This gene encodes a ligand-activated transcription factor that shares structural features in common with nuclear hormone receptor family members. This protein functions as a receptor for bile acids, and when bound to bile acids, binds to DNA and regulates the expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants encoding di... See more...

Aliases for NR1H4 Gene

Aliases for NR1H4 Gene

  • Nuclear Receptor Subfamily 1 Group H Member 4 2 3 4 5
  • Bile Acid Receptor 2 3 4
  • Retinoid X Receptor-Interacting Protein 14 3 4
  • Farnesoid X-Activated Receptor 3 4
  • RXR-Interacting Protein 14 3 4
  • Farnesol Receptor HRR-1 3 4
  • RIP14 3 4
  • HRR1 3 4
  • BAR 3 4
  • FXR 3 4
  • Nuclear Receptor Subfamily 1, Group H, Member 4 2
  • Farnesoid X Nuclear Receptor 3
  • Farnesoid X Receptor 2
  • HRR-1 3
  • PFIC5 3

External Ids for NR1H4 Gene

Previous GeneCards Identifiers for NR1H4 Gene

  • GC12P100078
  • GC12P100850
  • GC12P099370
  • GC12P097928
  • GC12P100867

Summaries for NR1H4 Gene

Entrez Gene Summary for NR1H4 Gene

  • This gene encodes a ligand-activated transcription factor that shares structural features in common with nuclear hormone receptor family members. This protein functions as a receptor for bile acids, and when bound to bile acids, binds to DNA and regulates the expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Feb 2016]

GeneCards Summary for NR1H4 Gene

NR1H4 (Nuclear Receptor Subfamily 1 Group H Member 4) is a Protein Coding gene. Diseases associated with NR1H4 include Cholestasis, Progressive Familial Intrahepatic, 5 and Cholestasis, Progressive Familial Intrahepatic, 1. Among its related pathways are Cytochrome P450 - arranged by substrate type and Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha). Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity. An important paralog of this gene is NR1H3.

UniProtKB/Swiss-Prot Summary for NR1H4 Gene

  • Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved innate immune response (PubMed:10334992, PubMed:10334993, PubMed:21383957, PubMed:22820415). The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in which the monomers are spaced by 1 nucleotide (IR-1) but also to tandem repeat DR1 sites with lower affinity, and can be activated by either FXR or RXR-specific ligands. It is proposed that monomeric nuclear receptors such as NR5A2/LRH-1 bound to coregulatory nuclear responsive element (NRE) halfsites located in close proximity to FXREs modulate transcriptional activity (By similarity). In the liver activates transcription of the corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1 (involved in BA synthesis) implicating at least in part histone demethylase KDM1A resulting in epigenomic repression, and SLC10A1/NTCP (involved in hepatic uptake of conjugated BAs). Activates transcription of the repressor MAFG (involved in regulation of BA synthesis) (By similarity). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine) (PubMed:12754200, PubMed:15471871, PubMed:17895379). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine) (PubMed:10514450, PubMed:15239098, PubMed:16269519). In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression (PubMed:12815072, PubMed:19085950). The function also involves the coordinated induction of hepatic KLB/beta-klotho expression (By similarity). Regulates transcription of liver UGT2B4 and SULT2A1 involved in BA detoxification; binding to the UGT2B4 promoter seems to imply a monomeric transactivation independent of RXRA (PubMed:12806625, PubMed:16946559). Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, PPARA (involved in beta-oxidation of fatty acids), VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly (PubMed:12660231, PubMed:12554753, PubMed:15337761). Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance) (PubMed:11579204). Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element (PubMed:11927623, PubMed:21804189). Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase) (PubMed:12891557). Involved in glucose homeostasis by modulating hepatic gluconeogenesis through activation of NR0B2/SHP-mediated repression of respective genes. Modulates glycogen synthesis (inducing phosphorylation of glycogen synthase kinase-3) (By similarity). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance (PubMed:20447400). Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier (By similarity). Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells (PubMed:21242261). Mediates trans-repression of TLR4-induced cytokine expression; the function seems to require its sumoylation and prevents N-CoR nuclear receptor corepressor clearance from target genes such as IL1B and NOS2 (PubMed:19864602). Involved in the TLR9-mediated protective mechanism in intestinal inflammation. Plays an anti-inflammatory role in liver inflammation; proposed to inhibit proinflammatory (but not antiapoptotic) NF-kappa-B signaling) (By similarity).
  • [Isoform 1]: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA.
  • [Isoform 2]: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA), NR0B2/SHP (inducible by unconjugated CDCA DCA and ACA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; not inducible by taurine- and glycine-amidated CDCA.
  • [Isoform 3]: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA.
  • [Isoform 4]: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, ACA and DCA), NR0B2/SHP (inducible by unconjugated CDCA, ACA and DCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; most efficient isoform compared to isoforms 1 to 3; not inducible by taurine- and glycine-amidated CDCA.

