutazone, phenytoin, pioglitazone, progesterone, reserpine, rifabutin, rifampin, rifapentine, ritonavir, rosiglitazone, saquinavir, simvastatin, spironolactone, st. john's wort, sulfamethazine, sulfinpyrazone, sulfisoxazole, tamoxifen, terbinafine, tetracycline, topiramate, troglitazone, troleandomycin, troleandomycin, valproic acid, vinblastine, vincristine, xenobiotics
Diseases

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Carbamazepine Pathway, Pharmacokinetics
    Stylized liver cell depicting candidate genes involved in the pharmacokinetics of carbamazepine.
  1. Etoposide Pathway, Pharmacokinetics/Pharmacodynamics
    Etoposide cellular disposition and effects.
  1. Taxane Pathway, Pharmacokinetics
    Representation of the genes involved in the metabolism and transport of paclitaxel and docetaxel, and the downstream effects of the drugs.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this gene. To report a pathway, click here.

Curated Information ?

Curated Information ?

Evidence Drug Class
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
xenobiotics

Curated Information ?

Publications related to NR1I2: 80

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Pregnane X receptor and hepatocyte nuclear factor 4alpha polymorphisms are cooperatively associated with carbamazepine autoinduction. Pharmacogenetics and genomics. 2013. Saruwatari Junji, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Pharmacogenetic study on risperidone long-acting injection: influence of cytochrome P450 2D6 and pregnane X receptor on risperidone exposure and drug-induced side-effects. Journal of clinical psychopharmacology. 2013. Choong Eva, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Population pharmacokinetic study of memantine: effects of clinical and genetic factors. Clinical pharmacokinetics. 2013. Noetzli Muriel, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Association of carbamazepine major metabolism and transport pathway gene polymorphisms and pharmacokinetics in patients with epilepsy. Pharmacogenomics. 2013. Puranik Yogita Ghodke, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo. Toxicology and applied pharmacology. 2012. Poulton Emma Jane, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Potential effect of pharmacogenetics on maternal, fetal and infant antiretroviral drug exposure during pregnancy and breastfeeding. Pharmacogenomics. 2012. Olagunju Adeniyi, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Human PXR-mediated induction of intestinal CYP3A4 attenuates 1alpha,25-dihydroxyvitamin D₃ function in human colon adenocarcinoma LS180 cells. Biochemical pharmacology. 2012. Zheng Xi Emily, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Exploration of CYP450 and drug transporter genotypes and correlations with nevirapine exposure in Malawians. Pharmacogenomics. 2012. Brown Kevin C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Impact on response and survival of DNA repair single nucleotide polymorphisms in relapsed or refractory multiple myeloma patients treated with thalidomide. Leukemia research. 2011. Cibeira María Teresa, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effects of pregnane X receptor (NR1I2) and CYP2B6 genetic polymorphisms on the induction of bupropion hydroxylation by rifampin. Drug metabolism and disposition: the biological fate of chemicals. 2011. Chung Jae Yong, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Population Pharmacokinetic modelling of the association between 63396C->T Pregnane-X-Receptor (PXR) polymorphism and unboosted atazanavir clearance. Antimicrobial agents and chemotherapy. 2010. Schipani Alessandro, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PXR-mediated induction of P-glycoprotein by anticancer drugs in a human colon adenocarcinoma-derived cell line. Cancer chemotherapy and pharmacology. 2010. Harmsen Stefan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PharmGKB summary: very important pharmacogene information for CYP2B6. Pharmacogenetics and genomics. 2010. Thorn Caroline F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic polymorphisms of CYP1A2, CYP3A4, CYP3A5, pregnane/steroid X receptor and constitutive androstane receptor in 207 healthy Spanish volunteers. Clinical chemistry and laboratory medicine : CCLM / FESCC. 2010. Oliver Paloma, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
A role for the pregnane X receptor in flucloxacillin-induced liver injury. Hepatology (Baltimore, Md.). 2010. Andrews Elise, et al. PubMed
Long-term changes in cyclosporine pharmacokinetics after renal transplantation in children: evidence for saturable presystemic metabolism and effect of NR1I2 polymorphism. Journal of clinical pharmacology. 2010. Fanta Samuel, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic enhancer without anti-HIV activity. Clinical pharmacology and therapeutics. 2010. Mathias A A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP2C9*1B promoter polymorphisms, in linkage with CYP2C19*2, affect phenytoin autoinduction of clearance and maintenance dose. The Journal of pharmacology and experimental therapeutics. 2010. Chaudhry Amarjit S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The nuclear receptor PXR gene variants are associated with liver injury in nonalcoholic fatty liver disease. Pharmacogenetics and genomics. 2010. Sookoian Silvia, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Taxane Pathway. Pharmacogenetics and genomics. 2009. Oshiro Connie, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic polymorphisms in the TATA box and upstream phenobarbital-responsive enhancer module of the UGT1A1 promoter have combined effects on UDP-glucuronosyltransferase 1A1 transcription mediated by constitutive androstane receptor, pregnane X receptor, or glucocorticoid receptor in human liver. Drug metabolism and disposition: the biological fate of chemicals. 