NR1I2

Summary

NR1I2 (nuclear receptor subfamily 1 group I member 2, HGNC:7968) is a protein-coding gene on chromosome 3q13.33, encoding Nuclear receptor subfamily 1 group I member 2 (O75469). Nuclear receptor that acts as a transcription factor regulating genes involved in the metabolism and excretion of xenobiotics, drugs, and endogenous compounds.

This gene product belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain. The encoded protein is a transcriptional regulator of the cytochrome P450 gene CYP3A4, binding to the response element of the CYP3A4 promoter as a heterodimer with the 9-cis retinoic acid receptor RXR. It is activated by a range of compounds that induce CYP3A4, including dexamethasone and rifampicin. Several alternatively spliced transcripts encoding different isoforms, some of which use non-AUG (CUG) translation initiation codon, have been described for this gene. Additional transcript variants exist, however, they have not been fully characterized.

Source: NCBI Gene 8856 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pediatric lymphoma (Limited, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 86 total
• Druggable target: yes — 257 molecules with ChEMBL bioactivity
• Transcription factor: yes — 240 downstream targets (CollecTRI)
• MANE Select transcript: NM_003889

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7968
Approved symbol	NR1I2
Name	nuclear receptor subfamily 1 group I member 2
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	ONR1, PXR, BXR, SXR, PAR2
Ensembl gene	ENSG00000144852
Ensembl biotype	protein_coding
OMIM	603065
Entrez	8856

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000337940, ENST00000393716, ENST00000466380, ENST00000474090, ENST00000493757

RefSeq mRNA: 3 — MANE Select: NM_003889 NM_003889, NM_022002, NM_033013

CCDS: CCDS2995, CCDS43136, CCDS54627

Canonical transcript exons

ENST00000393716 — 9 exons

Exon	Start	End
ENSE00000967516	119810061	119810194
ENSE00000967517	119811539	119811726
ENSE00003525815	119815323	119815439
ENSE00003562670	119812686	119812960
ENSE00003587939	119807229	119807447
ENSE00003616667	119814979	119815121
ENSE00003679430	119815726	119815831
ENSE00003911743	119782101	119782300
ENSE00003912446	119817068	119818487

Expression profiles

Bgee: expression breadth ubiquitous, 107 present calls, max score 95.92.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2852 / max 97.7043, expressed in 26 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38157	0.1760	26
38156	0.0425	19
38155	0.0424	16
38154	0.0149	7
38153	0.0094	6

Top tissues by expression

256 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	95.92	gold quality
jejunal mucosa	UBERON:0000399	94.75	gold quality
mucosa of transverse colon	UBERON:0004991	93.55	gold quality
liver	UBERON:0002107	92.33	gold quality
duodenum	UBERON:0002114	91.90	gold quality
rectum	UBERON:0001052	90.54	gold quality
ileal mucosa	UBERON:0000331	88.22	gold quality
colonic mucosa	UBERON:0000317	87.80	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.46	gold quality
small intestine	UBERON:0002108	86.17	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.03	gold quality
gall bladder	UBERON:0002110	83.29	gold quality
transverse colon	UBERON:0001157	82.53	gold quality
parotid gland	UBERON:0001831	82.44	gold quality
jejunum	UBERON:0002115	81.69	gold quality
type B pancreatic cell	CL:0000169	75.96	gold quality
intestine	UBERON:0000160	75.35	gold quality
olfactory bulb	UBERON:0002264	75.22	gold quality
endometrium epithelium	UBERON:0004811	74.23	gold quality
large intestine	UBERON:0000059	71.67	gold quality
heart right ventricle	UBERON:0002080	71.26	gold quality
colon	UBERON:0001155	71.02	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	70.65	gold quality
nasal cavity epithelium	UBERON:0005384	69.52	gold quality
caecum	UBERON:0001153	68.47	gold quality
vermiform appendix	UBERON:0001154	68.27	gold quality
biceps brachii	UBERON:0001507	68.09	gold quality
colonic epithelium	UBERON:0000397	68.00	gold quality
diaphragm	UBERON:0001103	67.79	gold quality
endothelial cell	CL:0000115	67.22	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.52

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

240 targets.

Target	Regulation
A2ML1
ABCA1	Unknown
ABCB1	Activation
ABCC2
ABCC3	Activation
ABCG2	Activation
AC013461.1
ADAMTSL4
AKR1B15
ALG1
ALG1L1P
AP1G1
APP
ARAP1
ARAP3
ARFGEF2
ARID3C
ARNT2
ASS1
ATG4C
ATXN2
AURKB
B4GALT1
BBC3
BCL2	Activation
BCL2L1	Activation
BCL9L
BPHL
BPIFA4P
CA11

JASPAR motifs

Motif	Name	Family
MA1533.1	NR1I2	Thyroid hormone receptor-related factors (NR1)
MA1533.2	NR1I2	Thyroid hormone receptor-related factors (NR1)

JASPAR matrix evidence (PMIDs): PMID:12016543

Upstream regulators (CollecTRI, top): CDX2, CTNNB1, DR1, ETS1, HNF1A, HNF4A, LEF1, NCOA2, NCOR2, NFKB, NR0B2, NR1H3, NR1H4, NR1I2, NR1I3, NR3C1, PAX5, PPARA, PROX1, RELA, SPI1, TCF3

miRNA regulators (miRDB)

35 targeting NR1I2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4735-3P	99.14	69.85	777
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-3908	98.75	67.31	1160
HSA-MIR-640	98.44	66.93	644
HSA-MIR-532-5P	98.43	67.53	760
HSA-MIR-124-5P	98.11	67.65	1095
HSA-MIR-6772-3P	97.04	65.89	784
HSA-MIR-4727-3P	96.75	64.97	415
HSA-MIR-1292-5P	96.74	62.14	238

Literature-anchored findings (GeneRIF, showing 40)

• promiscuous nuclear receptor that responds to a wide variety of drugs, xenobiotics and endogenous compounds, and plays a critical role in mediating drug-drug interactions in humans (PMID:11865669)
• Role of SXR in xenobiotic inhibition of CYP3A4 promotor activity (PMID:12072427)
• mediates the proliferative action of mast-cell tryptase: possible relevance to human fibrotic disorders (PMID:12397176)
• alternative splicings for hPXR may largely contribute to the interindividual variability in CYP3A4 and P-glycoprotein induction (PMID:12413960)
• Pregnane X receptor mRNA expression levels are compared in a panel of 12 individual human liver samples; a 27-fold variability in PXR mRNA expression is found. (PMID:12485946)
• human PXR requires a specific agonist different from that required in mice to induce cyp3A expression (PMID:12569201)
• results provide evidence that the nuclear import of SXR is mediated by bipartite type of nuclear localization signal, which is recognized by three groups of importin adaptors for targeting the nuclear rim (PMID:12606758)
• control of steroid, heme, and carcinogen metabolism by this protein in transgenic mice (PMID:12644700)
• The present data indicate that SXR is a key system to induce, maintain and reverse a cisplatin-resistant phenotype in endometrial cancer cells. (PMID:12760308)
• 2.0A crystal structure of the human PXR ligand-binding domain (LBD) in complex with the cholesterol-lowering compound SR12813 and a 25 amino acid residue fragment of the human steroid receptor coactivator-1 (SRC-1) containing one LXXLL motif (PMID:12909012)
• steroid and xenobiotic receptor(SXR) has a novel role as a mediator of bone homeostasis in addition to its role as a xenobiotic sensor (PMID:12920130)
• individual variation in pregnane X receptor expression may account for differential expression of some UDP-glucuronosyltransferase isoforms between subjects (PMID:14977869)
• pregnane X receptor is a major determinant of CYP2B6-inducible expression (PMID:14977870)
• pregnane X receptor (PXR) and constitutively activated receptor (CAR) mediate induction of CYP3A5 in human liver and intestine (PMID:15252010)
• PXR-mediated gene regulation is affected by its DNA binding site (PMID:15316010)
• ligand-activated PXR interferes with HNF-4 signaling by targeting the common coactivator PGC-1, which underlies physiologically relevant inhibitory cross-talk between drug metabolism and cholesterol/glucose metabolism (PMID:15322103)
• expressed approximately 250-fold lower in peripheral blood mononuclear cells than in liver, and significantly correlated to MDR1 mRNA (PMID:15535420)
• xenobiotics and drugs can modulate 25-hydroxyvitamin D(3)-24-hydroxylase gene expression and alter vitamin D(3) hormonal activity and calcium homeostasis through the activation of PXR (PMID:15630458)
• findings demonstrated age-related differences in the body’s capacity to metabolize steroids and xenobiotic compounds and suggest an important role for SXR and its target genes, CYP3A4 and MDR1 in this process (PMID:15713537)
• pxr polymorphism is associated with decreased expression of MDR1 mRNA in intestinal villi (PMID:15772695)
• there is cross talk between distal CAR/PXR sites and HNF4alpha binding sites in the CYP2C9 promoter and that the HNF4alpha sites are required for maximal induction of the CYP2C9 promoter. (PMID:15919766)
• role in transcriptional regulation of CYP2C8 (PMID:15933212)
• May be involved in metabolic detoxification in drug-induced osteomalacia. (PMID:15985196)
• PXR expression is required for Bcl-2 and Bcl-xL up-regulation upon PXR activators treatment in human and rat hepatocytes. (PMID:16085054)
• PXR was observed to be a predominantly nuclear protein maintaining a dynamic equilibrium between the nuclear and cytoplasmic compartments of interphase cells. (PMID:16297466)
• The minimal essential region for promoter activity has been mapped to a 160 bp region upstream of the transcription initiation site, an area that also showed nuclear protein binding. (PMID:16328955)
• structural models of the pregnane X receptor (PXR)complexes PXR-LBD/SMRT-ID1 and PXR-LBD/SMRT-ID2 reveal key interactions that account for binding preferences. (PMID:16452398)
• genetic variation in the PXR encoding gene, which has been associated with altered activity of PXR, is strongly associated with susceptibility to inflammatory bowel disease, crohn disease and ulcerative colitis. (PMID:16472590)
• cross-regulation of CD36 by PXR and PPARgamma suggests that this fatty acid transporter may function as a common target of orphan nuclear receptors in their regulation of lipid homeostasis (PMID:16556603)
• SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells (PMID:16606623)
• NF-kappaB p65 directly interacted with the DNA-binding domain of RXRalpha and may prevent its binding to the consensus DNA sequences, thus inhibiting the transactivation by the PXR.RXRalpha complex. (PMID:16608838)
• Data show that activation of steroid and xenobiotic receptor does not induce cytochrome P450, family 24 (CYP24)-mediated expression, but inhibits vitamin D receptor-mediated CYP24 promoter activity. (PMID:16691293)
• The pregnane X receptor is transcriptionally functional in human hepatic stellate cells and activators inhibit transdifferentiation and proliferation. (PMID:16831602)
• These results suggest that the unique Trp-Zip-mediated PXR homodimer plays a role in the function of this nuclear xenobiotic receptor. (PMID:16834332)
• hPXR activation in vivo increased P-glycoprotein activity and tightened the blood-brain barrier to methadone, reducing the drug’s CNS efficacy. This is the first demonstration of the ability of PXR to alter the efficacy of a CNS-acting drug. (PMID:16837625)
• clinical consequences for individuals undergoing therapeutic exposure to the wide variety of drugs that are also SXR agonists (PMID:16841097)
• CYP2A6 is induced via PXR and PGC-1alpha through the DR4-like element at the distal response region. (PMID:16857725)
• Functional SXR gene variants appear to modify disease course in PSC. (PMID:16952547)
• PXR is a potential endocrine disrupting factor that may have broad implications in steroid homeostasis and drug-hormone interactions (PMID:16973756)
• Dietary isothiocyanate sulforaphane is the first identified naturally occurring antagonist for SXR. (PMID:17028159)

