NR1H4 report

I. Expression across cell types

II. Expression across tissues

sc-RNAseq data

Insufficient scRNA-seq data for expression of NR1H4 at tissue level.

III. Associated gene sets

GO_0071417Biological processcellular response to organonitrogen compound
GO_0090181Biological processregulation of cholesterol metabolic process
GO_0010903Biological processnegative regulation of very-low-density lipoprotein particle remodeling
GO_1904179Biological processpositive regulation of adipose tissue development
GO_0006366Biological processtranscription by RNA polymerase II
GO_0007043Biological processcell-cell junction assembly
GO_0006954Biological processinflammatory response
GO_0055089Biological processfatty acid homeostasis
GO_0008206Biological processbile acid metabolic process
GO_0007219Biological processNotch signaling pathway
GO_0032692Biological processnegative regulation of interleukin-1 production
GO_0032703Biological processnegative regulation of interleukin-2 production
GO_0032715Biological processnegative regulation of interleukin-6 production
GO_0045087Biological processinnate immune response
GO_0006357Biological processregulation of transcription by RNA polymerase II
GO_0038185Biological processnuclear receptor-mediated bile acid signaling pathway
GO_0071638Biological processnegative regulation of monocyte chemotactic protein-1 production
GO_1903413Biological processcellular response to bile acid
GO_0030522Biological processintracellular receptor signaling pathway
GO_2000213Biological processpositive regulation of glutamate metabolic process
GO_0000122Biological processnegative regulation of transcription by RNA polymerase II
GO_0001678Biological processintracellular glucose homeostasis
GO_2001250Biological processpositive regulation of ammonia assimilation cycle
GO_0010988Biological processregulation of low-density lipoprotein particle clearance
GO_0042632Biological processcholesterol homeostasis
GO_0035774Biological processpositive regulation of insulin secretion involved in cellular response to glucose stimulus
GO_0038183Biological processbile acid signaling pathway
GO_0050728Biological processnegative regulation of inflammatory response
GO_0043066Biological processnegative regulation of apoptotic process
GO_0045893Biological processpositive regulation of DNA-templated transcription
GO_0061178Biological processregulation of insulin secretion involved in cellular response to glucose stimulus
GO_0030154Biological processcell differentiation
GO_1905695Biological processpositive regulation of phosphatidic acid biosynthetic process
GO_0042742Biological processdefense response to bacterium
GO_0046628Biological processpositive regulation of insulin receptor signaling pathway
GO_0001080Biological processnitrogen catabolite activation of transcription from RNA polymerase II promoter
GO_0071222Biological processcellular response to lipopolysaccharide
GO_0032689Biological processnegative regulation of type II interferon production
GO_0070857Biological processregulation of bile acid biosynthetic process
GO_0032720Biological processnegative regulation of tumor necrosis factor production
GO_0010804Biological processnegative regulation of tumor necrosis factor-mediated signaling pathway
GO_0043124Biological processnegative regulation of canonical NF-kappaB signal transduction
GO_0034255Biological processregulation of urea metabolic process
GO_0032740Biological processpositive regulation of interleukin-17 production
GO_0035356Biological processintracellular triglyceride homeostasis
GO_0034162Biological processtoll-like receptor 9 signaling pathway
GO_0045944Biological processpositive regulation of transcription by RNA polymerase II
GO_0071398Biological processcellular response to fatty acid
GO_0043235Cellular componentreceptor complex
GO_0000791Cellular componenteuchromatin
GO_0005654Cellular componentnucleoplasm
GO_0090575Cellular componentRNA polymerase II transcription regulator complex
GO_0000785Cellular componentchromatin
GO_0005634Cellular componentnucleus
GO_0000978Molecular functionRNA polymerase II cis-regulatory region sequence-specific DNA binding
GO_0016922Molecular functionnuclear receptor binding
GO_0001228Molecular functionDNA-binding transcription activator activity, RNA polymerase II-specific
GO_0000977Molecular functionRNA polymerase II transcription regulatory region sequence-specific DNA binding
GO_0000981Molecular functionDNA-binding transcription factor activity, RNA polymerase II-specific
GO_0043565Molecular functionsequence-specific DNA binding
GO_1902122Molecular functionchenodeoxycholic acid binding
GO_0004879Molecular functionnuclear receptor activity
GO_0001221Molecular functiontranscription coregulator binding
GO_0032052Molecular functionbile acid binding
GO_0046965Molecular functionnuclear retinoid X receptor binding
GO_0003700Molecular functionDNA-binding transcription factor activity
GO_0008270Molecular functionzinc ion binding
GO_0005515Molecular functionprotein binding

IV. Literature review

[source]
Gene nameNR1H4
Protein nameFarnesoid X nuclear receptor
Nuclear receptor subfamily 1 group H member 4
Bile acid receptor (Farnesoid X-activated receptor) (Farnesol receptor HRR-1) (Nuclear receptor subfamily 1 group H member 4) (Retinoid X receptor-interacting protein 14) (RXR-interacting protein 14)
Farnesoid X receptor (Nuclear receptor subfamily 1, group H, member 4, isoform CRA_a)
NR1H4 protein
SynonymsRIP14
hCG_20893
BAR
HRR1
FXR
DescriptionFUNCTION: 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 . 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) . 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) . In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression . 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 . 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 . Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance) . Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element . Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase) . 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 . 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 . 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 . Involved in the TLR9-mediated protective mechanism in intestinal inflammation. Plays an anti-inflammatory role in liver inflammation; proposed to inhibit pro-inflammatory (but not antiapoptotic) NF-kappa-B signaling) (By similarity). .; 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. .; 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. .; 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. .; 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. .

AccessionsF8W1M1
ENST00000548621.2
ENST00000549996.5 [Q96RI1-5]
ENST00000392986.8 [Q96RI1-1]
ENST00000551379.5 [Q96RI1-3]
B6ZGS9
H0YHD5
ENST00000321046.9
G8JLB0
ENST00000548884.5 [Q96RI1-2]
ENST00000188403.7 [Q96RI1-4]
F1DAL1
ENST00000649582.1
ENST00000551184.1
Q96RI1
F8W656
Q6IPQ7
ENST00000546380.1
ENST00000648861.1 [Q96RI1-1]