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Aliases for NR1H4 Gene

Aliases for NR1H4 Gene

  • Nuclear Receptor Subfamily 1 Group H Member 4 2 3 4 5
  • 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

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 Intrahepatic Cholestasis and Biliary Tract Disease. Among its related pathways are Gene Expression and Bile secretion. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and receptor activity. An important paralog of this gene is NR4A2.

UniProtKB/Swiss-Prot 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 homoestasis 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 a 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

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NR1H4 Gene

Genomics for NR1H4 Gene

Regulatory Elements for NR1H4 Gene

Enhancers for NR1H4 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around NR1H4 on UCSC Golden Path with GeneCards custom track

Promoters for NR1H4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around NR1H4 on UCSC Golden Path with GeneCards custom track

Genomic Location for NR1H4 Gene

Chromosome:
12
Start:
100,473,708 bp from pter
End:
100,564,413 bp from pter
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:
    • 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.
    SequenceCaution:
    • Sequence=BC144183; Type=Frameshift; Positions=156; 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

Proteomics data for NR1H4 Gene at MOPED

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

Antibody Products

No data available for DME Specific Peptides for NR1H4 Gene

Domains & Families for NR1H4 Gene

Gene Families for NR1H4 Gene

Graphical View of Domain Structure for InterPro Entry

Q96RI1

UniProtKB/Swiss-Prot:

NR1H4_HUMAN :
  • Contains 1 nuclear receptor DNA-binding domain.
  • Belongs to the nuclear hormone receptor family. NR1 subfamily.
Domain:
  • Contains 1 nuclear receptor DNA-binding domain.
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 homoestasis 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 a 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.

Gene Ontology (GO) - Molecular Function for NR1H4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding IDA 24211198
GO:0016922 ligand-dependent nuclear receptor binding TAS 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

Flow Cytometry 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
Jensen Localization Image for NR1H4 Gene COMPARTMENTS Subcellular localization image for NR1H4 gene
Compartment Confidence
nucleus 5
extracellular 2
peroxisome 2
plasma membrane 2
cytosol 1
endoplasmic reticulum 1
mitochondrion 1

No data available for Gene Ontology (GO) - Cellular Components for NR1H4 Gene

Pathways & Interactions for NR1H4 Gene

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

SIGNOR curated interactions for NR1H4 Gene

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 from RNA polymerase II promoter ISS 21757002
GO:0006109 regulation of carbohydrate metabolic process IEA --
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006367 transcription initiation from RNA polymerase II promoter TAS --
genes like me logo Genes that share ontologies with NR1H4: view

Drugs & Compounds for NR1H4 Gene

(27) 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, Target, other 27
deoxycholic acid Approved Pharma Antagonist 39
Fexaramine Experimental Pharma Agonist, Target Potent, selective farnesoid X receptor (FXR) agonist 0
(8alpha,10alpha,13alpha,17beta)-17-[(4-hydroxyphenyl)carbonyl]androsta-3,5-diene-3-carboxylic acid Experimental Pharma Target 0
GW4064 Pharma Agonist Non-steroidal FXR agonist,potent and selective 0

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
GW 4064
278779-30-9
ECDCA
Agonist
DY 268
1609564-75-1
GW 3965 hydrochloride
405911-17-3

(5) Tocris Compounds for NR1H4 Gene

Compound Action Cas Number
DY 268 Potent FXR antagonist 1609564-75-1
Fexaramine Potent, selective farnesoid X receptor (FXR) agonist 574013-66-4
GW 3965 hydrochloride Orally active liver X receptor (LXR) agonist 405911-17-3
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

(5) ApexBio Compounds for NR1H4 Gene

Compound Action Cas Number
Chenodeoxycholic Acid 474-25-9
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
genes like me logo Genes that share compounds with NR1H4: view

Drug Products

Transcripts for NR1H4 Gene

Unigene Clusters for NR1H4 Gene

Nuclear receptor subfamily 1, group H, member 4:
Representative Sequences:

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
ECgene alternative splicing isoforms for
NR1H4

Expression for NR1H4 Gene

mRNA expression in normal human tissues 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, PaxDb, and MOPED for NR1H4 Gene



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 approximative equal proportions. In intestine and kidney mainly FXRalpha2-type isoforms are expressed with isoform 1 and isoform 2 in approximative equal proportions. Expressed in pancreatic beta cells and macrophages.
genes like me logo Genes that share expression patterns with NR1H4: view

Protein tissue co-expression partners for NR1H4 Gene

Primer Products

Orthologs for NR1H4 Gene

This gene was present in the common ancestor of animals.