Cross-species orthologs

186 orthologs

Organism	Symbol	Gene ID
danio_rerio	nr1i2	ENSDARG00000029766
mus_musculus	Nr1i2	ENSMUSG00000022809
rattus_norvegicus	Nr1i2	ENSRNOG00000002906
drosophila_melanogaster	EcR	FBGN0000546
drosophila_melanogaster	Hr96	FBGN0015240
caenorhabditis_elegans		WBGENE00001062
caenorhabditis_elegans	nhr-2	WBGENE00003601
caenorhabditis_elegans		WBGENE00003608
caenorhabditis_elegans		WBGENE00003611
caenorhabditis_elegans		WBGENE00003614
caenorhabditis_elegans		WBGENE00003615
caenorhabditis_elegans		WBGENE00003617
caenorhabditis_elegans		WBGENE00003618
caenorhabditis_elegans		WBGENE00003620
caenorhabditis_elegans		WBGENE00003624
caenorhabditis_elegans		WBGENE00003632
caenorhabditis_elegans		WBGENE00003634
caenorhabditis_elegans		WBGENE00003638
caenorhabditis_elegans		WBGENE00003640
caenorhabditis_elegans		WBGENE00003641
caenorhabditis_elegans		WBGENE00003642
caenorhabditis_elegans		WBGENE00003643
caenorhabditis_elegans		WBGENE00003644
caenorhabditis_elegans		WBGENE00003645
caenorhabditis_elegans		WBGENE00003646
caenorhabditis_elegans		WBGENE00003648
caenorhabditis_elegans		WBGENE00003649
caenorhabditis_elegans		WBGENE00003651
caenorhabditis_elegans		WBGENE00003653
caenorhabditis_elegans		WBGENE00003655
caenorhabditis_elegans		WBGENE00003658
caenorhabditis_elegans		WBGENE00003660
caenorhabditis_elegans		WBGENE00003662
caenorhabditis_elegans	nhr-73	WBGENE00003663
caenorhabditis_elegans	nhr-77	WBGENE00003667
caenorhabditis_elegans		WBGENE00003669
caenorhabditis_elegans	nhr-81	WBGENE00003671
caenorhabditis_elegans	nhr-82	WBGENE00003672
caenorhabditis_elegans		WBGENE00003676
caenorhabditis_elegans		WBGENE00003677
caenorhabditis_elegans		WBGENE00003680
caenorhabditis_elegans		WBGENE00003682
caenorhabditis_elegans		WBGENE00003684
caenorhabditis_elegans		WBGENE00003685
caenorhabditis_elegans		WBGENE00003686
caenorhabditis_elegans		WBGENE00003688
caenorhabditis_elegans		WBGENE00003689
caenorhabditis_elegans		WBGENE00003692
caenorhabditis_elegans		WBGENE00003693
caenorhabditis_elegans		WBGENE00003694
caenorhabditis_elegans		WBGENE00003696
caenorhabditis_elegans		WBGENE00003698
caenorhabditis_elegans		WBGENE00003699
caenorhabditis_elegans		WBGENE00003700
caenorhabditis_elegans		WBGENE00003702
caenorhabditis_elegans		WBGENE00003704
caenorhabditis_elegans		WBGENE00003705
caenorhabditis_elegans		WBGENE00003707
caenorhabditis_elegans		WBGENE00003708
caenorhabditis_elegans		WBGENE00003712
caenorhabditis_elegans		WBGENE00003713
caenorhabditis_elegans		WBGENE00003714
caenorhabditis_elegans		WBGENE00003715
caenorhabditis_elegans		WBGENE00003716
caenorhabditis_elegans		WBGENE00003717
caenorhabditis_elegans		WBGENE00003718
caenorhabditis_elegans		WBGENE00003720
caenorhabditis_elegans		WBGENE00003721
caenorhabditis_elegans		WBGENE00003722
caenorhabditis_elegans		WBGENE00003723
caenorhabditis_elegans		WBGENE00003724
caenorhabditis_elegans		WBGENE00003725
caenorhabditis_elegans		WBGENE00003728
caenorhabditis_elegans		WBGENE00006471
caenorhabditis_elegans	unc-55	WBGENE00006790
caenorhabditis_elegans		WBGENE00007367
caenorhabditis_elegans		WBGENE00008056
caenorhabditis_elegans	nhr-165	WBGENE00008158
caenorhabditis_elegans		WBGENE00008208
caenorhabditis_elegans	nhr-169	WBGENE00008289
caenorhabditis_elegans		WBGENE00008309
caenorhabditis_elegans	nhr-174	WBGENE00008474
caenorhabditis_elegans		WBGENE00008619
caenorhabditis_elegans		WBGENE00008630
caenorhabditis_elegans		WBGENE00008778
caenorhabditis_elegans		WBGENE00008830
caenorhabditis_elegans		WBGENE00008884
caenorhabditis_elegans		WBGENE00008901
caenorhabditis_elegans	nhr-265	WBGENE00009608
caenorhabditis_elegans		WBGENE00010017
caenorhabditis_elegans		WBGENE00010180
caenorhabditis_elegans		WBGENE00010186
caenorhabditis_elegans		WBGENE00010215
caenorhabditis_elegans		WBGENE00010410
caenorhabditis_elegans		WBGENE00010600
caenorhabditis_elegans		WBGENE00010601
caenorhabditis_elegans		WBGENE00010602
caenorhabditis_elegans		WBGENE00010603
caenorhabditis_elegans		WBGENE00010604
caenorhabditis_elegans		WBGENE00011002
caenorhabditis_elegans		WBGENE00011150
caenorhabditis_elegans		WBGENE00011396
caenorhabditis_elegans		WBGENE00011520
caenorhabditis_elegans		WBGENE00011565
caenorhabditis_elegans		WBGENE00011566
caenorhabditis_elegans		WBGENE00011568
caenorhabditis_elegans	nhr-217	WBGENE00011651
caenorhabditis_elegans		WBGENE00011750
caenorhabditis_elegans		WBGENE00012050
caenorhabditis_elegans		WBGENE00012056
caenorhabditis_elegans		WBGENE00012446
caenorhabditis_elegans		WBGENE00012449
caenorhabditis_elegans		WBGENE00012596
caenorhabditis_elegans		WBGENE00012703
caenorhabditis_elegans		WBGENE00013067
caenorhabditis_elegans		WBGENE00013483
caenorhabditis_elegans	nhr-276	WBGENE00013512
caenorhabditis_elegans		WBGENE00013584
caenorhabditis_elegans		WBGENE00013940
caenorhabditis_elegans		WBGENE00014068
caenorhabditis_elegans	nhr-245	WBGENE00014189
caenorhabditis_elegans		WBGENE00014193
caenorhabditis_elegans		WBGENE00015497
caenorhabditis_elegans		WBGENE00015758
caenorhabditis_elegans		WBGENE00015897
caenorhabditis_elegans		WBGENE00015900
caenorhabditis_elegans		WBGENE00015901
caenorhabditis_elegans		WBGENE00015902
caenorhabditis_elegans		WBGENE00016091
caenorhabditis_elegans		WBGENE00016233
caenorhabditis_elegans		WBGENE00016364
caenorhabditis_elegans		WBGENE00016365
caenorhabditis_elegans		WBGENE00016366
caenorhabditis_elegans		WBGENE00016367
caenorhabditis_elegans		WBGENE00016368
caenorhabditis_elegans		WBGENE00016517
caenorhabditis_elegans		WBGENE00016772
caenorhabditis_elegans		WBGENE00016926
caenorhabditis_elegans		WBGENE00016927
caenorhabditis_elegans		WBGENE00017503
caenorhabditis_elegans		WBGENE00017512
caenorhabditis_elegans		WBGENE00017961
caenorhabditis_elegans		WBGENE00018189
caenorhabditis_elegans		WBGENE00018265
caenorhabditis_elegans		WBGENE00018266
caenorhabditis_elegans		WBGENE00018404
caenorhabditis_elegans		WBGENE00018412
caenorhabditis_elegans		WBGENE00018415
caenorhabditis_elegans		WBGENE00018539
caenorhabditis_elegans		WBGENE00018541
caenorhabditis_elegans		WBGENE00018542
caenorhabditis_elegans		WBGENE00018544
caenorhabditis_elegans		WBGENE00018545
caenorhabditis_elegans		WBGENE00018622
caenorhabditis_elegans		WBGENE00019115
caenorhabditis_elegans		WBGENE00019116
caenorhabditis_elegans		WBGENE00019741
caenorhabditis_elegans		WBGENE00019742
caenorhabditis_elegans		WBGENE00019743
caenorhabditis_elegans		WBGENE00020015
caenorhabditis_elegans		WBGENE00020062
caenorhabditis_elegans		WBGENE00020152
caenorhabditis_elegans		WBGENE00020153
caenorhabditis_elegans		WBGENE00020385
caenorhabditis_elegans		WBGENE00020460
caenorhabditis_elegans		WBGENE00020555
caenorhabditis_elegans		WBGENE00020750
caenorhabditis_elegans		WBGENE00020849
caenorhabditis_elegans		WBGENE00020850
caenorhabditis_elegans		WBGENE00020851
caenorhabditis_elegans		WBGENE00020852
caenorhabditis_elegans		WBGENE00021163
caenorhabditis_elegans		WBGENE00021522
caenorhabditis_elegans		WBGENE00021610
caenorhabditis_elegans		WBGENE00021611
caenorhabditis_elegans		WBGENE00021617
caenorhabditis_elegans		WBGENE00022097
caenorhabditis_elegans		WBGENE00022637
caenorhabditis_elegans		WBGENE00022639
caenorhabditis_elegans		WBGENE00022640
caenorhabditis_elegans		WBGENE00022726
caenorhabditis_elegans		WBGENE00022756
caenorhabditis_elegans		WBGENE00022805
caenorhabditis_elegans		WBGENE00044353
caenorhabditis_elegans		WBGENE00044699
caenorhabditis_elegans		WBGENE00045515