Tocris 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; alpha and beta.

Gene Wiki entry for NR1H4 Gene

Additional gene information for NR1H4 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NR1H4 Gene

Genomics for NR1H4 Gene

GeneHancer (GH) Regulatory Elements for NR1H4 Gene

Promoters and enhancers for NR1H4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J100473 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE 500.7 +1.5 1519 4.1 EP300 POLR2G NCOR1 TCF7 ZBTB25 TGIF2 ZBTB7A SKI TEAD1 TBX3 HSALNG0093453 NR1H4 ENSG00000271177 lnc-DEPDC4-4
GH12J100500 Promoter/Enhancer 1.1 EPDnew ENCODE dbSUPER 511.5 +29.9 29877 5.7 FOXA2 ZBTB33 RBM22 JUND RAD21 RXRA MAX HNF4A REST MAFK NR1H4 ENSG00000271177 lnc-DEPDC4-4 HSALNG0093453
GH12J100445 Enhancer 1 Ensembl ENCODE 11.6 -28.3 -28258 0.9 KDM6A ZBTB25 TEAD1 FOXA2 KMT2B NR2F2 CEBPB SAP130 MBD1 ZBTB33 NR1H4 HSALNG0093451 piR-33735-022
GH12J100492 Enhancer 0.7 ENCODE dbSUPER 12.1 +21.8 21810 5.9 NR2F2 FOS RBM22 RXRA EGR2 NR3C1 SP1 NR1H4 SLC17A8 GAS2L3 HSALNG0093453 lnc-DEPDC4-4 ENSG00000271177
GH12J100527 Enhancer 0.7 Ensembl ENCODE 11.4 +54.9 54904 2.9 TCF12 FOSL2 NR3C1 FOXA1 ATF3 REST SP1 NR1H4 SLC17A8 ENSG00000271177 lnc-DEPDC4-4 lnc-DEPDC4-3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NR1H4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NR1H4

Top Transcription factor binding sites by QIAGEN in the NR1H4 gene promoter:
  • aMEF-2
  • Chx10
  • Evi-1
  • HNF-4alpha1
  • MEF-2
  • MEF-2A
  • NF-1
  • PPAR-gamma1
  • PPAR-gamma2
  • RSRFC4

Genomic Locations for NR1H4 Gene

Genomic Locations for NR1H4 Gene
chr12:100,473,708-100,564,414
(GRCh38/hg38)
Size:
90,707 bases
Orientation:
Plus strand
chr12:100,867,486-100,958,191
(GRCh37/hg19)
Size:
90,706 bases
Orientation:
Plus strand

Genomic View for NR1H4 Gene

Genes around NR1H4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NR1H4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NR1H4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NR1H4 Gene

Proteins for NR1H4 Gene

  • Protein details for NR1H4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96RI1-NR1H4_HUMAN
    Recommended name:
    Bile acid receptor
    Protein Accession:
    Q96RI1
    Secondary Accessions:
    • A1L4K5
    • B7Z412
    • B7ZM06
    • F8VYG8
    • Q8NFP5
    • Q8NFP6
    • Q92943