Orthologs for NR1H4 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia NR1H4 35
  • 91.36 (n)
  • 93.57 (a)
NR1H4 36
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NR1H4 35
  • 91.04 (n)
  • 94.67 (a)
NR1H4 36
  • 93 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Nr1h4 35
  • 86.21 (n)
  • 92.8 (a)
Nr1h4 16
Nr1h4 36
  • 92 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia NR1H4 35
  • 99.59 (n)
  • 99.79 (a)
NR1H4 36
  • 95 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nr1h4 35
  • 85.8 (n)
  • 93.5 (a)
oppossum
(Monodelphis domestica)
Mammalia NR1H4 36
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NR1H4 36
  • 85 (a)
OneToOne
chicken
(Gallus gallus)
Aves NR1H4 35
  • 77.9 (n)
  • 82.47 (a)
FXR 36
  • 78 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NR1H4 36
  • 70 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nr1h4 35
  • 70.34 (n)
  • 70.42 (a)
African clawed frog
(Xenopus laevis)
Amphibia MGC68693 35
zebrafish
(Danio rerio)
Actinopterygii nr1h4 35
  • 65.94 (n)
  • 67.03 (a)
nr1h4 36
  • 63 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta EcR 37
  • 36 (a)
EcR 36
  • 18 (a)
OneToMany
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.8564 35
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 38 (a)
OneToOne
Species with no ortholog for NR1H4:
  • 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)

Paralogs for NR1H4 Gene

Paralogs for NR1H4 Gene

Pseudogenes.org Pseudogenes for NR1H4 Gene

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

Variants for NR1H4 Gene

Sequence variations from dbSNP and Humsavar for NR1H4 Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type
rs2025801 -- 100,480,292(-) GACAG(A/G)CACTA intron-variant
rs2031706 -- 100,505,882(+) CTAAC(C/G)CTTGA intron-variant
rs2069075 -- 100,521,329(-) TGTCA(C/T)TCTGC intron-variant
rs7133810 -- 100,551,712(+) TTGCT(C/T)GGTTT intron-variant
rs35724 -- 100,561,600(-) CTCTT(C/G)AATTG intron-variant

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

Variant ID Type Subtype PubMed ID
nsv455700 CNV Loss 19166990
dgv1484n71 CNV Gain 21882294
nsv899470 CNV Gain 21882294
esv2673448 CNV Deletion 23128226
nsv442285 CNV CNV 18776908

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)

Relevant External Links for NR1H4 Gene

Human Gene Mutation Database (HGMD)
NR1H4

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

Disorders for NR1H4 Gene

MalaCards: The human disease database

(25) MalaCards diseases for NR1H4 Gene - From: Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
intrahepatic cholestasis
  • intrahepatic cholestasis of pregnancy
biliary tract disease
  • biliary tract diseases
primary biliary cirrhosis
  • biliary liver cirrhosis
cholestasis
  • bile occlusion
cerebrotendinous xanthomatosis
  • cholestanol storage disease
- 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 cholesterol cholelithiasis. {ECO:0000305 PubMed:17931734}.
  • Note=May be involved in intrahepatic cholestasis of pregnancy. {ECO:0000305 PubMed:17681172}.

Relevant External Links for NR1H4

Genetic Association Database (GAD)
NR1H4
Human Genome Epidemiology (HuGE) Navigator
NR1H4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
NR1H4
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 S.W. … Williamson C. (Gastroenterology 2007) 3 4 23 48 67
  2. Identification of a nuclear receptor for bile acids. (PMID: 10334992) Makishima M. … Shan B. (Science 1999) 3 23 25
  3. Structure-activity relationship of bile alcohols as human farnesoid X receptor agonist. (PMID: 19913569) Iguchi Y. … Une M. (Steroids 2010) 3 23
  4. Farnesoid X receptor, through the binding with steroidogenic factor 1-responsive element, inhibits aromatase expression in tumor Leydig cells. (PMID: 20026603) Catalano S. … AndA^ S. (J. Biol. Chem. 2010) 3 23
  5. Regulation of the human bile acid UDP-glucuronosyltransferase 1A3 by the farnesoid X receptor and bile acids. (PMID: 20189675) Erichsen T.J. … Strassburg C.P. (J. Hepatol. 2010) 3 23

Products for NR1H4 Gene

Sources for NR1H4 Gene

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