Paralogs (18): NR1H4 (ENSG00000012504), NR1H3 (ENSG00000025434), RORA (ENSG00000069667), RARB (ENSG00000077092), VDR (ENSG00000111424), PPARD (ENSG00000112033), THRA (ENSG00000126351), NR1D1 (ENSG00000126368), NR1H2 (ENSG00000131408), RARA (ENSG00000131759), PPARG (ENSG00000132170), NR1I3 (ENSG00000143257), RORC (ENSG00000143365), THRB (ENSG00000151090), RARG (ENSG00000172819), NR1D2 (ENSG00000174738), PPARA (ENSG00000186951), RORB (ENSG00000198963)

Protein

Protein identifiers

Nuclear receptor subfamily 1 group I member 2 — O75469 (reviewed: O75469)

Alternative names: Orphan nuclear receptor PAR1, Orphan nuclear receptor PXR, Pregnane X receptor, Steroid and xenobiotic receptor

All UniProt accessions (4): O75469, F1D8P9, H0Y8E2, J3KPQ3

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear receptor that acts as a transcription factor regulating genes involved in the metabolism and excretion of xenobiotics, drugs, and endogenous compounds. Activated by a broad range of endogenous steroids (e.g. pregnenolone, progesterone) and xenobiotics, including the antibiotic rifampicin and certain plant-derived metabolites. Upon ligand binding, translocates to the nucleus, forms a heterodimer with the retinoid X receptor/RXR, and binds to response elements in target promoters, leading to transcriptional activation. Target genes include cytochrome P450 enzymes such as CYP3A4 and ATP-binding cassette transporters including ABCB1/MDR1.

Subunit / interactions. Heterodimer with RXR. Interacts with NCOA1. Interacts (via domain NR LBD) with CRY1 and CRY2 in a ligand-dependent manner. Interacts with FBXO44; this interaction promotes NR1I2 ubiquitination and proteasomal degradation.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in liver, colon and small intestine.

Post-translational modifications. Phosphorylated by PKC at Thr-408. Ubiquitinated by RBCK1, leading to proteasomal degradation. Ubiquitinated in a FBXO44-dependent manner also leads to proteasomal degradation.

Similarity. Belongs to the nuclear hormone receptor family. NR1 subfamily.

Isoforms (7)

UniProt ID	Names	Canonical?
O75469-1	1A, 1, PRR1-A	yes
O75469-2	1B, PRR1-B
O75469-3	1C, PRR1-C
O75469-4	2A, 2, PRR2-A
O75469-5	2B, PRR2-B
O75469-6	2C, PRR2-C
O75469-7	3

RefSeq proteins (3): NP_003880, NP_071285, NP_148934 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001628	Znf_hrmn_rcpt	Domain
IPR001723	Nuclear_hrmn_rcpt	Family
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR035500	NHR-like_dom_sf	Homologous_superfamily
IPR050234	Nuclear_hormone_rcpt_NR1	Family

Pfam: PF00104, PF00105

UniProt features (53 total): helix 14, sequence variant 10, strand 7, splice variant 4, mutagenesis site 3, binding site 3, sequence conflict 2, zinc finger region 2, turn 2, chain 1, domain 1, modified residue 1, DNA-binding region 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

80 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9FZJ	X-RAY DIFFRACTION	1.6
6TFI	X-RAY DIFFRACTION	1.85
7AXE	X-RAY DIFFRACTION	1.9
8R00	X-RAY DIFFRACTION	1.95
1NRL	X-RAY DIFFRACTION	2
3CTB	X-RAY DIFFRACTION	2
4X1F	X-RAY DIFFRACTION	2
7AXK	X-RAY DIFFRACTION	2
8CF9	X-RAY DIFFRACTION	2
9FZG	X-RAY DIFFRACTION	2
7AXC	X-RAY DIFFRACTION	2.05
7RIU	X-RAY DIFFRACTION	2.05
9O41	X-RAY DIFFRACTION	2.05
3HVL	X-RAY DIFFRACTION	2.1
7YFK	X-RAY DIFFRACTION	2.1
8R82	X-RAY DIFFRACTION	2.1
8SVX	X-RAY DIFFRACTION	2.14
1M13	X-RAY DIFFRACTION	2.15
7AX8	X-RAY DIFFRACTION	2.15
7AXI	X-RAY DIFFRACTION	2.15
8CH8	X-RAY DIFFRACTION	2.15
8F5Y	X-RAY DIFFRACTION	2.15
7RIV	X-RAY DIFFRACTION	2.2
8SVN	X-RAY DIFFRACTION	2.2
8SZV	X-RAY DIFFRACTION	2.2
6HTY	X-RAY DIFFRACTION	2.22
4X1G	X-RAY DIFFRACTION	2.25
5A86	X-RAY DIFFRACTION	2.25
7AX9	X-RAY DIFFRACTION	2.25
8E3N	X-RAY DIFFRACTION	2.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75469-F1	86.20	0.70