    Protein attributes for NR1H4 Gene

    Size:
    486 amino acids
    Molecular mass:
    55914 Da
    Quaternary structure:
    • Heterodimer (via C-terminus) with RXRA (via DBD); the heterodimerization enhances the binding affinity for LXXLL motifs from coactivators (PubMed:23462506, PubMed:30275017). Binds DNA predominantly as a heterodimer with RXRA. After activation by agonist binding interacts with coactivators. Interacts with NCOA1, NCOA2, PPARGC1A, CARM1, SETD7, PRMT1, GPS2, SMARCA4 and MED1 (PubMed:15202934, PubMed:14684751, PubMed:15187081, PubMed:15471871, PubMed:15911693, PubMed:17895379, PubMed:18755856, PubMed:19805516, PubMed:23462506, PubMed:12718892, PubMed:12718893, PubMed:18621523, PubMed:18391212, PubMed:19410460, PubMed:19586769). Interacts with EP300 and SMARCD1 (By similarity). Interacts with XRCC5 and XRCC6; decreasing NR1H4/FXR transactivation activity towards ABCB11/BSEP (PubMed:19833092). Interacts with PAGR1 AND NCOA6; indicative for an association with an MLL2/MLL3 complex (ASCOM) (PubMed:19556342).
    Miscellaneous:
    • Ursodeoxycholic (UDCA), a natural agonist of FXR, is approved to treat primary biliary cirrhosis. However, effects are discussed controversial. UDCA is also used to dissolve (cholesterol) gallstones as alternative to surgery.
    • [Isoform 1]: Produced by alternative promoter usage.
    • [Isoform 2]: Produced by alternative splicing of isoform 1.
    • [Isoform 3]: Produced by alternative promoter usage.
    • [Isoform 4]: Produced by alternative splicing of isoform 3.
    • [Isoform 5]: Produced by alternative splicing of isoform 3.
    SequenceCaution:
    • Sequence=BC144183; Type=Frameshift; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for NR1H4 Gene

    Alternative splice isoforms for NR1H4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NR1H4 Gene

Post-translational modifications for NR1H4 Gene

  • Acetylated by EP300. Lys-227 as is the major acetylation site for EP300; the dynamicly regulated acetylation inhibits heterodimerization with RXRA and transactivation activity. Deacetylated by SIRT1.
  • Methylation may increase transactivation of target genes.
  • Phosphorylation by PKC/PRKCA increases transactivation activity by promoting association with PPARGC1A.
  • Sumoylated upon ligand binding.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for NR1H4 Gene

Domains & Families for NR1H4 Gene

Gene Families for NR1H4 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • FDA approved drug targets
  • Nuclear receptors
  • Predicted intracellular proteins
  • Transcription factors
  • Transporters

Protein Domains for NR1H4 Gene

Blocks:
  • Steroid hormone receptor signature
  • Vitamin D receptor signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for NR1H4 Gene

GenScript: Design optimal peptide antigens:
  • Nuclear receptor subfamily 1, group H, member 4, isoform CRA_a (B6ZGS9_HUMAN)
  • Farnesoid X nuclear receptor (F1DAL1_HUMAN)
  • Retinoid X receptor-interacting protein 14 (NR1H4_HUMAN)
  • NR1H4 protein (Q6IPQ7_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96RI1

UniProtKB/Swiss-Prot:

NR1H4_HUMAN :
  • Belongs to the nuclear hormone receptor family. NR1 subfamily.
Family:
  • Belongs to the nuclear hormone receptor family. NR1 subfamily.
genes like me logo Genes that share domains with NR1H4: view

