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Set Analyses:

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NR1I3 Gene

protein-coding GIFtS: 63
GCID: GC01M161199

Nuclear Receptor Subfamily 1, Group I, Member 3

See related diseases
at

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Nuclear Receptor Subfamily 1, Group I, Member 3¹ ²		Constitutive Active Receptor²
Constitutive Androstane Receptor¹ ² ³		Constitutive Androstane Nuclear Receptor Variant 2²
CAR² ³ ⁵		Constitutive Androstane Nuclear Receptor Variant 3²
Constitutive Activator Of Retinoid Response² ³		Constitutive Androstane Nuclear Receptor Variant 4²
Constitutive Active Response² ³		Constitutive Androstane Nuclear Receptor Variant 5²
Orphan Nuclear Receptor MB67² ³		Nuclear Receptor Subfamily 1 Group I Member 3²
MB67² ⁵		Orphan Nuclear Hormone Receptor²
CAR1²

External Ids:	HGNC: 7969¹	Entrez Gene: 9970²	Ensembl: ENSG00000143257⁷	OMIM: 603881⁵	UniProtKB: Q14994³

Export aliases for NR1I3 gene to outside databases

Previous GC identifers: GC01M158910 GC01M156931 GC01M157978 GC01M158416 GC01M158012 GC01M159466 GC01M132556

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for NR1I3 Gene:

This gene encodes a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and

endobiotic metabolism. The protein binds to DNA as a monomer or a heterodimer with the retinoid X receptor and

regulates the transcription of target genes involved in drug metabolism and bilirubin clearance, such as

cytochrome P450 family members. Unlike most nuclear receptors, this transcriptional regulator is constitutively

active in the absence of ligand but is regulated by both agonists and inverse agonists. Ligand binding results in

translocation of this protein to the nucleus, where it activates or represses target gene transcription. These

ligands include bilirubin, a variety of foreign compounds, steroid hormones, and prescription drugs. Multiple

transcript variants encoding different isoforms have been found for this gene. (provided by RefSeq, Jul 2008)

GeneCards Summary for NR1I3 Gene:

NR1I3 (nuclear receptor subfamily 1, group I, member 3) is a protein-coding gene. Diseases associated with NR1I3 include biliary tract disease, and familial hypocalciuric hypercalcemia. GO annotations related to this gene include transcription coactivator activity and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is VDR.

UniProtKB/Swiss-Prot: NR1I3_HUMAN, Q14994

Function: Binds and transactivates the retinoic acid response elements that control expression of the retinoic

acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element

module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element

summary for NR1I3 Gene:

Vitamin D receptors (VDRs) are members of the NR1I family, which also includes pregnane X (PXR) and

constitutive androstane (CAR) receptors, that form heterodimers with members of the retinoid X receptor

family. VDR is expressed in the intestine, thyroid and kidney.

Gene Wiki entry for NR1I3 (Constitutive androstane receptor) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:

NC_000001.11 NT_004487.20 NC_018912.2

Regulatory elements:

Regulatory transcription factor binding sites in the NR1I3 gene promoter:
AP-1 ATF-2 MEF-2 CRE-BP1 PPAR-alpha CREB MEF-2A PPAR-gamma1 PPAR-gamma2 aMEF-2
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: NR1I3 promoter sequence

Search Chromatin IP Primers for NR1I3

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NR1I3

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

Entrez Gene cytogenetic band: 1q23.3 Ensembl cytogenetic band: 1q23.3 HGNC cytogenetic band: 1q23.3

NR1I3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NR1I3 gene location

GeneLoc information about chromosome 1 GeneLoc Exon Structure

GeneLoc location for GC01M161199: view genomic region (about GC identifiers)

Start:	161,199,456 bp from pter	End:	161,208,092 bp from pter
Size:	8,637 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: NR1I3_HUMAN, Q14994 (See protein sequence)

Recommended Name: Nuclear receptor subfamily 1 group I member 3

Size: 352 amino acids; 39942 Da

Subunit: Interacts with ECT2 (By similarity). Heterodimer of NR1I3 and RXR. Interacts with PSMC4. Directly

interacts with DNAJC7. The DNAJC7-NR1I3 complex may also include HSP90 (By similarity)

2 PDB 3D structures from and Proteopedia for NR1I3:

1XV9 (3D)