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 247; 285–288; 407

Post-translational modifications (1): 408

Mutagenesis-validated functional residues (3):

Position	Phenotype
66–67	abolishes nuclear localization; when associated with 91-a-a-92.
91–92	abolishes nuclear localization; when associated with 66-a-a-67.
408	reduced transcriptional activity and protein stability.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-4090294	SUMOylation of intracellular receptors

MSigDB gene sets: 172 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_DIGESTION, MORF_MSH3, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, MORF_BRCA1, TGACCTY_ERR1_Q2, MORF_ESR1, MORF_RAD51L3, PUJANA_CHEK2_PCC_NETWORK, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, MORF_CTSB, MORF_PRKCA, GOBP_MAINTENANCE_OF_GASTROINTESTINAL_EPITHELIUM, CAIRO_HEPATOBLASTOMA_DN, GOBP_DIGESTIVE_SYSTEM_PROCESS

GO Biological Process (16): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), xenobiotic metabolic process (GO:0006805), signal transduction (GO:0007165), steroid metabolic process (GO:0008202), gene expression (GO:0010467), positive regulation of gene expression (GO:0010628), cell differentiation (GO:0030154), intracellular receptor signaling pathway (GO:0030522), xenobiotic catabolic process (GO:0042178), xenobiotic transport (GO:0042908), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), intestinal epithelial structure maintenance (GO:0060729), cellular response to molecule of bacterial origin (GO:0071219)

GO Molecular Function (13): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), nuclear receptor binding (GO:0016922), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), nuclear body (GO:0016604), intermediate filament cytoskeleton (GO:0045111)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Generic Transcription Pathway	1
SUMO E3 ligases SUMOylate target proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
DNA-templated transcription	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
regulation of gene expression	2
transcription cis-regulatory region binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
regulation of RNA biosynthetic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
lipid metabolic process	1
macromolecule biosynthetic process	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
cellular developmental process	1
intracellular signal transduction	1
xenobiotic metabolic process	1
catabolic process	1
transport	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
maintenance of gastrointestinal epithelium	1
response to molecule of bacterial origin	1
cellular response to biotic stimulus	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
intracellular receptor signaling pathway	1
signaling receptor activity	1

Protein interactions and networks

STRING

2286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NR1I2	RXRA	P19793	982
NR1I2	CYP3A4	P05184	956
NR1I2	NR0B2	Q15466	933
NR1I2	XPR1	Q9UBH6	889
NR1I2	NCOA1	Q15788	883
NR1I2	EPRS1	P07814	882
NR1I2	CYP3A7	P24462	865
NR1I2	CYP2B6	P20813	864
NR1I2	SLCO1B1	Q9Y6L6	840
NR1I2	UGT1A6	P19224	838
NR1I2	CYP7A1	P22680	835
NR1I2	CYP2C9	P11712	833
NR1I2	ABCB1	P08183	833
NR1I2	ABCB11	O95342	820
NR1I2	F10	P00742	820

IntAct

59 interactions, top by confidence:

A	B	Type	Score
NCOA1	NR1I2	psi-mi:“MI:0915”(physical association)	0.600
NR1I2	NCOA1	psi-mi:“MI:0407”(direct interaction)	0.600
NR1I2	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.520
HSP90AB1	NR1I2	psi-mi:“MI:0915”(physical association)	0.520
	NR1I2	psi-mi:“MI:0915”(physical association)	0.500
	NR1I2	psi-mi:“MI:0914”(association)	0.500
NR1I2	TCERG1	psi-mi:“MI:0915”(physical association)	0.400
NR1I2	Sirt1	psi-mi:“MI:0915”(physical association)	0.400
	NR1I2	psi-mi:“MI:0915”(physical association)	0.370
CCL24	NR1I2	psi-mi:“MI:0915”(physical association)	0.370
CCL3L1	NR1I2	psi-mi:“MI:0915”(physical association)	0.370
CSF2	NR1I2	psi-mi:“MI:0915”(physical association)	0.370
CXCL2	NR1I2	psi-mi:“MI:0915”(physical association)	0.370
CXCL3	NR1I2	psi-mi:“MI:0915”(physical association)	0.370
IFNA10	NR1I2	psi-mi:“MI:0915”(physical association)	0.370
IFNA5	NR1I2	psi-mi:“MI:0915”(physical association)	0.370
IL12B	NR1I2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (100): NR1I2 (Two-hybrid), NR1I2 (Biochemical Activity), NR1I2 (Biochemical Activity), PSMC5 (Two-hybrid), NCOA1 (Two-hybrid), NR1I2 (Reconstituted Complex), NR1I2 (Two-hybrid), NR1I2 (Affinity Capture-Western), RXRB (Affinity Capture-MS), TP53 (Affinity Capture-MS), TP53 (Affinity Capture-Western), NR1I2 (Affinity Capture-Western), CEBPA (Affinity Capture-Western), NCOA1 (Two-hybrid), NR1I2 (Two-hybrid)

ESM2 similar proteins: A2T7D9, A3RGC1, O35627, O42295, O42450, O54915, O57606, O75469, P04625, P11473, P15204, P18113, P18115, P18117, P18119, P37242, P48281, P55055, P62044, P62045, P68305, P68306, Q02777, Q02965, Q13133, Q14994, Q1L673, Q28037, Q28570, Q28571, Q5E9B6, Q60644, Q62685, Q62755, Q8MIM3, Q8SQ01, Q90382, Q91241, Q91279, Q91424

Diamond homologs: A2T7D9, A2T928, A3RGC1, G5EFF5, O00482, O13124, O18531, O35627, O42101, O42295, O42392, O42450, O54915, O57606, O75469, O97716, P03373, P04625, P10276, P10827, P10828, P11416, P11473, P13053, P13631, P15204, P18113, P18115, P18117, P18119, P18514, P18911, P22448, P33242, P33244, P37242, P41235, P48281, P49700, P49701

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
NR0B2	down-regulates	NR1I2	binding
NR1I2	up-regulates	RXRA	binding
NR1I2	“up-regulates quantity by expression”	UGT1A1	“transcriptional regulation”
NR1I2	“up-regulates quantity by expression”	ABCB1	“transcriptional regulation”
NR1I2	“up-regulates quantity by expression”	CYP3A4	“transcriptional regulation”
clotrimazole	“up-regulates activity”	NR1I2	“chemical activation”
nifedipine	“up-regulates activity”	NR1I2	“chemical activation”
CDK2	“down-regulates quantity by destabilization”	NR1I2	phosphorylation
lovastatin	“up-regulates activity”	NR1I2	“chemical activation”
mifepristone	“up-regulates activity”	NR1I2	“chemical activation”
phenobarbital	“up-regulates activity”	NR1I2	“chemical activation”
“bis(2-ethylhexyl) phthalate”	“up-regulates activity”	NR1I2	“chemical activation”
“diisononyl phthalate”	“up-regulates activity”	NR1I2	“chemical activation”
“mono(2-ethylhexyl) phthalate”	“up-regulates activity”	NR1I2	“chemical activation”
“monoisononyl phthalate”	“up-regulates activity”	NR1I2	“chemical activation”
CDK5	“down-regulates activity”	NR1I2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
immune response	6	12.8×	7e-04
inflammatory response	6	10.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

86 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	5
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1501 predictions. Top by Δscore:

Variant	Effect	Δscore
3:119807350:G:GT	donor_gain	1.0000
3:119810191:GAGA:G	donor_gain	1.0000
3:119810193:GA:G	donor_gain	1.0000
3:119810195:G:GG	donor_gain	1.0000
3:119811533:CTGCA:C	acceptor_loss	1.0000
3:119811534:TGCA:T	acceptor_loss	1.0000
3:119811535:GCA:G	acceptor_loss	1.0000
3:119811536:CA:C	acceptor_loss	1.0000
3:119811537:A:AG	acceptor_gain	1.0000
3:119811537:AG:A	acceptor_loss	1.0000
3:119811537:AGT:A	acceptor_gain	1.0000
3:119811538:G:GA	acceptor_gain	1.0000
3:119811538:GTG:G	acceptor_gain	1.0000
3:119811663:G:GT	donor_gain	1.0000
3:119811682:A:G	donor_gain	1.0000
3:119812956:TTCAG:T	donor_loss	1.0000
3:119812957:TCAG:T	donor_loss	1.0000
3:119812958:CAG:C	donor_loss	1.0000
3:119812959:AGGTA:A	donor_loss	1.0000
3:119812960:GG:G	donor_loss	1.0000
3:119812961:G:A	donor_loss	1.0000
3:119812962:T:A	donor_loss	1.0000
3:119815155:G:T	donor_gain	1.0000
3:119815312:A:AG	acceptor_gain	1.0000
3:119815313:C:G	acceptor_gain	1.0000
3:119815315:A:AG	acceptor_gain	1.0000
3:119815316:T:G	acceptor_gain	1.0000
3:119815321:A:AG	acceptor_gain	1.0000
3:119815321:AG:A	acceptor_gain	1.0000
3:119815321:AGGT:A	acceptor_gain	1.0000