Function for NR1H4 Gene

Molecular function for NR1H4 Gene

UniProtKB/Swiss-Prot Function:
Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved innate immune response (PubMed:10334992, PubMed:10334993, PubMed:21383957, PubMed:22820415). The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in which the monomers are spaced by 1 nucleotide (IR-1) but also to tandem repeat DR1 sites with lower affinity, and can be activated by either FXR or RXR-specific ligands. It is proposed that monomeric nuclear receptors such as NR5A2/LRH-1 bound to coregulatory nuclear responsive element (NRE) halfsites located in close proximity to FXREs modulate transcriptional activity (By similarity). In the liver activates transcription of the corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1 (involved in BA synthesis) implicating at least in part histone demethylase KDM1A resulting in epigenomic repression, and SLC10A1/NTCP (involved in hepatic uptake of conjugated BAs). Activates transcription of the repressor MAFG (involved in regulation of BA synthesis) (By similarity). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine) (PubMed:12754200, PubMed:15471871, PubMed:17895379). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine) (PubMed:10514450, PubMed:15239098, PubMed:16269519). In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression (PubMed:12815072, PubMed:19085950). The function also involves the coordinated induction of hepatic KLB/beta-klotho expression (By similarity). Regulates transcription of liver UGT2B4 and SULT2A1 involved in BA detoxification; binding to the UGT2B4 promoter seems to imply a monomeric transactivation independent of RXRA (PubMed:12806625, PubMed:16946559). Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, PPARA (involved in beta-oxidation of fatty acids), VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly (PubMed:12660231, PubMed:12554753, PubMed:15337761). Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance) (PubMed:11579204). Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element (PubMed:11927623, PubMed:21804189). Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase) (PubMed:12891557). Involved in glucose homeostasis by modulating hepatic gluconeogenesis through activation of NR0B2/SHP-mediated repression of respective genes. Modulates glycogen synthesis (inducing phosphorylation of glycogen synthase kinase-3) (By similarity). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance (PubMed:20447400). Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier (By similarity). Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells (PubMed:21242261). Mediates trans-repression of TLR4-induced cytokine expression; the function seems to require its sumoylation and prevents N-CoR nuclear receptor corepressor clearance from target genes such as IL1B and NOS2 (PubMed:19864602). Involved in the TLR9-mediated protective mechanism in intestinal inflammation. Plays an anti-inflammatory role in liver inflammation; proposed to inhibit proinflammatory (but not antiapoptotic) NF-kappa-B signaling) (By similarity).
UniProtKB/Swiss-Prot Function:
[Isoform 1]: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA.
UniProtKB/Swiss-Prot Function:
[Isoform 2]: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA), NR0B2/SHP (inducible by unconjugated CDCA DCA and ACA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; not inducible by taurine- and glycine-amidated CDCA.
UniProtKB/Swiss-Prot Function:
[Isoform 3]: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA.
UniProtKB/Swiss-Prot Function:
[Isoform 4]: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, ACA and DCA), NR0B2/SHP (inducible by unconjugated CDCA, ACA and DCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; most efficient isoform compared to isoforms 1 to 3; not inducible by taurine- and glycine-amidated CDCA.

Phenotypes From GWAS Catalog for NR1H4 Gene

Gene Ontology (GO) - Molecular Function for NR1H4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000976 transcription regulatory region sequence-specific DNA binding IBA 21873635
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IDA 23767959
GO:0000980 RNA polymerase II distal enhancer sequence-specific DNA binding IDA 21757002
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS,IDA 19274049
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IDA 21757002
genes like me logo Genes that share ontologies with NR1H4: view
genes like me logo Genes that share phenotypes with NR1H4: view

Human Phenotype Ontology for NR1H4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for NR1H4 Gene

MGI Knock Outs for NR1H4:

Animal Model Products

CRISPR Products

miRNA for NR1H4 Gene

miRTarBase miRNAs that target NR1H4
Targeted motifs for NR1H4 Gene
HOMER Transcription Factor Regulatory Elements motif NR1H4
  • Consensus sequence: AGGTCANTGACCTN Submotif: IR1 Cell Type: Liver

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NR1H4

Clone Products

No data available for Enzyme Numbers (IUBMB) and Transcription Factor Targets for NR1H4 Gene

Localization for NR1H4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NR1H4 Gene

Nucleus.
[Isoform 1]: Nucleus.
[Isoform 2]: Nucleus.
[Isoform 3]: Nucleus.
[Isoform 4]: Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NR1H4 gene
Compartment Confidence
nucleus 5
extracellular 3
peroxisome 3
plasma membrane 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
cytosol 2
lysosome 2
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NR1H4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005623 cell IEA --
GO:0005634 nucleus IBA 21873635
GO:0005654 nucleoplasm TAS --
GO:0005719 nuclear euchromatin IDA 21757002
genes like me logo Genes that share ontologies with NR1H4: view

Pathways & Interactions for NR1H4 Gene

genes like me logo Genes that share pathways with NR1H4: view

SIGNOR curated interactions for NR1H4 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for NR1H4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II ISS 21757002
GO:0001080 nitrogen catabolite activation of transcription from RNA polymerase II promoter IC 21757002
GO:0001678 cellular glucose homeostasis IEA --
GO:0002376 immune system process IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
genes like me logo Genes that share ontologies with NR1H4: view

Drugs & Compounds for NR1H4 Gene

(34) Drugs for NR1H4 Gene - From: DrugBank, ApexBio, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
chenodeoxycholic acid Approved Pharma Antagonist, Full agonist, Agonist, Target, other 41
Obeticholic acid Approved Pharma Target, agonist 0
deoxycholic acid Approved Pharma Antagonist, Full agonist, Agonist, Target 49
cholic acid Approved Pharma Full agonist, Agonist, Target 0
Ursodeoxycholic acid Approved, Investigational Pharma Target 125

