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NR1H4 Gene

protein-coding   GIFtS: 66
GCID: GC12P100867

Nuclear Receptor Subfamily 1, Group H, Member 4

  See NR1H4-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Nuclear Receptor Subfamily 1, Group H, Member 41 2     HRR12 3
FXR2 3 5     RXR-Interacting Protein 142 3
RIP142 3 5     HRR-12
Farnesoid X-Activated Receptor2 3     Bile Acid Receptor2
Farnesol Receptor HRR-12 3     Farnesoid X Nuclear Receptor2
Retinoid X Receptor-Interacting Protein 142 3     Nuclear Receptor Subfamily 1 Group H Member 43
BAR2 3     

External Ids:    HGNC: 79671   Entrez Gene: 99712   Ensembl: ENSG000000125047   OMIM: 6038265   UniProtKB: Q96RI13   

Export aliases for NR1H4 gene to outside databases

Previous GC identifers: GC12P100078 GC12P100850 GC12P099370 GC12P097928


(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 NR1H4 Gene:
This gene encodes a ligand-activated transcription factor, which shares structural features in common with nuclear
hormone receptor family, such as a DNA-binding domain that targets the receptor to specific DNA sequences, and a
ligand-binding domain, which interacts directly with the ligand and contains a ligand-dependent transcriptional
activation domain. This protein functions as a receptor for bile acids, and when bound to bile acids, regulates
the expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants
encoding different isoforms have been described for this gene. (provided by RefSeq, Aug 2011)

GeneCards Summary for NR1H4 Gene:
NR1H4 (nuclear receptor subfamily 1, group H, member 4) is a protein-coding gene. Diseases associated with NR1H4 include atp8b1 deficiency, and cholestasis, intrahepatic, of pregnancy, 1. 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: NR1H4_HUMAN, Q96RI1
Function: Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid,
lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene
(CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the
intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by
directly recruiting histone methyltransferase CARM1 to this locus

summary for NR1H4 Gene:
Liver X receptors (LXRs) and farnesoid X receptors (FXRs) are members of the steroid analog-activated
nuclear receptor subfamily, which form heterodimers with members of the retinoid X receptor family. There
are two closely related isoforms of each of these enzymes; LXRalpha and LXRbeta, and FXRalpha and FXRbeta
(pseudogene in man). LXRalpha and FXRalpha expression is restricted to the liver, small intestine, kidney
and adrenal gland, whilst LXRbeta and FXRbeta are ubiquitously expressed. Despite acting on some of the same
target genes, including cholesterol 7alpha-hydroxylase (CYP7A1) and SREBP-1c, LXRs and FXRs have different
physiological roles. LXRs are involved in cholesterol homeostasis, inhibition of proinflammatory gene
expression in atherosclerosis and activation of innate immunity, whilst FXRs have a vital function in bile
acid homeostasis.

Gene Wiki entry for NR1H4 (Farnesoid X 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 at NCBI GenBank:
NC_000012.11  NT_029419.13  NC_018923.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the NR1H4 gene promoter:
         NF-1   MEF-2   Evi-1   HNF-4alpha1   MEF-2A   PPAR-gamma1   Chx10   PPAR-gamma2   aMEF-2   RSRFC4   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): NR1H4 promoter sequence
   Search Chromatin IP Primers for NR1H4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NR1H4


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

Entrez Gene cytogenetic band: 12q23.1   Ensembl cytogenetic band:  12q23.1   HGNC cytogenetic band: 12q23.1

NR1H4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NR1H4 gene location

GeneLoc information about chromosome 12         GeneLoc Exon Structure

GeneLoc location for GC12P100867:  view genomic region     (about GC identifiers)

Start:
100,867,486 bp from pter      End:
100,958,191 bp from pter
Size:
90,706 bases      Orientation:
plus 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, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: NR1H4_HUMAN, Q96RI1 (See protein sequence)
Recommended Name: Bile acid receptor  
Size: 486 amino acids; 55914 Da
Subunit: Heterodimer of NR1H4 and RXR. After activation by agonist binding, interacts with a coactivator, NCOA1 or
NCOA2 (By similarity). Interacts with CARM1 and SMARD1
Sequence caution: Sequence=BC144183; Type=Frameshift; Positions=156;
Selected PDB 3D structures from and Proteopedia for NR1H4 (see all 24):
1OSH (3D)        1OSK (3D)        3BEJ (3D)        3DCT (3D)        3DCU (3D)        3FLI (3D)    
Secondary accessions: A1L4K5 B7Z412 B7ZM06 F8VYG8 Q8NFP5 Q8NFP6 Q92943
Alternative splicing: 5 isoforms:  Q96RI1-3   Q96RI1-4   Q96RI1-1   Q96RI1-2   Q96RI1-5   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for NR1H4: NX_Q96RI1