AlphaMissense

2881 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:119807407:T:C	F53L	0.999
3:119807409:C:A	F53L	0.999
3:119807409:C:G	F53L	0.999
3:119807436:G:C	K62N	0.999
3:119807436:G:T	K62N	0.999
3:119807440:T:C	F64L	0.999
3:119807442:T:A	F64L	0.999
3:119807442:T:G	F64L	0.999
3:119810183:T:C	M107T	0.999
3:119807380:T:A	C44S	0.998
3:119807381:G:C	C44S	0.998
3:119807407:T:A	F53I	0.998
3:119807423:G:A	C58Y	0.998
3:119807447:G:C	R66T	0.998
3:119810061:G:C	R66S	0.998
3:119810061:G:T	R66S	0.998
3:119810143:T:C	C94R	0.998
3:119807381:G:A	C44Y	0.997
3:119807408:T:C	F53S	0.997
3:119807422:T:C	C58R	0.997
3:119807431:T:A	C61S	0.997
3:119807432:G:C	C61S	0.997
3:119807443:T:C	F65L	0.997
3:119807445:C:A	F65L	0.997
3:119807445:C:G	F65L	0.997
3:119807447:G:T	R66M	0.997
3:119810143:T:A	C94S	0.997
3:119810144:G:C	C94S	0.997
3:119810155:C:A	R98S	0.997
3:119807380:T:C	C44R	0.996

dbSNP variants (sampled 300 via entrez): RS1000029807 (3:119816108 A>G), RS1000165620 (3:119804530 C>T), RS1000320491 (3:119782082 C>G,T), RS1000344634 (3:119798726 C>A), RS1000378364 (3:119805233 A>C), RS1000461187 (3:119792641 A>T), RS1000743148 (3:119792918 G>A), RS1000775273 (3:119801316 C>A), RS1000862909 (3:119780845 T>A,C,G), RS1000916793 (3:119780527 A>G), RS1000974842 (3:119787395 G>A), RS1001001768 (3:119815221 G>A), RS1001092862 (3:119787099 C>A), RS1001195315 (3:119816873 G>A,C,T), RS1001346236 (3:119803871 C>T)

Disease associations

OMIM: gene MIM:603065 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
pediatric lymphoma	Limited	Autosomal recessive

Mondo (1): pediatric lymphoma (MONDO:0003659)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST006614_63	Total cholesterol levels	2.000000e-10
GCST006993_4	Hippocampal volume in Alzheimer’s disease dementia	1.000000e-07
GCST010241_148	Apolipoprotein A1 levels	2.000000e-20
GCST010242_47	HDL cholesterol levels	9.000000e-15
GCST010245_121	LDL cholesterol levels	5.000000e-12
GCST90002389_25	Lymphocyte percentage of white cells	1.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0005035	hippocampal volume
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0007993	lymphocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3401 (SINGLE PROTEIN), CHEMBL6193812 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195531 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

257 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 707,673 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1075	MORICIZINE	4	3,860
CHEMBL1082407	ENZALUTAMIDE	4	9,652
CHEMBL1083659	SUVOREXANT	4	852
CHEMBL1111	AMBRISENTAN	4	7,009
CHEMBL112	ACETAMINOPHEN	4	157,242
CHEMBL1131	ACITRETIN	4	13,259
CHEMBL1146	CEFAMANDOLE	4	21,886
CHEMBL1159650	CLOBETASOL PROPIONATE	4	30,865
CHEMBL1163	ATAZANAVIR	4	22,094
CHEMBL1170	TESTOSTERONE PROPIONATE	4	17,619
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1198857	VILANTEROL	4	2,552
CHEMBL1200384	BETAMETHASONE DIPROPIONATE	4	12,700
CHEMBL1200402	AMLODIPINE BESYLATE	4	19,367
CHEMBL1200438	TIOCONAZOLE	4	15,162
CHEMBL1200592	DESOXYCORTICOSTERONE PIVALATE	4
CHEMBL1200596	CHLOROXINE	4
CHEMBL1200600	FLUOROMETHOLONE	4
CHEMBL1200617	RIMEXOLONE	4
CHEMBL1200666	CALCIPOTRIENE	4
CHEMBL1200807	NORELGESTROMIN	4
CHEMBL1200848	HYDROXYPROGESTERONE CAPROATE	4
CHEMBL1200865	LOTEPREDNOL ETABONATE	4
CHEMBL1200883	THONZONIUM BROMIDE	4
CHEMBL1200934	NORGESTIMATE	4

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

23 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10934498	Metabolism/PK	3	irinotecan	Colonic Neoplasms
rs1523130	Other	3	memantine	Dementia
rs1523130	Metabolism/PK	3	risperidone	Bipolar Disorder;Depression;Substance-Related Disorders
rs2276706	Other	3	repaglinide
rs2276707	Metabolism/PK	3	risperidone	Bipolar Disorder;Depression;Substance-Related Disorders
rs2276707	Metabolism/PK	3	tacrolimus	Kidney Transplantation
rs2461817	Metabolism/PK	3	carbamazepine	Epilepsy
rs2472677	Other	3	rifampin
rs2472677	Metabolism/PK	3	atazanavir	Acquired Immunodeficiency Syndrome;HIV infectious disease;Nephrolithiasis
rs2472677	Toxicity	3	dolutegravir	adverse events;Discontinuation
rs3732359	Toxicity	3	docetaxel	Anemia;Nasopharyngeal Neoplasms
rs3732360	Toxicity	3	docetaxel	Anemia;Nasopharyngeal Neoplasms
rs3814055	Metabolism/PK	3	carbamazepine	Epilepsy
rs3814055	Toxicity	3	flucloxacillin	Toxic liver disease
rs3814055	Toxicity,Metabolism/PK	3	sirolimus;temsirolimus	adverse events;Gastrointestinal toxicity;Myelosuppression;Urinary Bladder Neoplasms
rs3814055	Metabolism/PK	3	tacrolimus
rs3814058	Other	3	repaglinide
rs3814058	Toxicity	3	docetaxel	Anemia;Nasopharyngeal Neoplasms
rs4688040	Metabolism/PK	3	carbamazepine	Epilepsy
rs6785049	Toxicity	3	sunitinib	Neoplasms
rs6785049	Toxicity,Metabolism/PK	3	sirolimus;temsirolimus	Gastrointestinal toxicity;Myelosuppression;Urinary Bladder Neoplasms
rs7643645	Metabolism/PK	3	risperidone	Psychotic Disorder
rs7643645	Metabolism/PK	3	carbamazepine	Epilepsy

PharmGKB variants

30 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1054190	NR1I2		0.00	0
rs1054191	NR1I2		0.00	0
rs1464602	NR1I2		0.00	0
rs1464603	NR1I2		0.00	0
rs1523127	NR1I2		0.00	0
rs1523130	NR1I2	3	2.00	2	risperidone;memantine
rs2276706	NR1I2	3	1.50	1	repaglinide
rs2276707	NR1I2	3	1.50	2	risperidone;tacrolimus
rs2461817	NR1I2	3	1.75	1	carbamazepine
rs2472677	NR1I2	3	7.00	3	rifampin;atazanavir;dolutegravir
rs3732356	NR1I2		0.00	0
rs3732359	NR1I2	3	2.00	1	docetaxel
rs3732360	NR1I2	3	2.00	1	docetaxel
rs3814055	NR1I2	3	5.25	4	flucloxacillin;sirolimus;temsirolimus;carbamazepine;tacrolimus
rs3814057	NR1I2		0.00	0
rs3814058	NR1I2	3	2.50	2	repaglinide;docetaxel
rs3842689	NR1I2		0.00	0
rs4688040	NR1I2	3	1.25	1	carbamazepine
rs6785049	NR1I2	3	3.00	2	sunitinib;sirolimus;temsirolimus
rs7643645	NR1I2	3	3.88	2	risperidone;carbamazepine
rs12721613	NR1I2		0.00	0
rs12721616	NR1I2		0.00	0
rs13059232	NR1I2		0.00	0
rs72551372	NR1I2		0.00	0
rs72551374	NR1I2		0.00	0
rs10934498	NR1I2	3	2.50	1	irinotecan
rs2472682	NR1I2		0.00	0
rs16830505	NR1I2		0.00	0
rs2461823	NR1I2		0.00	0
rs3732357	NR1I2		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: nhr — 1I. Vitamin D receptor-like receptors

Most potent curated ligand interactions (17 total), top 17:

Ligand	Action	Affinity	Parameter
trabectedin	Antagonist	8.52	pIC50
hyperforin	Agonist	7.6	pEC50
SR12813	Agonist	6.7	pEC50
pregnenolone-16α-carbonitrile	Agonist	6.5	pEC50
garcinoic acid	Agonist	6.48	pKd
5β-pregnane-3,20-dione	Agonist	6.4	pIC50
(+)-S20	Agonist	6.4	pEC50
dexamethasone	Agonist	6.1	pEC50
lovastatin	Full agonist	6.0	pEC50
rifampicin	Agonist	6.0	pEC50
schisandrin A	Agonist	5.7	pEC50
S20	Agonist	5.7	pEC50
paclitaxel	Agonist	5.3	pEC50
5β-cholestane-3α,7α,12α-triol	Agonist	5.3	pEC50
lithocholic acid	Agonist	5.05	pEC50
mifepristone	Agonist	5.0	pEC50
3-keto-lithocholic acid	Agonist	4.8	pEC50

Binding affinities (BindingDB)

18 measured of 22 human assays (22 total across all organisms); most potent 18 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
N-[4-(1-cyclohexyl-2,2,2-trifluoro-1-hydroxyethyl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	EC50	3 nM
N-[4-(1,1,1,3,3,4,4,5,5,5-decafluoro-2-hydroxypentan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	EC50	10 nM
N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	IC50	13 nM
N-[4-(2,2,2-trifluoro-1-hydroxy-1-phenylethyl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	EC50	16 nM
N-[4-(1,1,1-trifluoro-2-hydroxybutan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	EC50	126 nM
N-[4-(1,1,1-trifluoro-2-hydroxypentan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	EC50	158 nM
N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	EC50	501 nM
N-[4-(1,1,1-trifluoro-2-hydroxy-4-phenylbut-3-yn-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	IC50	631 nM
N-[4-(2,2,2-trifluoro-1-hydroxyethyl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	EC50	1000 nM
CHEMBL3126839	EC50	1000 nM
N-(4-acetylphenyl)-N-(2,2,2-trifluoroethyl)benzenesulfonamide	IC50	1580 nM
N-[4-(1-hydroxyethyl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	IC50	2510 nM
CHEMBL4094467	EC50	2780 nM
MDL-72422	EC50	3500 nM
N-[4-(hydroxymethyl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	IC50	7940 nM
CHEMBL4081189	EC50	8330 nM
CHEMBL4067852	EC50	16700 nM
CHEMBL4061940	EC50	16700 nM

ChEMBL bioactivities

1096 potent at pChembl≥5 of 1421 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.15	EC50	0.7	nM	CHEMBL463678
9.00	IC50	1	nM	CHEMBL5284539
8.82	EC50	1.5	nM	CHEMBL464497
8.80	IC50	1.6	nM	CHEMBL5286515
8.70	EC50	2	nM	LINOLENIC ACID
8.62	IC50	2.4	nM	GUGGULSTERONE
8.62	IC50	2.4	nM	E-GUGGULSTERONE
8.50	EC50	3.162	nM	CHEMBL396952
8.40	EC50	4	nM	DROXIDOPA
8.40	IC50	4	nM	CHEMBL5277255
8.30	EC50	5	nM	CHEMBL4785075
8.22	IC50	6	nM	CHEMBL5284539
8.16	IC50	6.9	nM	CHEMBL5290088
8.16	IC50	6.9	nM	CHEMBL5281952
8.15	IC50	7	nM	CHEMBL5282848
8.15	IC50	7	nM	CHEMBL5285451
8.10	EC50	8	nM	T091317
8.10	EC50	8.04	nM	CHEMBL463678
8.10	EC50	8	nM	CHEMBL3781118
8.09	EC50	8.05	nM	CHEMBL464497
8.09	EC50	8.1	nM	CHEMBL5274748
8.05	IC50	9	nM	CHEMBL5277255
8.00	EC50	10	nM	CHEMBL4591380
8.00	EC50	10	nM	CHEMBL430006
7.96	IC50	11	nM	CHEMBL5274748
7.92	IC50	12	nM	CHEMBL5288280
7.90	EC50	12.59	nM	T091317
7.89	EC50	13	nM	CHEMBL465733
7.89	IC50	13	nM	CHEMBL5282848
7.85	IC50	14	nM	CHEMBL5274800
7.85	IC50	14	nM	CHEMBL5286999
7.85	IC50	14	nM	CHEMBL5284102
7.85	IC50	14	nM	CHEMBL5286515
7.85	IC50	14	nM	CHEMBL5284539
7.82	EC50	15	nM	T091317
7.82	IC50	15	nM	CHEMBL5277006
7.82	IC50	15	nM	CHEMBL5289969
7.80	EC50	16	nM	CHEMBL4209665
7.80	EC50	15.85	nM	CHEMBL242293
7.80	IC50	16	nM	CHEMBL5269977
7.80	IC50	16	nM	CHEMBL5290100
7.75	EC50	18	nM	CHEMBL4217418
7.75	IC50	18	nM	CHEMBL5281952
7.75	IC50	18	nM	CHEMBL5285451
7.70	EC50	20	nM	CHEMBL4210791
7.70	IC50	19.95	nM	CHEMBL430006
7.70	EC50	20	nM	CHEMBL457270
7.70	EC50	20	nM	CHEMBL464867
7.70	IC50	20	nM	CHEMBL5289969
7.66	IC50	22	nM	CHEMBL5276468