(22) Additional Compounds for NR1H4 Gene - From: IUPHAR, Novoseek, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
GW 4064
278779-30-9
ECDCA
Agonist

(3) Tocris Compounds for NR1H4 Gene

Compound Action Cas Number
27-Hydroxycholesterol LXR agonist; also ER partial agonist 20380-11-4
GW 4064 Selective farnesoid X receptor (FXR) agonist 278779-30-9
T 0901317 Potent liver X receptor (LXR) agonist; also CAR inverse agonist 293754-55-9

(7) ApexBio Compounds for NR1H4 Gene

Compound Action Cas Number
Chenodeoxycholic Acid 474-25-9
Guggulsterone 95975-55-6
GW4064 Non-steroidal FXR agonist,potent and selective 278779-30-9
Lithocholic Acid Activator of vitamin D receptor,PXR and FXR 434-13-9
Obeticholic Acid 459789-99-2
XL335 FXR agonist 629664-81-9
Z-Guggulsterone 39025-23-5
genes like me logo Genes that share compounds with NR1H4: view

Drug Products

Transcripts for NR1H4 Gene

mRNA/cDNA for NR1H4 Gene

6 REFSEQ mRNAs :
18 NCBI additional mRNA sequence :
11 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NR1H4

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NR1H4 Gene

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:
SP6: - - -
SP7: -

Relevant External Links for NR1H4 Gene

GeneLoc Exon Structure for
NR1H4

Expression for NR1H4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NR1H4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NR1H4 Gene

This gene is overexpressed in Liver (x25.2), Adrenal Gland (x7.1), Small Intestine - Terminal Ileum (x6.8), and Kidney - Cortex (x5.5).

Protein differential expression in normal tissues from HIPED for NR1H4 Gene

This gene is overexpressed in Bone marrow stromal cell (67.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for NR1H4 Gene



Protein tissue co-expression partners for NR1H4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NR1H4

SOURCE GeneReport for Unigene cluster for NR1H4 Gene:

Hs.282735

mRNA Expression by UniProt/SwissProt for NR1H4 Gene:

Q96RI1-NR1H4_HUMAN
Tissue specificity: Liver and hepatocyte-related cells express mainly FXRalpha1-type isoforms with isoform 3 and isoform 4 in approximately equal proportions. In intestine and kidney mainly FXRalpha2-type isoforms are expressed with isoform 1 and isoform 2 in approximately equal proportions. Expressed in pancreatic beta cells and macrophages.

Evidence on tissue expression from TISSUES for NR1H4 Gene

  • Intestine(4.6)
  • Liver(3.8)
  • Kidney(2.6)
  • Gall bladder(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for NR1H4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • integumentary
  • nervous
  • reproductive
Regions:
Head and neck:
  • eye
  • head
  • mouth
Abdomen:
  • abdominal wall
  • biliary tract
  • gallbladder
  • liver
  • pancreas
General:
  • skin
genes like me logo Genes that share expression patterns with NR1H4: view

Orthologs for NR1H4 Gene

This gene was present in the common ancestor of animals.

Orthologs for NR1H4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NR1H4 31 30
  • 99.59 (n)
OneToOne
cow
(Bos Taurus)
Mammalia NR1H4 31 30
  • 91.36 (n)
OneToOne
dog
(Canis familiaris)
Mammalia NR1H4 31 30
  • 91.04 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Nr1h4 17 31 30
  • 86.21 (n)
rat
(Rattus norvegicus)
Mammalia Nr1h4 30
  • 85.8 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia NR1H4 31
  • 85 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NR1H4 31
  • 83 (a)
OneToOne
chicken
(Gallus gallus)
Aves FXR 31
  • 78 (a)
OneToOne
NR1H4 30
  • 77.9 (n)
lizard
(Anolis carolinensis)
Reptilia NR1H4 31
  • 70 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nr1h4 30
  • 70.34 (n)
African clawed frog
(Xenopus laevis)
Amphibia MGC68693 30
zebrafish
(Danio rerio)
Actinopterygii nr1h4 31 30
  • 65.94 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta EcR 31 32
  • 18 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 38 (a)
OneToOne
Cin.8564 30
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.8564 30
Species where no ortholog for NR1H4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for NR1H4 Gene