Explore proteomics data for NR1H4 at MOPED

Post-translational modifications: 

  • Methylation may increase transactivation of target genes1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See NR1H4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (6 alternative transcripts): 
    NP_001193906.1  NP_001193907.1  NP_001193908.1  NP_001193921.1  NP_001193922.1  NP_005114.1  

    ENSEMBL proteins: 
     ENSP00000448506   ENSP00000376712   ENSP00000315442   ENSP00000448978   ENSP00000446760  
     ENSP00000446584   ENSP00000447149   ENSP00000188403   ENSP00000446861  
    Reactome Protein details: Q96RI1

    NR1H4 Human Recombinant Protein Products:

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    Novus Biologicals NR1H4 Proteins
    Novus Biologicals NR1H4 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for NR1H4 

     
    antibodies-online proteins for NR1H4 (4 products) 

     
    antibodies-online peptides for NR1H4

    NR1H4 Antibody Products:

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    Abcam antibodies for NR1H4
    Browse Antibodies at Cloud-Clone Corp.
    ThermoFisher Antibodies for NR1H4
    antibodies-online antibodies for NR1H4 (64 products) 

    NR1H4 Assay Products:

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    Browse CLIAs at Cloud-Clone Corp.
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    antibodies-online kits for NR1H4 (18 products) 


    (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: Farnesoid X receptor
    1H. Liver X 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 Q96RI1

    ProtoNet protein and cluster: Q96RI1

    2 Blocks protein domains:
    IPB000324 Vitamin D receptor signature
    IPB001723 Steroid hormone receptor signature


    UniProtKB/Swiss-Prot: NR1H4_HUMAN, Q96RI1
    Similarity: Belongs to the nuclear hormone receptor family. NR1 subfamily
    Similarity: Contains 1 nuclear receptor DNA-binding domain


    Find genes that share domains with NR1H4           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, 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, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: NR1H4_HUMAN, Q96RI1
    Function: Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid,
    lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene
    (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the
    intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by
    directly recruiting histone methyltransferase CARM1 to this locus

         Gene Ontology (GO): Selected molecular function terms (see all 20):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000980RNA polymerase II distal enhancer sequence-specific DNA binding IDA--
    GO:0001190RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription IDA--
    GO:0003677DNA binding ----
    GO:0003700sequence-specific DNA binding transcription factor activity TAS10334992
    GO:0003705RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity IDA--
         
    Find genes that share ontologies with NR1H4           About GenesLikeMe


    Phenotypes:
         2 GenomeRNAi human phenotypes for NR1H4:
     Downregulation of NF-kappaB pa  Downregulation of NF-kappaB pa 

         Selected MGI mutant phenotypes (inferred from 6 alleles(MGI details for Nr1h4) (see all 16):
     adipose tissue  behavior/neurological  cardiovascular system  cellular  digestive/alimentary 
     endocrine/exocrine gland  growth/size/body  hematopoietic system  homeostasis/metabolism  immune system 
     integument  liver/biliary system  mortality/aging  no phenotypic analysis  skeleton 

    Find genes that share phenotypes with NR1H4           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for NR1H4: Nr1h4tm1.2Auw Nr1h4tm1Kok Nr1h4tm1Gonz Nr1h4tm1.1Mbj

       genOway: Develop your customized and physiologically relevant rodent model for NR1H4

    Transcription Factor Targeting: 
    Targeting motifs: HOMER Transcription Factor Regulatory Elements motif viewer 
                                          Consensus sequence:  AGGTCANTGACCTN 

    miRNA
    Products:
        
    Block miRNA regulation of human, mouse, rat NR1H4 using miScript Target Protectors
    1 qRT-PCR Assays for microRNA that regulate NR1H4:
    hsa-miR-582-5p
    SwitchGear 3'UTR luciferase reporter plasmidNR1H4 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for NR1H4
    Predesigned siRNA for gene silencing in human, mouse, rat NR1H4

    Gene Editing
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    DNA2.0 Custom Protein Engineering Service for NR1H4