PubChem BioAssay actives

825 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(1-benzylbenzimidazol-5-yl)-2,3,4,5,6-pentamethylbenzenesulfonamide	381941: Agonist activity at human pregnane X receptor expressed in HGPXR reporter cells	ec50	0.0007	uM
N-[5-tert-butyl-2-[(2S)-pentan-2-yl]oxyphenyl]-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1936350: Inverse agonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition of receptor basal activity incubated for 24 hrs by luminescence based analysis	ic50	0.0010	uM
N-(1-benzylbenzimidazol-5-yl)-2,4,6-trimethylbenzenesulfonamide	381941: Agonist activity at human pregnane X receptor expressed in HGPXR reporter cells	ec50	0.0015	uM
N-(5-tert-butyl-2-pentan-2-yloxyphenyl)-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1936350: Inverse agonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition of receptor basal activity incubated for 24 hrs by luminescence based analysis	ic50	0.0016	uM
(9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid	1215087: Activation of human PXR expressed in human HepG2 (DPX-2) cells assessed as induction of CYP3A4 after 24 hrs by luminescent analysis	ec50	0.0020	uM
N-[4-(1-cyclohexyl-2,2,2-trifluoro-1-hydroxyethyl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	293511: Antagonist activity at human PXR by transient transfection assay	ec50	0.0032	uM
N-[5-tert-butyl-2-[(2S)-pentan-2-yl]oxyphenyl]-1-(2-methoxy-5-methylphenyl)-5-methyltriazole-4-carboxamide	1936346: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay	ic50	0.0040	uM
(3S,4S)-N-[(4-ethylsulfonylphenyl)methyl]-3-(4-fluorophenyl)-4-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-3-methylpyrrolidine-1-carboxamide	1721669: Activation of PXR (unknown origin)	ec50	0.0050	uM
N-(5-tert-butyl-2-pentan-2-yloxyphenyl)-1-(2-methoxy-5-methylphenyl)-5-methyltriazole-4-carboxamide	1936352: Antagonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition in rifampicin-induced receptor activation incubated for 24 hrs by luminescence based analysis	ic50	0.0069	uM
1-(5-bromo-2-methoxyphenyl)-N-(2-butoxy-5-tert-butylphenyl)-5-methyltriazole-4-carboxamide	1936350: Inverse agonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition of receptor basal activity incubated for 24 hrs by luminescence based analysis	ic50	0.0069	uM
N-[5-tert-butyl-2-(2-methylbutoxy)phenyl]-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1936346: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay	ic50	0.0070	uM
N-[5-tert-butyl-2-[(2S)-pentan-2-yl]oxyphenyl]-1-(5-chloro-2-methoxyphenyl)-5-methyltriazole-4-carboxamide	1936346: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay	ic50	0.0070	uM
N-[4-(2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	1943410: Activation of human PXR	ec50	0.0080	uM
N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	1368956: Transactivation of PXR in human HepG2 cells by receptor transactivation assay	ec50	0.0080	uM
N-[5-tert-butyl-2-[(2R)-pentan-2-yl]oxyphenyl]-1-(2-methoxy-5-methylphenyl)-5-methyltriazole-4-carboxamide	1936348: Agonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as transcriptional activation incubated for 24 hrs by luminescence based analysis	ec50	0.0081	uM
1,1,1,3,3,3-hexafluoro-2-[4-[1-(4-fluorophenyl)sulfonylcyclopentyl]phenyl]propan-2-ol	1542613: Transactivation of PXR in human HepG2 cells	ec50	0.0100	uM
N-[4-(1,1,1,3,3,4,4,5,5,5-decafluoro-2-hydroxypentan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	293511: Antagonist activity at human PXR by transient transfection assay	ec50	0.0100	uM
N-[5-tert-butyl-2-(3-methylbutoxy)phenyl]-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1936346: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay	ic50	0.0120	uM
N-(1-hexylbenzimidazol-5-yl)-2,3,4,5,6-pentamethylbenzenesulfonamide	381941: Agonist activity at human pregnane X receptor expressed in HGPXR reporter cells	ec50	0.0130	uM
N-(2-butoxy-5-tert-butylphenyl)-1-(2-methoxy-5-methylphenyl)-5-methyltriazole-4-carboxamide	1936346: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay	ic50	0.0140	uM
N-(3-tert-butyl-5-phenylphenyl)-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1936350: Inverse agonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition of receptor basal activity incubated for 24 hrs by luminescence based analysis	ic50	0.0140	uM
N-[5-tert-butyl-2-[(2R)-pentan-2-yl]oxyphenyl]-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1936350: Inverse agonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition of receptor basal activity incubated for 24 hrs by luminescence based analysis	ic50	0.0140	uM
N-(5-tert-butyl-2-pentan-2-yloxyphenyl)-1-(5-chloro-2-methoxyphenyl)-5-methyltriazole-4-carboxamide	1936352: Antagonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition in rifampicin-induced receptor activation incubated for 24 hrs by luminescence based analysis	ic50	0.0150	uM
N-[5-tert-butyl-2-[(2R)-pentan-2-yl]oxyphenyl]-1-(5-chloro-2-methoxyphenyl)-5-methyltriazole-4-carboxamide	1936346: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay	ic50	0.0150	uM
N-(2,2,2-trifluoroethyl)-N-[4-(2,2,2-trifluoro-1-hydroxy-1-phenylethyl)phenyl]benzenesulfonamide	293511: Antagonist activity at human PXR by transient transfection assay	ec50	0.0158	uM
1,1,1,3,3,3-hexafluoro-2-[1-(4-fluorophenyl)sulfonyl-4-methyl-3,4-dihydro-2H-quinolin-6-yl]propan-2-ol	1368956: Transactivation of PXR in human HepG2 cells by receptor transactivation assay	ec50	0.0160	uM
N-(2-butoxy-5-tert-butylphenyl)-1-(5-chloro-2-methoxyphenyl)-5-methyltriazole-4-carboxamide	1936346: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay	ic50	0.0160	uM
N-(2-butoxy-5-tert-butylphenyl)-1-(2-chloro-5-methoxyphenyl)-5-methyltriazole-4-carboxamide	1936346: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay	ic50	0.0160	uM
1,1,1,3,3,3-hexafluoro-2-[1-(4-fluorophenyl)sulfonyl-4-methyl-2,3-dihydroquinoxalin-6-yl]propan-2-ol	1368956: Transactivation of PXR in human HepG2 cells by receptor transactivation assay	ec50	0.0180	uM
1,1,1,3,3,3-hexafluoro-2-[4-(4-fluorophenyl)sulfonyl-2,3-dihydro-1,4-benzothiazin-7-yl]propan-2-ol	1368956: Transactivation of PXR in human HepG2 cells by receptor transactivation assay	ec50	0.0200	uM
N-(1-benzylbenzimidazol-5-yl)naphthalene-1-sulfonamide	381941: Agonist activity at human pregnane X receptor expressed in HGPXR reporter cells	ec50	0.0200	uM
N-(1-benzylbenzimidazol-5-yl)-2-bromobenzenesulfonamide	381941: Agonist activity at human pregnane X receptor expressed in HGPXR reporter cells	ec50	0.0200	uM
N-(2-butoxy-5-tert-butylphenyl)-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1936346: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay	ic50	0.0220	uM
N-(2-butoxy-5-tert-butylphenyl)-1-(5-fluoro-2-methoxyphenyl)-5-methyltriazole-4-carboxamide	1936346: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay	ic50	0.0220	uM
N-(4-tert-butylphenyl)-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-sulfonamide	1936350: Inverse agonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition of receptor basal activity incubated for 24 hrs by luminescence based analysis	ic50	0.0220	uM
N-(1-benzylbenzimidazol-5-yl)-2-chlorobenzenesulfonamide	381941: Agonist activity at human pregnane X receptor expressed in HGPXR reporter cells	ec50	0.0230	uM
4-(4-tert-butylphenyl)sulfonyl-1-(2,5-dimethoxyphenyl)-5-methyltriazole	1775050: Inverse agonist activity at human PXR expressed in HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter incubated for 24 hrs by luciferase reporter assay	ic50	0.0240	uM
1,1,1,3,3,3-hexafluoro-2-[1-(4-fluorophenyl)sulfonyl-3,4-dihydro-2H-quinolin-6-yl]propan-2-ol	1368956: Transactivation of PXR in human HepG2 cells by receptor transactivation assay	ec50	0.0250	uM
N-(5-tert-butyl-2-propoxyphenyl)-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1936346: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay	ic50	0.0270	uM
N-(5-tert-butyl-2-hexoxyphenyl)-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1936346: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay	ic50	0.0270	uM
(1R,5R,7S,8R)-4-hydroxy-8-methyl-3,5,7-tris(3-methylbut-2-enyl)-8-(4-methylpent-3-enyl)-1-(2-methylpropanoyl)bicyclo[3.3.1]non-3-ene-2,9-dione	338905: Displacement of [3H]SR12813 from human PXR by scintillation proximity competition binding assay	ki	0.0270	uM
N-(2-butoxy-5-tert-butylphenyl)-1-(2-methoxyphenyl)-5-methyltriazole-4-carboxamide	1936346: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay	ic50	0.0280	uM
N-(1-benzylbenzimidazol-5-yl)-3,5-dimethylbenzenesulfonamide	381941: Agonist activity at human pregnane X receptor expressed in HGPXR reporter cells	ec50	0.0330	uM
1,1,1,3,3,3-hexafluoro-2-[1-(4-fluorophenyl)sulfonyl-4,4-dimethyl-2,3-dihydroquinolin-6-yl]propan-2-ol	1368956: Transactivation of PXR in human HepG2 cells by receptor transactivation assay	ec50	0.0360	uM
N-(5-tert-butyl-2-pentoxyphenyl)-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1936346: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay	ic50	0.0390	uM
N-[3-tert-butyl-5-(butylamino)phenyl]-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1936350: Inverse agonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition of receptor basal activity incubated for 24 hrs by luminescence based analysis	ic50	0.0390	uM
N-ethyl-N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide	1059091: Agonist activity at GAL4-fused human PXR expressed in HEK293T cells assessed as activation of basal transcriptional activity after 20 hrs by dual-glo luciferase reporter gene assay	ec50	0.0390	uM
N-(1-benzylbenzimidazol-5-yl)-4-tert-butylbenzenesulfonamide	381941: Agonist activity at human pregnane X receptor expressed in HGPXR reporter cells	ec50	0.0420	uM
N-(1-benzylbenzimidazol-5-yl)-2-methylbenzenesulfonamide	381941: Agonist activity at human pregnane X receptor expressed in HGPXR reporter cells	ec50	0.0450	uM
1,1,1-trifluoro-2-[4-[1-(4-fluorophenyl)sulfonylcyclopentyl]phenyl]butan-2-ol	1542613: Transactivation of PXR in human HepG2 cells	ec50	0.0480	uM

CTD chemical–gene interactions

683 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Rifampin	decreases expression, affects localization, increases activity, increases reaction, decreases reaction (+13 more)	118
bisphenol A	affects binding, decreases activity, increases activity, increases reaction, decreases reaction (+3 more)	21
SR 12813	increases activity, decreases response to substance, decreases reaction, increases expression, increases reaction (+2 more)	19
Ketoconazole	affects binding, affects cotreatment, decreases reaction, increases expression, decreases metabolic processing (+6 more)	14
Clotrimazole	increases activity, increases reaction, increases expression, affects reaction, affects binding	13
Diethylhexyl Phthalate	affects binding, increases activity, increases expression, increases reaction, decreases expression	12
Phenobarbital	increases reaction, increases activity, affects cotreatment, affects expression, affects binding (+2 more)	11
Dexamethasone	increases reaction, affects reaction, increases expression, decreases expression, affects binding (+1 more)	10
T0901317	affects binding, decreases reaction, affects cotreatment, increases expression, increases activity (+1 more)	9
Lithocholic Acid	affects binding, increases activity, increases expression, increases localization, increases reaction (+1 more)	9
Endosulfan	affects cotreatment, increases expression, increases reaction, decreases expression, affects binding (+1 more)	8
Phenytoin	increases expression, increases reaction, decreases reaction, increases activity, affects activity (+2 more)	8
Paclitaxel	decreases response to substance, affects binding, decreases reaction, increases reaction, increases activity (+1 more)	8
hyperforin	increases activity, increases reaction, affects cotreatment, increases response to substance, affects binding (+4 more)	7
propiconazole	affects binding, increases activity, increases expression	7
Pregnenolone Carbonitrile	increases expression, increases reaction, decreases reaction, increases activity	7
Triclosan	affects binding, increases activity, decreases expression	7
Cyclosporine	increases expression, affects expression, affects cotreatment, decreases expression	7
cypermethrin	affects binding, increases activity, increases expression	6
fenvalerate	affects binding, increases activity	6
Resveratrol	decreases reaction, decreases uptake, increases expression, affects binding, increases activity (+1 more)	6
Benzo(a)pyrene	increases activity, increases expression, decreases expression, increases methylation, affects cotreatment (+4 more)	6
DDT	affects binding, increases activity, affects cotreatment	6
Dieldrin	increases activity, affects binding, increases expression, increases reaction, affects cotreatment	6
Permethrin	affects binding, increases activity, increases expression	6
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects binding, increases activity, increases expression, increases reaction	5
enilconazole	decreases reaction, affects binding, increases activity, affects cotreatment	5
perfluorooctanoic acid	affects cotreatment, increases activity, affects binding, decreases expression, increases expression	5
bisphenol AF	affects binding, increases activity, decreases reaction	5
Rifaximin	increases expression, affects binding, decreases response to substance, decreases reaction, increases activity (+2 more)	5