2009. Li Ye, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Methadone induces the expression of hepatic drug-metabolizing enzymes through the activation of pregnane X receptor and constitutive androstane receptor. Drug metabolism and disposition: the biological fate of chemicals. 2009. Tolson Antonia H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Explaining variability in tacrolimus pharmacokinetics to optimize early exposure in adult kidney transplant recipients. Therapeutic drug monitoring. 2009. Press Rogier R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Structural basis of human pregnane X receptor activation by the hops constituent colupulone. Molecular pharmacology. 2008. Teotico Denise G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PXR pharmacogenetics: association of haplotypes with hepatic CYP3A4 and ABCB1 messenger RNA expression and doxorubicin clearance in Asian breast cancer patients. Clinical cancer research : an official journal of the American Association for Cancer Research. 2008. Sandanaraj Edwin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Identification of Ginkgo biloba as a novel activator of pregnane X receptor. Drug metabolism and disposition: the biological fate of chemicals. 2008. Yeung Eugene Y H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PXR: a xenobiotic receptor of diverse function implicated in pharmacogenetics. Pharmacogenomics. 2008. Zhang Bin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Influence of CYP3A5, ABCB1 and NR1I2 polymorphisms on prednisolone pharmacokinetics in renal transplant recipients. Steroids. 2008. Miura Masatomo, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine. Drug metabolism and disposition: the biological fate of chemicals. 2008. Yasuda Kazuto, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Machine learning methods and docking for predicting human pregnane X receptor activation. Chemical research in toxicology. 2008. Khandelwal Akash, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Role of human pregnane X receptor in tamoxifen- and 4-hydroxytamoxifen-mediated CYP3A4 induction in primary human hepatocytes and LS174T cells. Drug metabolism and disposition: the biological fate of chemicals. 2008. Sane Rucha S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Sterol regulatory element binding protein 1 interacts with pregnane X receptor and constitutive androstane receptor and represses their target genes. Pharmacogenetics and genomics. 2008. Roth Adrian, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Azole antimycotics differentially affect rifampicin-induced pregnane X receptor-mediated CYP3A4 gene expression. Drug metabolism and disposition: the biological fate of chemicals. 2008. Svecova Lucie, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of cyclosporine in children suggests an age-dependent influence of ABCB1 polymorphisms. Pharmacogenetics and genomics. 2008. Fanta Samuel, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Novel single nucleotide polymorphisms in the promoter and intron 1 of human pregnane X receptor/NR1I2 and their association with CYP3A4 expression. Drug metabolism and disposition: the biological fate of chemicals. 2008. Lamba Jatinder, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pyrethroids: cytotoxicity and induction of CYP isoforms in human hepatocytes. Drug metabolism and drug interactions. 2008. Das Parikshit C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Association of polymorphisms in NR1I2 and ABCB1 genes with epilepsy treatment responses. Pharmacogenomics. 2007. Hung Chin-Chuan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Valproic acid induces CYP3A4 and MDR1 gene expression by activation of constitutive androstane receptor and pregnane X receptor pathways. Drug metabolism and disposition: the biological fate of chemicals. 2007. Cerveny Lukas, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effect of HMGCoA reductase inhibitors on cytochrome P450 expression in endothelial cell line. Journal of cardiovascular pharmacology. 2007. Bertrand-Thiebault Céline, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007. Mensah-Osman Edith J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Relative activation of human pregnane X receptor versus constitutive androstane receptor defines distinct classes of CYP2B6 and CYP3A4 inducers. The Journal of pharmacology and experimental therapeutics. 2007. Faucette Stephanie R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Transcriptional profiling of genes induced in the livers of patients treated with carbamazepine. Clinical pharmacology and therapeutics. 2006. Oscarson Mikael, et al. PubMed
Human pregnane X receptor: genetic polymorphisms, alternative mRNA splice variants, and cytochrome P450 3A metabolic activity. Journal of clinical pharmacology. 2006. He Ping, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interactions between natural health products and antiretroviral drugs: pharmacokinetic and pharmacodynamic effects. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2006. Lee Lawrence S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Ketoconazole and miconazole are antagonists of the human glucocorticoid receptor: consequences on the expression and function of the constitutive androstane receptor and the pregnane X receptor. Molecular pharmacology. 2006. Duret Cedric, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Evaluation of 170 xenobiotics as transactivators of human pregnane X receptor (hPXR) and correlation to known CYP3A4 drug interactions. Current drug metabolism. 2006. Sinz Michael, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Polymorphism discovery in 51 chemotherapy pathway genes. Human molecular genetics. 2005. Freimuth Robert R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Overview of the pharmacogenetics of HIV therapy. The pharmacogenomics journal. 