    Clone
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    OriGene ORF clones in mouse, rat for NR1H4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: NR1H4 (NM_005123)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for NR1H4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NR1H4

    Cell Line
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    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NR1H4


    (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
    NR1H4_HUMAN, Q96RI1: Nucleus (Probable)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus4
    peroxisome2
    extracellular1
    plasma membrane1

    Gene Ontology (GO): 3 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus ----
    GO:0005654nucleoplasm TAS--
    GO:0005719nuclear euchromatin IDA--

    Find genes that share ontologies with NR1H4           About GenesLikeMe


    (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 NR1H4 About   (see all 7)  
    See pathways by source

    SuperPathContained pathways About
    1Gene Expression
    Generic Transcription Pathway0.40
    Gene Expression0.40
    2Nuclear Receptor transcription pathway
    Nuclear Receptor transcription pathway0.67
    3Selected targets of HNF1
    Selected targets of HNF1
    4RXR and RAR heterodimerization with other nuclear receptor
    RXR and RAR heterodimerization with other nuclear receptor
    5Nuclear receptors in lipid metabolism and toxicity
    Nuclear receptors in lipid metabolism and toxicity


    Find genes that share SuperPaths with NR1H4           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    3 BioSystems Pathways for NR1H4
        Nuclear receptors in lipid metabolism and toxicity
    Drug Induction of Bile Acid Pathway
    RXR and RAR heterodimerization with other nuclear receptor

    1 Reactome Pathway for NR1H4
        Nuclear Receptor transcription pathway


    1 Kegg Pathway  (Kegg details for NR1H4):
        Bile secretion

        Pathway & Disease-focused RT2 Profiler PCR Arrays including NR1H4: 
              Lipoprotein Signaling & Cholesterol Metabolism in human mouse rat
              Nuclear Receptors & Coregulators in human mouse rat
              Fatty Liver in human mouse rat
              Molecular Toxicology PathwayFinder 384HT in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for NR1H4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for NR1H4 (Q96RI13 ENSP000003154424) via UniProtKB, MINT, STRING, and/or I2D (see all 54)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HIST1H4AP628053, ENSP000003529804I2D: score=1 STRING: ENSP00000352980
    HIST1H4BP628053I2D: score=1 
    HIST1H4CP628053I2D: score=1 
    HIST1H4DP628053I2D: score=1 
    HIST1H4EP628053I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 25):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000122negative regulation of transcription from RNA polymerase II promoter ISS--
    GO:0001080nitrogen catabolite activation of transcription from RNA polymerase II promoter IC--
    GO:0006109regulation of carbohydrate metabolic process IEA--
    GO:0006351transcription, DNA-templated ----
    GO:0006355regulation of transcription, DNA-templated ----

    Find genes that share ontologies with NR1H4           About GenesLikeMe



    (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 NR1H4
      Browse compounds at ApexBio 

    Compounds for NR1H4 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    GW 3965 hydrochlorideOrally active liver X receptor (LXR) agonist[405911-09-3]
    GW 4064Selective farnesoid X receptor (FXR) agonist[278779-30-9]
    Fexaramine Potent, selective farnesoid X receptor (FXR) agonist [574013-66-4]
    T 0901317Potent liver X receptor (LXR) agonist; also CAR inverse agonist[293754-55-9]

    2 HMDB Compounds for NR1H4    About this table
    CompoundSynonyms CAS #PubMed Ids
    Deoxycholic acid5b-Cholanic acid-3a,12a-diol (see all 14)83-44-3--
    Lithocholic acid(3a,5b)-3-hydroxy-cholan-24-oate (see all 5)434-13-9--

    3 DrugBank Compounds for NR1H4    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Chenodeoxycholic acidChenocholic acid (see all 3)474-25-9targetother10334992 20104269
    Fexaramine-- 574013-66-4target--17139284 17016423
    (8alpha,10alpha,13alpha,17beta)-17-[(4-hydroxyphenyl)carbonyl]androsta-3,5-diene-3-carboxylic acid-- --target--10592235

    5 IUPHAR Ligands for NR1H4 (Farnesoid X receptor)    About this table
    LigandTypeActionAffinityPubmed IDs
    GW4064
    AgonistAgonist7.8210956205
    ECDCA
    AgonistAgonist712166927
    fexaramine
    AgonistAgonist6.612718892
    guggulsterone
    AntagonistAntagonist5.7 - 612089353
    22R-hydroxycholesterol
    AgonistAgonist5.516371446

