Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

NR1H4 (nuclear receptor subfamily 1, group H, member 4)

Written2013-12Oscar Briz, Elisa Herraez, Jose JG Marin
Laboratory of Experimental Hepatology, Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain, National Institute of Health, Carlos III, Center for the Study of Liver, Gastrointestinal Diseases (CIBERehd), Madrid, Spain (OB, EH, JJGM); Department of Physiology, Pharmacology, University of Salamanca, Campus Miguel de Unamuno E.D. S-09, 37007 - Salamanca, Spain (JJGM)

(Note : for Links provided by Atlas : click)

Identity

Alias_namesnuclear receptor subfamily 1
Alias_symbol (synonym)FXR
RIP14
HRR1
HRR-1
HGNC (Hugo) NR1H4
LocusID (NCBI) 9971
Atlas_Id 46032
Location 12q23.1  [Link to chromosome band 12q23]
Location_base_pair Starts at 100867551 and ends at 100957645 bp from pter ( according to hg19-Feb_2009)  [Mapping NR1H4.png]

DNA/RNA

 
  A. NR1H4 gene structure. Schematic representation of the NR1H4 gene into 11 exons showing the alternative splicing and the start triplets that generate the 4 known isoforms. These have been classified according to the difference in the initial region of mRNA (α1 and α2) and the presence (+) or absence (-) of a 12-bp insert in the exon 5. B. NCBI reference sequences for FXR variants and isoforms. Variants 1 and 6, and variants 2 and 5 encode the same isoforms.
Description In humans, FXR is encoded by the NR1H4 gene, consisted of 11 exons and 10 introns.
Transcription 4 alternatively spliced transcript variants encoding different isoforms have been described for this gene.
Variants 3 and 4 contain an alternate 5'-terminal exon resulting in isoforms FXRα2 longer than FXRα1, coding by variants 2 and 5, with a distinct N-terminus due to translation initiation from an alternate in-frame start codon in the exon 3. Use of an alternate in-frame donor splice site at exon 5 results in FXRα1(-) and FXRα2(-) variants that miss a 4 amino acid segment compared to FXRα1(+) and FXRα2(+) isoforms.
Pseudogene A pseudogene of FXR has been located on chromosome 1 (1p13.1-1p13.3) (Pseudogene.org).

Protein

Note FXR is a ligand-activated transcription factor belonging to the nuclear receptor superfamily.
 
  FXR isoforms. Schematic representation of FXR isoforms classified based on the presence of the exons 1 and 2 (FXRα1) or 3 (FXRα2) in the initial region of the mRNA and the presence (+) or the absence (-) of the amino acid sequence MYTG in exon 5. AF1 and AF2: ligand-independent and -dependent transactivation domains, respectively; DBD: DNA binding domain; H: hinge region; LBD: ligand binding domain.
Description FXR shares the typical structure of other nuclear receptors, including the N-terminal DNA binding domain (DBD) and the C-terminal ligand binding domain (LBD) (Modica et al., 2010). DBD contains two zinc fingers motifs involved in DNA binding and dimerization with RXRα. Hinge region connects the DBD with the LBD, and contains the insert of the amino acid sequence MYTG in the FXRα1/2(+) isoforms. Ligand-independent (AF-1) and -dependent (AF-2) transactivation domains involved in the interaction with co-repressors and co-activators are located in N- and C-termini, respectively.
Expression FXR is expressed at high levels in the liver, small intestine, kidney and adrenal gland (Huber et al., 2002). Lower FXR levels can be detected in other organs forming the gastrointestinal tract, pancreas, breast and endothelial cells. The liver predominantly expresses FXRα1(+/-), whereas FXRα2(+/-) are the most abundant isoforms in kidney and intestine. In all cases, the proportion of FXRα(1/2)(+) and FXRα(1/2)(-) isoforms is approximately 50% (Vaquero et al., 2013b).
Localisation When activated FXR translocates to the nucleus.
Function Binding of bile acids, the natural ligands of FXR, to the receptor leads its translocation to the cell nucleus, formation of a heterodimer RXRα and binding to FXR response elements on DNA, which activates the transcription of its target genes. Among FXR target genes are those encoding most of the proteins involved in bile acid metabolism and transport (Modica et al., 2010). Additional target genes have recently been described to be involved in FXR-mediated regulation of several body functions, such as prevention of hepatic and intestinal carcinogenesis, liver regeneration, intestinal barrier, attenuation of adverse effects of cholestasis, prevention of gallstone formation, and chemoprotection (Vaquero et al., 2013a). Some of the effects of FXR are mediated by the induction of the small heterodimer partner (SHP), a negative regulator encoded by the NR0B2 gene. This transcription factor interacts with other nuclear receptors blocking its activation. Glucocorticoids are able to directly activate FXR but they also antagonize the expression of FXR and its target genes (Rosales et al., 2013).
Homology DBD domain is a highly conserved domain, whereas LBD domain is moderately conserved in sequence and highly conserved in structure between the various nuclear receptors (Modica et al., 2010). According to sequence homology NR1H4 has been included into the liver-X-receptor-like group of genes belonging to the thyroid hormone receptor-like subfamily of nuclear receptors, together with NR1H2 (liver X receptor-β) and NR1H3 (liver X receptor-α).