1XVP (3D)

Secondary accessions: E9PGH6 E9PH10 E9PHN4 F1D8Q0 F1D8Q1 Q0VAC9 Q4U0F0 Q5VTW5 Q5VTW6 Q6GZ68

Q6GZ77 Q6GZ78 Q6GZ83 Q6GZ84 Q6GZ85 Q6GZ87

Alternative splicing: 11 isoforms: Q14994-1 Q14994-2 Q14994-3 Q14994-4 Q14994-5 Q14994-6 Q14994-7 Q14994-8

Q14994-9 Q14994-10 Q14994-11

Explore the universe of human proteins at neXtProt for NR1I3: NX_Q14994

Explore proteomics data for NR1I3 at MOPED

Post-translational modifications:

Phosphorylated at Thr-38 by PKC, dephosphorylation of Thr-38 is required for nuclear translocation and activation¹

Modification sites at neXtProt

Modification sites at PhosphoSitePlus

See NR1I3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins (15 alternative transcripts):

NP_001070937.1 NP_001070938.1 NP_001070939.1 NP_001070940.1 NP_001070941.1 NP_001070942.1 NP_001070943.1 NP_001070944.1

NP_001070945.1 NP_001070946.1 NP_001070947.1 NP_001070948.1 NP_001070949.1 NP_001070950.1 NP_005113.1

ENSEMBL proteins:

ENSP00000425417 ENSP00000356962 ENSP00000407446 ENSP00000406493 ENSP00000399361

ENSP00000412672 ENSP00000424934 ENSP00000423666 ENSP00000356961 ENSP00000424834

ENSP00000422982 ENSP00000424345 ENSP00000427175 ENSP00000421374 ENSP00000423007

ENSP00000425607 ENSP00000356960 ENSP00000426016 ENSP00000421588 ENSP00000425900

ENSP00000426292 ENSP00000427600 ENSP00000356963 ENSP00000356965 ENSP00000356958

ENSP00000423089 ENSP00000427034 ENSP00000356959

Reactome Protein details: Q14994

NR1I3 Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells OriGene Protein Over-expression Lysate for NR1I3 OriGene Custom MassSpec OriGene Custom Protein Services for NR1I3
	GenScript Custom Purified and Recombinant Proteins Services for NR1I3
	Novus Biologicals NR1I3 Proteins Novus Biologicals NR1I3 Lysates
	Browse Sino Biological Recombinant Proteins Browse Sino Biological Cell Lysates
	Browse ProSpec Recombinant Proteins
	Browse Proteins at Cloud-Clone Corp.

NR1I3 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of NR1I3
	R&D Systems Antibodies for NR1I3 (CAR/NR1I3)
	OriGene Antibodies for NR1I3 OriGene Custom Antibody Services for NR1I3
	Novus Biologicals NR1I3 Antibodies
	Search for Antibodies for NR1I3 at Abcam
	Browse Antibodies at Cloud-Clone Corp.
	Search ThermoFisher Antibodies for NR1I3
	LSBio Antibodies in human, mouse, rat for NR1I3

NR1I3 Assay Products:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Assay Services for NR1I3
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for NR1I3
	Browse Enzo Life Sciences for kits & assays
	Browse ELISAs at Cloud-Clone Corp. Browse CLIAs at Cloud-Clone Corp.

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

NR: Nuclear hormone receptors

IUPHAR Guide to PHARMACOLOGY protein family classification: Constitutive androstane receptor

1I. Vitamin D receptor-like receptors

Selected InterPro protein domains (see all 6):

IPR013088 Znf_NHR/GATA

IPR008946 Nucl_hormone_rcpt_ligand-bd

IPR000536 Nucl_hrmn_rcpt_lig-bd_core

IPR001628 Znf_hrmn_rcpt

IPR001723 Str_hrmn_rcpt

Graphical View of Domain Structure for InterPro Entry Q14994

ProtoNet protein and cluster: Q14994

2 Blocks protein domains:

IPB000324 Vitamin D receptor signature

IPB001723 Steroid hormone receptor signature

UniProtKB/Swiss-Prot: NR1I3_HUMAN, Q14994

Domain: Composed by a short N-terminal domain followed by the DNA binding, hinge, and ligand binding/dimerization

domains

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

Similarity: Contains 1 nuclear receptor DNA-binding domain

NR1I3 for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: NR1I3_HUMAN, Q14994