    Selected Novoseek inferred chemical compound relationships for NR1H4 gene (see all 43)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    gw 4064 97.3 55 12052824 (3), 15882126 (2), 19228886 (2), 11607932 (2) (see all 33)
    chenodeoxycholic acid 94 111 19913492 (3), 17975826 (2), 16522742 (2), 19059462 (2) (see all 55)
    guggulsterone 92.3 38 17135343 (4), 12705905 (3), 17054793 (2), 18519703 (2) (see all 17)
    6-ethylchenodeoxycholic acid 89.6 12 15317466 (1), 18029909 (1), 19864602 (1), 19418582 (1) (see all 5)
    androstane 88.6 39 19300246 (2), 17132852 (1), 18037906 (1), 20048746 (1) (see all 24)
    guggul 85.5 3 16428513 (1), 19102680 (1)
    lithocholic acid 81.6 21 12052824 (5), 16178789 (2), 16946559 (1), 10334993 (1) (see all 7)
    cholesterol 75.2 199 19136377 (4), 12704471 (4), 15558057 (3), 15962294 (3) (see all 94)
    apomine 73.5 1 11350890 (1)
    farnesol 67.1 16 10753967 (1), 17333335 (1), 8625436 (1), 16540091 (1) (see all 9)



    Find genes that share compounds with NR1H4           About GenesLikeMe



    (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,
    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, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for NR1H4 gene (6 alternative transcripts): 
    NM_001206977.1  NM_001206978.1  NM_001206979.1  NM_001206992.1  NM_001206993.1  NM_005123.3  

    Unigene Cluster for NR1H4:

    Nuclear receptor subfamily 1, group H, member 4
    Hs.282735  [show with all ESTs]
    Unigene Representative Sequence: NM_001206977
    9 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000548884(uc001thq.2 uc001thp.2 uc001thr.2 uc010svk.2 uc010svj.2 uc001ths.2 uc001tht.2)
    ENST00000392986 ENST00000321046 ENST00000549996 ENST00000546380 ENST00000548621
    ENST00000551379 ENST00000188403 ENST00000551184
    miRNA
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    Inhib. RNA
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    Primer
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      QuantiTect SYBR Green Assays in human, mouse, rat NR1H4
      QuantiFast Probe-based Assays in human, mouse, rat NR1H4

    Additional mRNA sequence: 

    AB307699.1 AF384555.1 AF478445.1 AF478446.1 AK296612.1 AK296647.1 AK312959.1 BC035654.1 
    BC071778.1 BC130573.1 BC144183.1 BC144184.1 BC144187.1 BX571749.1 HQ709175.1 U68233.1 

    6 DOTS entries:

    DT.213616  DT.100021403  DT.100746912  DT.40229020  DT.444293  DT.402350 

    Selected AceView cDNA sequences (see all 60):

    AF384555 AU104249 AA912967 AF478445 CB162215 AI075131 AF478446 BX102734 
    BC071778 AI051958 BX571749 AI628645 AI245366 BC035654 BG171220 BM545805 
    AI809578 CB111965 AI249049 AU099106 AA682292 T89438 AA862482 CD619886 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for NR1H4 (see all 7)    About this scheme

    ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4a · 4b · 4c · 4d ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14a · 14b
    SP1:                          -           -                       -     -                 -                                             
    SP2:                                                              -     -                                                               
    SP3:                                                                    -                 -                                             
    SP4:                                                                    -                                                               
    SP5:                                                                                                                                    


    ECgene alternative splicing isoforms for NR1H4

    (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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    NR1H4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    NR1H4 Expression
    About this image


    NR1H4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 5) fully expand
     
     Kidney (Urinary System)    fully expand to see all 3 entries
             Proximal Tubule Cells Proximal Tubule
             Proximal Tubule
     
     Epithelial Cells
             Proximal Tubule Cells Proximal Tubule
     
     Ovary (Reproductive System)
             Granulosa Cells Primary Follicle
     
     Adipose (Muscoskeletal System)
             HyStem+BMP4-induced 7SMOO32 cells
     
     Liver (Hepatobiliary System)
    NR1H4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    NR1H4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.282735
        Pathway & Disease-focused RT2 Profiler PCR Arrays including NR1H4: 
              Lipoprotein Signaling & Cholesterol Metabolism in human mouse rat
              Nuclear Receptors & Coregulators in human mouse rat
              Fatty Liver in human mouse rat
              Molecular Toxicology PathwayFinder 384HT in human mouse rat