Mutations

Note The presence of missense mutations in the NR1H4 gene is unusual, suggesting an important role of this gene in the maintenance of organ function and cellular homeostasis.
 
  Definition, nomenclature, and allelic frequency of clinically relevant NR1H4 genetic variants. MAF refers to the frequency at which the less common allele occurs in a given population according to the NCBI SNP database. Nucleotide positions refer to the ORF of the NM_005123 sequence. Amino acid positions refer to the NP_005114 (FXRα1(-)) or NP_001193921 (FXRα2(-)) proteins. AF-1, ligand-independent transactivation domain.
Somatic c.-1G>T is a common variation resulting in reduced translation efficiency (Marzolini et al., 2007) that might predispose to inflammatory bowel diseases (Attinkara et al., 2012) and intrahepatic cholestasis of pregnancy (Van Mil et al., 2007). c.-189-1174G>A and c.-190+7064C>T are intronic SNP that have been associated with an altered glucose and lipid metabolism (Heni et al., 2013). c.1A>G and c.518T>C are two rare mutations in the coding sequence of FXR whose consequence is a reduction of the function of the protein. Both predispose to intrahepatic cholestasis of pregnancy (Van Mil et al., 2007).

Implicated in

Note
Entity Hepatocellular carcinoma and cholangiocarcinoma
Note FXR is reduced in liver cancer suggesting that FXR is rather working as a tumour suppressor. Knockout mice for FXR spontaneously developed liver tumours after several months. A potential contribution of FXR in tumour suppression can be attributed to its anti-fibrogenic properties in liver. It has also been proposed a role of FXR in prevention of hepatocarcinogenesis by inhibiting the expression of gankyrin (PSMD10), which is activated in liver cancer and modifies the expression of tumour suppressor genes, including Rb, p53, C/EBPα, HNF4α, and p16.
  
Entity Colon cancer
Note Emerging evidences support an important role for FXR in intestinal carcinogenesis. FXR mRNA expression is decreased in colonic polyps, and even more pronounced in colonic adenocarcinoma. Even before carcinomas have formed, FXR loss led to extensive mucosal infiltration of neutrophils and macrophages along with increased TNF-α mRNA expression and nuclear β-catenin accumulation. FXR deficiency led to increased susceptibility to tumour development by promoting WTN-β-catenin signalling through TNF-α released by infiltrated macrophages. In contrast to this indirect oncosupressive role of FXR, by maintaining intestinal epithelium integrity, FXR also carries out a direct oncosupressor activity. Thereby, several data suggest that FXR activation enhances apoptosis and inhibits cell proliferation by increasing the expression of proapoptotic genes including p21, BAK1, FADD, and repressing antiapoptotic genes, such as BCL-2.
  
Entity Chemoresistance
Note Ligand-dependent and independent activation of FXR and/or its signalling pathway is involved in the chemoprotective response of liver cells. This is due in part to changes in the expression of several genes (ABCB4, TCEA2, CCL14, CCL15 and KRT13) accounting for different MOC, mainly these involved in drug efflux (MOC-1b), DNA repair (MOC-4) and cell survival (MOC-5b). Moreover, this characteristic is shared by healthy and tumour cells, and hence may play an important role in enhancing the chemoprotection of healthy hepatocytes against genotoxic compounds and reducing the response of liver tumour cells to certain pharmacological treatments.
Disease The development of chemoresistance depends on the expression of the genes involved in a variety of mechanisms of chemoresistance (MOC), which are present in both healthy tissues, where they are involved in the defence against the chemical stress caused by potentially toxic compounds, and in cancer cells, where they account for the poor response to antitumour drugs.
  