Function: Binds and transactivates the retinoic acid response elements that control expression of the retinoic

acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element

module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element

Induction: By dexamethasone

Genatlas biochemistry entry for NR1I3:

nuclear receptor subfamily 1,group I,member 3,putatively heterodimerizing with RXR(s),expressed as several

isoforms

Gene Ontology (GO): Selected molecular function terms (see all 11): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003677	DNA binding	TAS	9783588
GO:0003700	sequence-specific DNA binding transcription factor activity	TAS	8020947
GO:0003707	steroid hormone receptor activity	--	--
GO:0003713	transcription coactivator activity	TAS	9783588
GO:0004879	ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity	TAS	8114692

NR1I3 for ontologies About GeneDecksing

Phenotypes:
6 MGI mutant phenotypes (inferred from 4 alleles) (MGI details for Nr1i3):

cellular	growth/size/body	homeostasis/metabolism	liver/biliary system	mortality/aging
reproductive system

NR1I3 for phenotypes About GeneDecksing

Animal Models:
MGI mouse knock-outs for NR1I3: Nr1i3^tm1.1Arte Nr1i3^tm1Dgen

inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for NR1I3

inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for NR1I3

genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for NR1I3

genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for NR1I3

miRNA Products:		Block miRNA regulation of human, mouse, rat NR1I3 using miScript Target Protectors
		Search for qRT-PCR Assays for microRNAs that regulate NR1I3
		Browse SwitchGear 3'UTR luciferase reporter plasmids

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for NR1I3
		Predesigned siRNA for gene silencing in human, mouse, rat NR1I3

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for NR1I3

Clone Products:		OriGene clones in human, mouse for NR1I3 (see all 72) OriGene ORF clones in mouse, rat for NR1I3 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 15): NR1I3 (NM_001077480)
		Sino Biological Human cDNA Clone for NR1I3
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for NR1I3
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NR1I3

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for NR1I3
		Browse ESI BIO Cell Lines and PureStem Progenitors for NR1I3

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NR1I3

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

NR1I3_HUMAN, Q14994: Nucleus. Cytoplasm. Cytoplasm, cytoskeleton. Note=Recruited to the cytoplasm by DNAJC7 (By

similarity)

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
cytoskeleton	5
nucleus	5
cytosol	2
peroxisome	2

About this image

Gene Ontology (GO): Selected cellular component terms (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	ISS	--
GO:0005654	nucleoplasm	TAS	--
GO:0005730	NOT nucleolus	IDA	--
GO:0005737	cytoplasm	ISS	--
GO:0005829	cytosol	IEA	--

NR1I3 for ontologies About GeneDecksing

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for NR1I3 About (see all 7)

See pathways by source

SuperPath

Contained pathways About

Nuclear Receptor transcription pathway

Nuclear Receptor transcription pathway

0.67

Nuclear Receptors

0.67

Gene Expression

Generic Transcription Pathway

0.40

Gene Expression

0.40

Selected targets of GCR alpha

Selected targets of GCR alpha

Nuclear receptors in lipid metabolism and toxicity

Nuclear receptors in lipid metabolism and toxicity

Glucocorticoid receptor regulatory network

Glucocorticoid receptor regulatory network

Pathways by source See SuperPaths
Show all pathways

4 BioSystems Pathways for NR1I3

	Nuclear Receptors
	Nuclear receptors in lipid metabolism and toxicity
	Drug Induction of Bile Acid Pathway
	Glucocorticoid receptor regulatory network

1 Reactome Pathway for NR1I3

Nuclear Receptor transcription pathway

1 PharmGKB Pathway for NR1I3

Carbamazepine Pathway, Pharmacokinetics

NR1I3 for pathways About GeneDecksing

Pathway & Disease-focused RT² Profiler PCR Array including NR1I3:

Nuclear Receptors & Coregulators in human mouse rat

Interactions:

GeneGlobe Interaction Network for NR1I3

STRING Interaction Network Preview (showing 5 interactants - click image to see 17)