    Primer
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NR1H4

    (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 NR1H4 gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Nr1h41 , 5 nuclear receptor subfamily 1, group H, member 41, 5 86.21(n)1
    92.8(a)1
      10 (44.98 cM)5
    201861  NM_001163700.11  NP_001157172.11 
     894542345 
    chicken
    (Gallus gallus)
    Aves NR1H41 nuclear receptor subfamily 1, group H, member 4 77.9(n)
    82.47(a)
      373902  NM_204113.2  NP_989444.1 
    lizard
    (Anolis carolinensis)
    Reptilia NR1H46
    nuclear receptor subfamily 1, group H, member 4
    70(a)
    1 ↔ 1
    5(28594962-28632394)
    African clawed frog
    (Xenopus laevis)
    Amphibia MGC686932 hypothetical protein MGC68693 73.44(n)    AF456451.1 
    zebrafish
    (Danio rerio)
    Actinopterygii nr1h41 nuclear receptor subfamily 1, group H, member 4 65.94(n)
    67.03(a)
      436847  NM_001002574.1  NP_001002574.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta EcR3 imaginal disc eversion ecdysteroid
    hormone receptor
    36(a)     --


    ENSEMBL Gene Tree for NR1H4 (if available)
    TreeFam Gene Tree for NR1H4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for NR1H4 gene
    VDR2  PPARD2  RARG2  NR1I22  PPARA2  THRB2  RARA2  NR1D22  
    RARB2  RORA2  RORB2  RORC2  NR1D12  NR1I32  PPARG2  NR1H22  
    THRA2  NR1H32  
    11 SIMAP similar genes for NR1H4 using alignment to 8 protein entries:     NR1H4_HUMAN (see all proteins):
    DKFZp686P04237    HNF4G    VDR    NR1H3    NR1I3    NR1H2
    NR1B2    NR1I2    DKFZp686D1580    NR1i1    RARB

    Find genes that share paralogs with NR1H4           About GenesLikeMe


    1 Pseudogenes.org Pseudogene for NR1H4
    PGOHUM00000261311


    (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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    Selected SNPs for NR1H4 (see all 1746)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 12 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs725156951,2
    C--97950787(+) AATCA-/AT/TA 
            
    AAACA
    4 -- int10--------
    rs557448641,2
    C--97960603(+) ACACAG/CACAGA 6 -- int11Minor allele frequency- C:0.50WA 2
    rs357371,2
    C,F,A--98011027(-) TTTTTC/G/TTTTGA 6 -- int1 trp35NA WA CSA 10
    rs2013376121,2
    --98011027(+) TCAAA-/GAAAAA 6 -- int10--------
    rs2001872831,2
    --98011038(+) AAAAA-/CAAAAA 6 -- int10--------
    rs113277861,2
    C--98011826(+) TCACAT/-GGTGA 6 -- int12Minor allele frequency- -:0.25NA CSA 4
    rs1866414051,2
    C--100704898(+) AAATAA/GTAACA 4 -- us2k10--------
    rs1912920921,2
    C--100704930(+) TCTGTA/GTGTCA 4 -- us2k10--------
    rs1169893831,2
    C,F--100705070(+) GGTCAC/TACAGC 4 -- us2k11Minor allele frequency- T:0.03EA 120
    rs1436193971,2
    --100705109(+) CCAGCC/TGGTCC 4 -- us2k10--------

    HapMap Linkage Disequilibrium report for NR1H4 (100867486 - 100958191 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 5 variations for NR1H4:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2673448CNV Deletion23128226
    nsv455700CNV Loss19166990
    dgv1484n71CNV Gain21882294
    nsv899470CNV Gain21882294
    nsv442285CNV CNV18776908

    Human Gene Mutation Database (HGMD): NR1H4
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing NR1H4
    DNA2.0 Custom Variant and Variant Library Synthesis for NR1H4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 603826    OMIM disorders: --

    10 diseases for NR1H4:    
    About MalaCards
    atp8b1 deficiency    cholestasis, intrahepatic, of pregnancy, 1    xanthomatosis    biliary tract disease
    intrahepatic cholestasis of pregnancy    fragile x syndrome    cerebrotendinous xanthomatosis    intrahepatic cholestasis
    cholestasis    atherosclerosis