ChEMBL screening assays

737 unique, capped per target: 477 binding, 201 admet, 30 functional, 29 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1012196	Binding	Displacement of [3H]SR12813 from human PXR by scintillation proximity competition binding assay	Synthesis and biological evaluation of hyperforin analogues. Part I. Modification of the enolized cyclohexanedione moiety. — J Nat Prod
CHEMBL1116220	Functional	Agonist activity at human PXR up to 50 uM by transactivation assay	Discovery of an oxybenzylglycine based peroxisome proliferator activated receptor alpha selective agonist 2-((3-((2-(4-chlorophenyl)-5-methyloxazol-4-yl)methoxy)benzyl)(methoxycarbonyl)amino)acetic acid (BMS-687453). — J Med Chem
CHEMBL1613993	ADMET	PUBCHEM_BIOASSAY: Luminescence-based counterscreen for activators of the Aryl Hydrocarbon Receptor (AHR): cell-based high throughput dose response screening assay for activators of the Pregnane X Receptor (PXR). (Class of assay: confirmator	PubChem BioAssay data set

Cellosaurus cell lines

10 cell lines: 7 cancer cell line, 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_6G77	HPLA-A3	Cancer cell line	Male
CVCL_A4T9	SEES3-1V human NR1I2, clone1	Embryonic stem cell	Male
CVCL_A4U0	SEES3-1V human NR1I2, clone2	Embryonic stem cell	Male
CVCL_A4U1	SEES3-1V human NR1I2, clone3	Embryonic stem cell	Male
CVCL_B6AS	HepaRG PXR KO	Cancer cell line	Female
CVCL_B6AT	HepaRG PXR/CAR KO	Cancer cell line	Female
CVCL_C0V7	HepG2 PXR-CYP3A4 clone 1	Cancer cell line	Male
CVCL_C0V8	HepG2 PXR-CYP3A4 clone 3	Cancer cell line	Male
CVCL_C0V9	HepG2 PXR-CYP3A4 clone 8	Cancer cell line	Male
CVCL_UK01	DPX2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00003398	PHASE4	COMPLETED	Bone Marrow Transplantation in Treating Patients With Hematologic Cancer
NCT00158041	PHASE4	COMPLETED	Subcutaneous Amifostine Safety Study
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00415103	PHASE4	COMPLETED	AMENO-2: Aprepitant Plus Palonosetron Versus Granisetron in the Prevention of Nausea and the Emesis Induced by Chemotherapy in Patients Treated With Haematopoietic Progenitors
NCT00854581	PHASE4	TERMINATED	Zidovudine, Interferon Alfa-2b, PEG-Interferon Alfa-2b in Patients With HTLV-I Associated Adult T-Cell Leukemia/Lymphoma
NCT01088750	PHASE4	COMPLETED	Surgery Alone or With CYC VBL and PRED or CVP Alone in Stage IA or IIA Nodular Lymphocyte-Predominant Hodgkin Lymphoma
NCT01658280	PHASE4	COMPLETED	Conventional Versus Ultrasound-guided Transbronchial Needle Aspiration for the Diagnosis of Hilar/Mediastinal Lymphadenopathies
NCT01841814	PHASE4	WITHDRAWN	Evolution of Bone Mineral Density (BMD) in Patients With Lymphoma Undergoing Chemotherapy
NCT01909934	PHASE4	COMPLETED	Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma
NCT02095951	PHASE4	COMPLETED	Preemptive Ethanol Lock Therapy in Pediatric Bloodstream Infection
NCT02347878	PHASE4	UNKNOWN	Self-control Trial to Evaluate the Role of Aprepitant in the Prophylaxis of Post-lumbar-punture-headache (PLPH)
NCT02805218	PHASE4	COMPLETED	PEG-rhG-CSF in Patients With Lymphoma Receiving Chemotherapy
NCT02905916	PHASE4	UNKNOWN	The Efficacy and Safety of PEG-rhG-CSF in Neutropenia After Chemotherapy
NCT02905942	PHASE4	UNKNOWN	PEG-rhG-CSF in Lymphoma Patients After Autologous Hematopoietic Stem Cell Transplantation
NCT02929615	PHASE4	UNKNOWN	Study of Standard and Individualized Treatment Model for Relapse and Refractory Lymphatic System Malignant Tumors
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03010579	PHASE4	UNKNOWN	Erythropoietin in the Treatment of Anemia After Autologous Hematopoietic Stem Cell Transplantation
NCT04349306	PHASE4	COMPLETED	Evaluate the Efficacy and Safety of Rasburicase (Fasturtec®) in the Prevention and Treatment of Hyperuricemia in Pediatric Patients With Non-Hodgkin’s Lymphoma and Acute Leukemia
NCT05170399	PHASE4	RECRUITING	Vaccine Responses in Patients With B Cell Malignancies
NCT05510544	PHASE4	UNKNOWN	Plerixafor for Poorly Mobilized Lymphoma
NCT06026995	PHASE4	UNKNOWN	Clinical Study on PEG-rhG-CSF in Mobilizing Autologous Hematopoietic Stem Cells
NCT06049134	PHASE4	ACTIVE_NOT_RECRUITING	Immunogenicity and Clinical Efficacy of 20-valent Pneumococcal Conjugate Vaccine (PCV20) in Lymphoma Survivors After Treatment With Anti-CD20 Therapy
NCT00002456	PHASE3	COMPLETED	Graft-Versus-Host Disease Prevention in Treating Patients Who Are Undergoing Bone Marrow Transplantation
NCT00002462	PHASE3	ACTIVE_NOT_RECRUITING	RT or No RT Following Chemotherapy in Treating Patients With Stage III/IV Hodgkin’s Disease
NCT00002495	PHASE3	COMPLETED	SWOG-9133 RT w/ or w/o Doxorubicin and Vinblastine in Stage I or Stage II Hodgkin’s Disease
NCT00002565	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Intermediate-Grade or Immunoblastic Non-Hodgkin’s Lymphoma
NCT00002576	PHASE3	COMPLETED	Combination Chemotherapy in Treating Older Patients With Intermediate- or High-Grade Non-Hodgkin’s Lymphoma
NCT00002618	PHASE3	COMPLETED	Combination Chemotherapy in Treating Pediatric Patients With Advanced-Stage Large Cell Lymphoma
NCT00002700	PHASE3	COMPLETED	Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Acute Lymphoblastic Leukemia
NCT00002742	PHASE3	COMPLETED	Antifungal Therapy for Fever and Neutropenia in Patients Receiving Treatment for Hematologic Cancer
NCT00002757	PHASE3	COMPLETED	TITLE:Less Intensive Therapy for Children With Non-Hodgkin’s Lymphoma
NCT00002766	PHASE3	COMPLETED	Comparison of Two Combination Chemotherapy Regimens in Treating Adults With Previously Untreated Leukemia or Lymphoma
NCT00002827	PHASE3	COMPLETED	Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin’s Disease
NCT00002835	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Lymphoma
NCT00002987	PHASE3	UNKNOWN	Combination Chemotherapy Given With Radiation Therapy or Radiation Therapy Alone in Treating Patients With Early-Stage Hodgkin’s Disease
NCT00002989	PHASE3	UNKNOWN	Combination Chemotherapy With or Without Idarubicin and Peripheral Stem Cell Transplantation in Treating Patients With Leukemia or Myelodysplastic Syndrome
NCT00003056	PHASE3	TERMINATED	Prevention of Graft-Versus-Host Disease in Patients With Advanced Leukemia or Lymphoma Who Are Eligible for Peripheral Stem Cell Transplantation
NCT00003150	PHASE3	COMPLETED	Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Older Patients With Non-Hodgkin’s Lymphoma
NCT00003152	PHASE3	TERMINATED	Chemotherapy Plus Interferon Alfa Alone or With Radiation Therapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage III or Stage IV Follicular Non-Hodgkin’s Lymphoma
NCT00003215	PHASE3	COMPLETED	Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Newly Diagnosed Aggressive Non-Hodgkin’s Lymphoma