ENSEMBL:
Gene Tree for NR1H4 (if available)
TreeFam:
Gene Tree for NR1H4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NR1H4: view image

Paralogs for NR1H4 Gene

(11) SIMAP similar genes for NR1H4 Gene using alignment to 8 proteins:

  • NR1H4_HUMAN
  • B6ZGS9_HUMAN
  • F1DAL1_HUMAN
  • F8W1M1_HUMAN
  • F8W656_HUMAN
  • G8JLB0_HUMAN
  • H0YHD5_HUMAN
  • Q6IPQ7_HUMAN

Pseudogenes.org Pseudogenes for NR1H4 Gene

genes like me logo Genes that share paralogs with NR1H4: view

Variants for NR1H4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NR1H4 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
711574 Benign: not provided 100,510,780(+) G/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
778646 Benign: not provided 100,536,618(+) T/A INTRON_VARIANT
804467 Likely Pathogenic: Cholestasis, progressive familial intrahepatic, 5 100,540,772(+) TC/T FRAMESHIFT_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
rs11110413 Benign: not specified 100,536,932(+) T/A INTRON_VARIANT
rs113090017 Pathogenic: Cholestasis, progressive familial intrahepatic, 5; Cholestasis, progressive familial intrahepatic 1 100,532,538(+) C/T NONSENSE,NON_CODING_TRANSCRIPT_VARIANT,INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for NR1H4 Gene

Structural Variations from Database of Genomic Variants (DGV) for NR1H4 Gene

Variant ID Type Subtype PubMed ID
dgv2832n54 CNV loss 21841781
dgv2833n54 CNV loss 21841781
dgv509e212 CNV loss 25503493
esv2673448 CNV deletion 23128226
esv3549679 CNV deletion 23714750
esv3630555 CNV loss 21293372
nsv1125556 CNV tandem duplication 24896259
nsv1127286 CNV deletion 24896259
nsv442285 CNV loss 18776908
nsv455700 CNV loss 19166990
nsv474397 CNV novel sequence insertion 20440878
nsv559964 CNV gain 21841781
nsv559995 CNV loss 21841781
nsv559996 CNV loss 21841781
nsv560003 CNV loss 21841781

Variation tolerance for NR1H4 Gene

Residual Variation Intolerance Score: 58.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.73; 32.85% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NR1H4 Gene

Human Gene Mutation Database (HGMD)
NR1H4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NR1H4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NR1H4 Gene

Disorders for NR1H4 Gene

MalaCards: The human disease database

(50) MalaCards diseases for NR1H4 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search NR1H4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

NR1H4_HUMAN
  • Note=May be involved in intrahepatic cholestasis of pregnancy. {ECO:0000305 PubMed:17681172}.
  • Note=May be involved in cholesterol cholelithiasis. {ECO:0000305 PubMed:17931734}.
  • Cholestasis, progressive familial intrahepatic, 5 (PFIC5) [MIM:617049]: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC5 is an autosomal recessive, severe form characterized by onset of intralobular cholestasis in the neonatal period. {ECO:0000269 PubMed:26888176}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for NR1H4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with NR1H4: view

No data available for Genatlas for NR1H4 Gene

Publications for NR1H4 Gene

  1. Functional variants of the central bile acid sensor FXR identified in intrahepatic cholestasis of pregnancy. (PMID: 17681172) Van Mil SW … Williamson C (Gastroenterology 2007) 3 4 23 41 54
  2. Ku proteins function as corepressors to regulate farnesoid X receptor-mediated gene expression. (PMID: 19833092) Ohno M … Imagawa M (Biochemical and biophysical research communications 2009) 3 4 23 54
  3. The bile acid receptor FXR is a modulator of intestinal innate immunity. (PMID: 19864602) Vavassori P … Fiorucci S (Journal of immunology (Baltimore, Md. : 1950) 2009) 3 4 23 54
  4. Reciprocal regulation of the bile acid-activated receptor FXR and the interferon-gamma-STAT-1 pathway in macrophages. (PMID: 19393742) Renga B … Fiorucci S (Biochimica et biophysica acta 2009) 3 4 23 54
  5. Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064. (PMID: 19410460) Bass JY … Wisely GB (Bioorganic & medicinal chemistry letters 2009) 3 4 23 54

Products for NR1H4 Gene

Sources for NR1H4 Gene