    4 diseases from the University of Copenhagen DISEASES database for NR1H4:
    Cholestasis     Liver disease     Atherosclerosis     Diabetes mellitus

    Find genes that share disorders with NR1H4           About GenesLikeMe

    Selected Novoseek inferred disease relationships for NR1H4 gene (see all 28)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    byler disease 80.9 14 19381753 (4), 16628629 (2), 19027009 (1), 16819395 (1)
    cholestasis 76.7 29 19027009 (2), 19300246 (2), 15317749 (2), 16178789 (2) (see all 12)
    cholestasis intrahepatic 73.5 15 14988830 (2), 17681172 (1), 16819395 (1), 19490418 (1) (see all 8)
    dyslipidemia 54.8 10 19136377 (2), 15893927 (1), 18047847 (1), 18311660 (1)
    liver diseases 50.4 8 19187229 (1), 18668687 (1), 14992012 (1), 16706681 (1) (see all 6)
    biliary cirrhosis primary 48.6 2 15703646 (1), 19300246 (1)
    fragile x syndrome 45.9 2 8668200 (2)
    hypercholesterolemia 44 15 18948497 (2), 19136377 (1), 12704471 (1), 16905319 (1)
    atherosclerosis 39.6 8 20041971 (2), 17495603 (2), 17519356 (1), 18311660 (1) (see all 6)
    biliary atresia 39.4 2 16628629 (1), 15922475 (1)

    Genetic Association Database (GAD): NR1H4
    Human Genome Epidemiology (HuGE) Navigator: NR1H4 (13 documents)

    Export disorders for NR1H4 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 NR1H4 gene, integrated from 10 sources (see all 473):
    (articles sorted by number of sources associating them with NR1H4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Identification of a nuclear receptor for bile acids. (PubMed id 10334992)1, 2, 7, 9 Makishima M.... Shan B. (Science 1999)
    2. Functional variants of the central bile acid sensor FXR identified in intrahepatic cholestasis of pregnancy. (PubMed id 17681172)1, 4, 9 Van Mil S.W....Williamson C. (Gastroenterology 2007)
    3. Ligand-dependent activation of the farnesoid X-receptor directs arginine methylation of histone H3 by CARM1. (PubMed id 15471871)1, 2, 9 Ananthanarayanan M....Walsh M.J. (J. Biol. Chem. 2004)
    4. High frequency of a retinoid X receptor gamma gene variant in familial combined hyperlipidemia that associates with atherogenic dyslipidemia. (PubMed id 17272748)1, 4, 9 Nohara A....Mabuchi H. (Arterioscler. Thromb. Vasc. Biol. 2007)
    5. Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. (PubMed id 12815072)1, 2, 9 Holt J.A....Jones S.A. (Genes Dev. 2003)
    6. Bile acids: natural ligands for an orphan nuclear receptor. (PubMed id 10334993)1, 2, 9 Parks D.J....Lehmann J.M. (Science 1999)
    7. A common polymorphism in the ABCB11 gene is associated with advanced fibrosis in hepatitis C but not in non-alcoholic fatty liver disease. (PubMed id 20883210)1, 4 Iwata R....Geier A. (Clin. Sci. 2011)
    8. Genetic susceptibility to distinct bladder cancer subphenotypes. (PubMed id 19692168)1, 4 Guey L.T....Malats N. (Eur. Urol. 2010)
    9. Genetic risk factors for hepatopulmonary syndrome in patients with advanced liver disease. (PubMed id 20346360)1, 4 Roberts K.E....Fallon M.B. (Gastroenterology 2010)
    10. Common genetic variation in multiple metabolic pathways influences susceptibility to low HDL-cholesterol and coronary heart disease. (PubMed id 20855565)1, 4 Peloso G.M....Brousseau M.E. (J. Lipid Res. 2010)

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

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

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 9971 HGNC: 7967 AceView: NR1H4 Ensembl:ENSG00000012504 euGenes: HUgn9971
    ECgene: NR1H4 Kegg: 9971 H-InvDB: NR1H4

    (According to HUGE)
    About This Section

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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)
    About This Section

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    NameDescription
    PharmGKB entry for NR1H4 Pharmacogenomics, SNPs, Pathways
    Wikipedia http://en.wikipedia.org/wiki/Farnesoid_X_receptor

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for NR1H4 gene:
    Search GeneIP for patents involving NR1H4

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



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