Selected Interacting proteins for NR1I3 (Q14994³ ENSP00000356959⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 27)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
MED1	Q15648³, ENSP00000300651⁴	I2D: score=1 STRING: ENSP00000300651
PPARGC1A	Q9UBK2³, ENSP00000264867⁴	I2D: score=1 STRING: ENSP00000264867
RXRA	P19793³, ENSP00000419692⁴	I2D: score=2 STRING: ENSP00000419692
NCOA1	Q15788³, ENSP00000320940⁴	I2D: score=2 STRING: ENSP00000320940
HNF4A	P41235³, ENSP00000312987⁴	I2D: score=1 STRING: ENSP00000312987

About this table

Gene Ontology (GO): Selected biological process terms (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006351	transcription, DNA-templated	--	--
GO:0006355	regulation of transcription, DNA-templated	--	--
GO:0006367	transcription initiation from RNA polymerase II promoter	TAS	--
GO:0007165	signal transduction	TAS	8020947
GO:0010467	gene expression	TAS	--

NR1I3 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Enzo Life Sciences drugs & compounds for NR1I3

Browse compounds at ApexBio

Compounds for NR1I3 available from Tocris Bioscience About this table

Compound	Action	CAS #
EB 1089	Vitamin D receptor (VDR) agonist	[134404-52-7]
Calcipotriol	Vitamin D3 analog	[112965-21-6]
Alfacalcidol	Prodrug of vitamin D3 (Cat. No. 4156)	[41294-56-8]
Calcifediol	Prohormone of calcitriol (Cat. No. 2551). Major circulating form of vitamin D	[19356-17-3]
Calcitriol	Vitamin D receptor (VDR) agonist	[32222-06-3]

7 HMDB Compounds for NR1I3 About this table

Compound	Synonyms	CAS #	PubMed Ids
1-Butanol	1-Butanol (see all 10)	71-36-3	--
1-Hexanol	1-Hexyl alcohol (see all 30)	111-27-3	--
1-Pentanol	1-Pentol (see all 34)	71-41-0	--
Ethanol	1-Hydroxyethane (see all 57)	64-17-5	--
Isobutanol	1-Hydroxymethylpropane (see all 18)	78-83-1	--
Isopropyl alcohol	2-Propanol (see all 12)	67-63-0	--
Propyl alcohol	1-Hydroxypropane (see all 17)	71-23-8	--

2 DrugBank Compounds for NR1I3 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
(5BETA)-PREGNANE-3,20-DIONE	--	--	target	--	10592235
16,17-Androstene-3-Ol	--	7148-51-8	target	--	10592235

4 IUPHAR Ligands for NR1I3 (Constitutive androstane receptor) About this table

Ligand	Type	Action	Affinity	Pubmed IDs
CITCO	Agonist	Agonist	7.3	12611900
meclizine	Antagonist	Antagonist	7.16	15272053
pregnanedione	Agonist	Agonist	6.17	10748001
clotrimazole	Antagonist	Antagonist	6.16	10748001

Selected Novoseek inferred chemical compound relationships for NR1I3 gene (see all 73) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
androstane	99.2	707	11518807 (4), 12644700 (3), 16635107 (3), 11093784 (2) (see all 99)
citco	97.5	23	19588937 (2), 16099843 (1), 16929008 (1), 18332083 (1) (see all 10)
androstanol	91.6	12	15905360 (1), 16929008 (1), 17483497 (1), 18474683 (1) (see all 9)
tcpobop	87.4	34	15563456 (4), 16101572 (3), 18798339 (3), 18441373 (2) (see all 10)
androstenol	85	8	11457660 (3), 16929008 (1), 12114525 (1), 9783588 (1) (see all 5)
phenobarbital	82.5	133	19920082 (5), 10993889 (5), 17904175 (5), 11113125 (3) (see all 48)
dmes	82.4	14	19034627 (2), 16918318 (1), 18537574 (1), 19695866 (1) (see all 5)
cinacalcet	78.2	16	16189180 (4), 14696958 (2), 15794735 (1), 17373205 (1) (see all 7)
rifampicin	73.7	31	18786598 (3), 15919766 (3), 11181490 (2), 19588937 (2) (see all 16)
metofluthrin	72.1	3	19378387 (1), 19176367 (1)

NR1I3 for compounds About GeneDecksing

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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REFSEQ mRNAs for NR1I3 gene (15 alternative transcripts):