2006. Rodríguez-Nóvoa S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Molecular pharmacology. 2005. Burk Oliver, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Functional characterization of a novel polymorphism of pregnane X receptor, Q158K, in Chinese subjects. Pharmacogenetics and genomics. 2005. Lim Yun-Ping, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with rifampin and phenobarbital. Journal of clinical pharmacology. 2004. Hariparsad Niresh, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The induction of cytochrome P450 3A5 (CYP3A5) in the human liver and intestine is mediated by the xenobiotic sensors pregnane X receptor (PXR) and constitutively activated receptor (CAR). The Journal of biological chemistry. 2004. Burk Oliver, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Human PXR variants and their differential effects on the regulation of human UDP-glucuronosyltransferase gene expression. Drug metabolism and disposition: the biological fate of chemicals. 2004. Gardner-Stephen Dione, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Characterization of six base pair deletion in the putative HNF1-binding site of human PXR promoter. Journal of human genetics. 2003. Uno Yasuhiro, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Development of a real-time in vivo transcription assay: application reveals pregnane X receptor-mediated induction of CYP3A4 by cancer chemotherapeutic agents. Molecular pharmacology. 2002. Schuetz Erin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Molecular pharmacology. 2002. Maglich Jodi M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Putative role of the orphan nuclear receptor SXR (steroid and xenobiotic receptor) in the mechanism of CYP3A4 inhibition by xenobiotics. The Journal of biological chemistry. 2002. Takeshita Akira, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Bosentan, a dual endothelin receptor antagonist, activates the pregnane X nuclear receptor. European journal of pharmacology. 2002. van Giersbergen Paul L M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug metabolism and disposition: the biological fate of chemicals. 2002. Luo Gang, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Expression of CYP3A4, CYP2B6, and CYP2C9 is regulated by the vitamin D receptor pathway in primary human hepatocytes. The Journal of biological chemistry. 2002. Drocourt Lionel, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A cell-based reporter gene assay for determining induction of CYP3A4 in a high-volume system. The Journal of pharmacology and experimental therapeutics. 2002. Raucy Judy, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. The Journal of biological chemistry. 2002. Kast Heidi R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Transcriptional control of intestinal cytochrome P-4503A by 1alpha,25-dihydroxy vitamin D3. Molecular pharmacology. 2001. Thummel K E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Natural protein variants of pregnane X receptor with altered transactivation activity toward CYP3A4. Drug metabolism and disposition: the biological fate of chemicals. 2001. Hustert E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Calcium channel modulators of the dihydropyridine family are human pregnane X receptor activators and inducers of CYP3A, CYP2B, and CYP2C in human hepatocytes. Drug metabolism and disposition: the biological fate of chemicals. 2001. Drocourt L, et al. PubMed
The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics. 2001. Zhang J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR. The Journal of biological chemistry. 2001. Dussault I, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. The Journal of biological chemistry. 2001. Geick A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The effect of rifampin treatment on intestinal expression of human MRP transporters. The American journal of pathology. 2000. Fromm M F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Humanized xenobiotic response in mice expressing nuclear receptor SXR. Nature. 2000. Xie W, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proceedings of the National Academy of Sciences of the United States of America. 2000. Moore L B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effect of the adrenal 11-beta-hydroxylase inhibitor metyrapone on human hepatic cytochrome P-450 expression: induction of cytochrome P-450 3A4. Drug metabolism and disposition: the biological fate of chemicals. 2000. Harvey J L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. The Journal of biological chemistry. 2000. Moore L B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Molecular endocrinology (Baltimore, Md.). 2000. Jones S A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes & development. 1998. Blumberg B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proceedings of the National Academy of Sciences of the United States of America. 1998. Bertilsson G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. The Journal of clinical investigation. 1998. Lehmann J M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell. 1998. Kliewer S A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Omeprazole and lansoprazole are mixed inducers of CYP1A and CYP3A in human hepatocytes in primary culture. The Journal of pharmacology and experimental therapeutics. 1994. Curi-Pedrosa R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ftp://ftpguest:4guest@ftp.pharmgkb.org/download/PKB_N00000015.pdf. [URL:ftp://ftpguest:4guest@ftp.pharmgkb.org/download/PKB_N00000015.pdf]

LinkOuts

UniProtKB:
NR1I2_HUMAN (O75469)
Ensembl:
ENSG00000144852
GenAtlas:
NR1I2
GeneCard:
NR1I2
MutDB:
NR1I2
ALFRED:
LO037678F
HuGE:
NR1I2
Comparative Toxicogenomics Database:
8856
ModBase:
Q9UJ26
HumanCyc Gene:
HS07212
HGNC:
7968

Common Searches