NM_001077469.2 NM_001077470.2 NM_001077471.2 NM_001077472.2 NM_001077473.2 NM_001077474.2 NM_001077475.2 NM_001077476.2

NM_001077477.2 NM_001077478.2 NM_001077479.2 NM_001077480.2 NM_001077481.2 NM_001077482.2 NM_005122.4

Unigene Cluster for NR1I3:

Nuclear receptor subfamily 1, group I, member 3

Hs.349642 [show with all ESTs]

Unigene Representative Sequence: AK303757

Selected Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 34):

ENST00000512372 ENST00000367983(uc001fzy.3) ENST00000488651 ENST00000464422

ENST00000437437 ENST00000479324 ENST00000442691 ENST00000412844 ENST00000428574

ENST00000505005 ENST00000508740 ENST00000367982 ENST00000506018 ENST00000508387

ENST00000504010 ENST00000511676 ENST00000502985 ENST00000512340

miRNA Products:		Block miRNA regulation of human, mouse, rat NR1I3 using miScript Target Protectors
		Search for qRT-PCR Assays for microRNAs that regulate NR1I3
		Browse SwitchGear 3'UTR luciferase reporter plasmids

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for NR1I3
		Predesigned siRNA for gene silencing in human, mouse, rat NR1I3

Clone Products:		OriGene clones in human, mouse for NR1I3 (see all 72) OriGene ORF clones in mouse, rat for NR1I3 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 15): NR1I3 (NM_001077480)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for NR1I3
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NR1I3

Primer Products:		OriGene qPCR primer pairs and template standards for NR1I3 OriGene qSTAR qPCR primer pairs in human, mouse for NR1I3
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat NR1I3
		QuantiTect SYBR Green Assays in human, mouse, rat NR1I3
		QuantiFast Probe-based Assays in human, mouse, rat NR1I3

Additional mRNA sequence:

AB307702.1 AK303757.1 AK303796.1 AK310773.1 AK316208.1 AY572806.1 AY572808.1 AY572810.1

AY572811.1 AY572812.1 AY572813.1 AY572816.1 AY572817.1 AY572818.1 AY572819.1 AY572820.1

AY572821.1 AY572822.1 AY572823.1 AY572824.1 AY572825.1 AY572827.1 BC069626.1 BC121120.1

BC121121.1 DQ022681.1 HQ692838.1 HQ692839.1 HQ692840.1 HQ692841.1 HQ709178.1

14 DOTS entries:

DT.121424716 DT.118470 DT.95212776 DT.75101308 DT.121424516 DT.121424730 DT.121424744 DT.121424507

DT.121424513 DT.121424575 DT.91855775 DT.75170204 DT.91931603 DT.97809200

Selected AceView cDNA sequences (see all 70):

AI262949 AY572825 AY572811 AY572816 BC069651 CB157668 AY572820 AW275372

AY572807 BM719939 AY572821 AY572818 AY572824 AV661397 AY572806 AY572815

AY572826 AY572810 AY572809 AY572819 AV652750 AV652691 AY572812 AY572823

GeneLoc Exon Structure

Selected Alternative Splicing Database (ASD) splice patterns (SP) for NR1I3 (see all 12) About this scheme

ExUns:	1	^	2a	·	2b	^	3	^	4a	·	4b	^	5	^	6	^	7a	·	7b	^	8a	·	8b	^	9	^	10
SP1:																					-				-
SP2:																	-								-
SP3:																	-		-		-				-
SP4:			-		-																				-
SP5:			-		-												-								-

ECgene alternative splicing isoforms for NR1I3

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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NR1I3 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: GCCCTCTTCT

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NR1I3 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 2) fully expand


Liver (Hepatobiliary System) fully expand to see all 2 entries
Perivenous Hepatocytes Liver Lobule

Kidney (Urinary System)

NR1I3 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

NR1I3 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.349642

UniProtKB/Swiss-Prot: NR1I3_HUMAN, Q14994

Tissue specificity: Predominantly expressed in liver

Pathway & Disease-focused RT² Profiler PCR Array including NR1I3:

Nuclear Receptors & Coregulators in human mouse rat

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

Orthologs for NR1I3 gene from Selected species (see all 10) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Nr1i3^{1 , 5}	nuclear receptor subfamily 1, group I, member 3^{1, 5}	80.75(n)¹ 74.71(a)¹		1 (79.21 cM)⁵ 12355¹ NM_009803.5¹ NP_033933.2¹ 171213970⁵
chicken (Gallus gallus)	Aves	NR1I3¹	nuclear receptor subfamily 1, group I, member 3	62.5(n) 57.56(a)		395439 NM_204702.1 NP_990033.1
lizard (Anolis carolinensis)	Reptilia	NR1I3⁶	nuclear receptor subfamily 1, group I, member 3	40(a)	1 ↔ 1	AAWZ02038821(3457-10280)
fruit fly (Drosophila melanogaster)	Insecta	EcR⁶	Ecdysone receptor	12(a)	1 → many	2R(1975378-2056592)

ENSEMBL Gene Tree for NR1I3 (if available)
TreeFam Gene Tree for NR1I3 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for NR1I3 gene

VDR² PPARD² RARG² NR1I2² PPARA² THRB² RARA² NR1H4²

NR1D2² RARB² RORA² RORB² RORC² NR1D1² PPARG² NR1H2²

THRA² NR1H3²

Selected SIMAP similar genes for NR1I3 using alignment to 22 protein entries: NR1I3_HUMAN (see all proteins) (see all similar genes):

THRB NR3C2 HNF4alpha NR3C4 AR VDR

ESR2 NR5A2 ERRgamma ESRRG RXRB NR3C1

RORA ESR1 NR1C3 NR4A1 PPARG NR2A2

NR1I3 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 1 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs199948971^1,2		--	132560554(+)	`ATATA-/TATG TGTGT`	15	--	int¹		0	--	--	--	--
rs112168438^1,2	C,F	--	161202024(+)	`ACCCAG/CCTTGG`	15	--	int¹		1		WA	2
rs3003593^1,2	C,H	--	161203627(+)	`TATAtA/Gtgtgt`	15	--	int¹		0	--	--	--	--
rs11265569^1,2	C,A,H	--	161203669(+)	`tgtgtA/Gtgtgt`	15	--	int¹		0	--	--	--	--
rs12402656^1,2	A,H	--	161203675(+)	`tgtgtA/GtGtat`	15	--	int¹		0	--	--	--	--
rs113093711^1,2	C	--	161206516(+)	`TGTGG-/TTTTCT TTTTC`	15	--	cds¹		1		CSA	2
rs34795024^1,2	C	--	161208668(+)	`AAAAAA/-GAGAG`	15	--	us2k¹		1		NA	2
rs111781352^1,2	C,F	--	167695278(+)	`GCCCTC/TCTCAG`	15	--	ds500¹		3		CSA WA	122
rs150543962^1,2	C	--	167695425(+)	`CCCCCA/GGCACC`	15	--	ds500¹		0	--	--	--	--
rs35937139^1,2	C	--	167695639(-)	`GAAGCA/TCAGAA`	15	--	ds500¹		1		--	194

HapMap Linkage Disequilibrium report for NR1I3 (161199456 - 161208092 bp)

Structural Variations
Database of Genomic Variants (DGV) variations for NR1I3: --
Human Gene Mutation Database (HGMD): NR1I3

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing NR1I3

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 603881 OMIM disorders: --

Selected diseases for NR1I3 (see all 49):
About MalaCards

biliary tract disease familial hypocalciuric hypercalcemia hypercalcemia humoral hypercalcemia of malignancy

primary hyperparathyroidism acute porphyria uremia hyperparathyroidism

hypoparathyroidism bilirubin metabolic disorder nephrocalcinosis cholestasis

nephrolithiasis neonatal jaundice gastrinoma porphyria

intrahepatic cholestasis of pregnancy zellweger syndrome leukopenia rickets

3 diseases from the University of Copenhagen DISEASES database for NR1I3:

Cholestasis Bilirubin metabolic disorder Neonatal jaundice

NR1I3 for disorders About GeneDecksing

Selected Novoseek inferred disease relationships for NR1I3 gene (see all 39) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
hyperparathyroidism secondary	73.2	15	16189180 (2), 11033758 (1), 16919492 (1), 12830754 (1) (see all 13)
nshpt	61.3	3	11033758 (1), 9507434 (1)
hyperparathyroidism	60.1	11	15658669 (2), 8675635 (1), 17018434 (1), 9011580 (1) (see all 9)
hypercalcemia	58.6	22	11033758 (2), 16189180 (2), 16603723 (2), 18492387 (1) (see all 9)
hyperparathyroidism primary	57.2	11	11134144 (2), 16189180 (2), 8675635 (1), 9509247 (1) (see all 5)
parathyroid hyperplasia	54.9	4	12469914 (2), 15888568 (1)
cholestasis	54.4	8	16565602 (2), 16101572 (1), 19300246 (1), 16025508 (1) (see all 5)
hypocalcemia	48.2	5	15507543 (1), 17018434 (1), 9757371 (1), 11701698 (1)
hypoparathyroidism	43.9	10	11701698 (3), 12940896 (1), 9757371 (1), 9768650 (1) (see all 7)
jaundice neonatal	43.5	3	12644704 (1), 19925451 (1)

Genetic Association Database (GAD): NR1I3
Human Genome Epidemiology (HuGE) Navigator: NR1I3 (7 documents)

Export disorders for NR1I3 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for NR1I3 gene, integrated from 10 sources (see all 517):
(articles sorted by number of sources associating them with NR1I3)

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

A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements. (PubMed id 8114692)^{1, 2, 3} Baes M.... Moore D.D. (Mol. Cell. Biol. 1994)
Dephosphorylation of threonine 38 is required for nuclear translocation and activation of human xenobiotic receptor CAR (NR1I3). (PubMed id 19858220)^{1, 2, 9} Mutoh S.... Negishi M. (J. Biol. Chem. 2009)
Expression of constitutive androstane receptor splice variants in human tissues and their functional consequences. (PubMed id 15194709)^{1, 2, 9} Lamba J.K.... Schuetz E.G. (J. Pharmacol. Exp. Ther. 2004)
PXR, CAR and HNF4alpha genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients. (PubMed id 17876342)^{1, 4, 9} Hor S.Y....Tan T. (Pharmacogenomics J. 2008)
Lack of association of single-nucleotide polymorphisms in pregnane X receptor, hepatic nuclear factor 4alpha, and constitutive androstane receptor with docetaxel pharmacokinetics. (PubMed id 18056193)^{1, 4, 9} Tham L.S....Goh B.C. (Clin. Cancer Res. 2007)
A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer. (PubMed id 15610735)^{1, 2, 9} Xu R.X....Moore J.T. (Mol. Cell 2004)
Association of genetic polymorphisms in SLCO1B3 and ABCC2 with docetaxel-induced leukopenia. (PubMed id 18294295)^{1, 4} Kiyotani K....Nakamura Y. (Cancer Sci. 2008)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S.... Malek J. (Genome Res. 2004)
Twenty-six novel single nucleotide polymorphisms and their frequencies of the NR1I3 (CAR) gene in a Japanese population. (PubMed id 15618763)^{1, 2} Ikeda S.... Sawada J. (Drug Metab. Pharmacokinet. 2003)
A component of the 26S proteasome binds on orphan member of the nuclear hormone receptor superfamily. (PubMed id 8603043)^{1, 2} Choi H.S.... Moore D.D. (J. Steroid Biochem. Mol. Biol. 1996)

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

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

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 9970	HGNC: 7969	AceView: NR1I3	Ensembl:ENSG00000143257	euGenes: HUgn9970
ECgene: NR1I3	H-InvDB: NR1I3

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for NR1I3	Pharmacogenomics, SNPs, Pathways

Intellectual Property for NR1I3 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for NR1I3 gene:
Search GeneIP for patents involving NR1I3

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

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NR1I3 Gene

Nuclear Receptor Subfamily 1, Group I, Member 3

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Fatty Liver
Hypocalcemia
Melanoma
parathyroid hyperplasia
Hyperplasia
Astrocytoma
Cholestasis Intrahepatic
Hyperparathyroidism
Bone Diseases
Liver diseases
Breast Cancer
Osteoporosis
Hyperparathyroidism Secondary
Jaundice Neonatal
HEPATOCELLULAR CARCINOMA
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RENAL DISEASE
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genetic disorder
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NR1I3 Gene

Nuclear Receptor Subfamily 1, Group I, Member 3

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