Entity Cholestasis
Note FXR has a crucial role in maintaining bile acid homeostasis, especially during cholestasis. Upon activation by enhanced bile acid levels FXR mediates responses that partially protect the hepatocyte from the deleterious effect of accumulation of toxic bile acids. FXR inhibits bile acid synthesis in liver, through down-regulation of key enzymes in bile acid biosynthesis, such as CYP7A1 and CYP8B1. It also diminishes bile acid uptake by hepatocytes by repressing the expression of Na+-taurocholate cotransporting polypeptide or NTCP (gene symbol SLC10A1), and increases bile acid efflux by inducing the expression of ABC proteins at the canalicular membrane, such as including BSEP (ABCB11) and MDR3 (ABCB4) involved in bile acid-dependent phospholipid secretion. FXR up-regulates the phase II enzymes uridine 5'-diphosphate-glucuronosyltransferase 2B4 (UGT2B4) and sulphotransferase 2A1 (SULT2A1), which glucuronidate or sulphate bile acids to render them more hydrophilic, less biologically active, and more easily to be eliminated from the body. In the intestine FXR-induced reduction of bile acid uptake by enterocytes due to transcriptional repression of ASBT (SLC10A2), which enhances bile acid faecal loss. Moreover, FXR increases the transcription of FGF19 in the ileum, triggering a signalling pathway that represses hepatic CYP7A1 expression, and hence down-regulation of bile acid synthesis.
Disease Cholestasis, which is characterized by the accumulation of bile acids in liver and is associated with reduced detoxification capacity.
  
Entity Cirrhosis
Note FXR is expressed in hepatic stellate cells, and its activation reduces the expression of extracellular matrix proteins by these cells, preventing liver fibrosis.
Disease Cirrhosis is a result of advanced liver disease that is characterized by replacement of liver tissue by fibrosis and regenerative nodules, leading loss of liver function.
  
Entity Cholelithiasis
Note FXR prevents gallstone formation by up-regulation of ABC proteins accounting for canalicular secretion of bile acids (BSEP) and phospholipids (MDR3), resulting in enhanced mixed micelle formation capability and, hence prevention of cholesterol crystallization in bile.
Disease Cholelithiasis is a pathological situation characterized by presence in the gallbladder, of stones, a crystalline concretion formed by accretion of bile components.
  
Entity Hepatic regeneration
Note FXR participates in bile acid-induced liver repair by promoting regeneration through regulation of the FoxM1b expression, a Forkhead Box transcription factor, which regulates cell cycle progression during liver regeneration. Moreover, FXR helps restoration of organ homeostasis.
Disease Liver regeneration after loss of hepatic tissue is an adaptive response to repair injury consisting of induction of proliferative factors that activate the quiescent hepatocytes, followed by re-establishment of normal liver size and renewed hepatocyte quiescence.
  
Entity Intestinal diseases
Note FXR plays an important role in the protection against bacterial overgrowth and the maintenance of intestinal barrier function, and it has recently been involved in the pathogenesis of idiopathic inflammatory bowel disease. FXR activation in the intestinal tract decreases the production of proinflammatory cytokines such as IL1-β, IL-2, IL-6, tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), thus contributing to a reduction of inflammation and epithelial permeability. In addition, intestinal FXR activation induces the expression of genes with antibacterial properties involved in enteroprotection and prevention of bacterial translocation in the intestinal tract, including angiogenin, carbonic anhydrase 12 or inducible nitric oxide synthase.
Disease Intestinal bacterial proliferation and translocation, chronic diarrhoea and inflammatory bowel disease.
  

Breakpoints

Note NR1H4 gene is not involved in breakpoint regions.

Bibliography

Association of genetic variation in the NR1H4 gene, encoding the nuclear bile acid receptor FXR, with inflammatory bowel disease.
Attinkara R, Mwinyi J, Truninger K, Regula J, Gaj P, Rogler G, Kullak-Ublick GA, Eloranta JJ; Swiss IBD Cohort Study Group.
BMC Res Notes. 2012 Aug 28;5:461. doi: 10.1186/1756-0500-5-461.
PMID 22929053
 
Genetic variation in NR1H4 encoding the bile acid receptor FXR determines fasting glucose and free fatty acid levels in humans.
Heni M, Wagner R, Ketterer C, Bohm A, Linder K, Machicao F, Machann J, Schick F, Hennige AM, Stefan N, Haring HU, Fritsche A, Staiger H.
J Clin Endocrinol Metab. 2013 Jul;98(7):E1224-9. doi: 10.1210/jc.2013-1177. Epub 2013 May 2.
PMID 23640969
 
Generation of multiple farnesoid-X-receptor isoforms through the use of alternative promoters.
Huber RM, Murphy K, Miao B, Link JR, Cunningham MR, Rupar MJ, Gunyuzlu PL, Haws TF, Kassam A, Powell F, Hollis GF, Young PR, Mukherjee R, Burn TC.
Gene. 2002 May 15;290(1-2):35-43.
PMID 12062799
 
A common polymorphism in the bile acid receptor farnesoid X receptor is associated with decreased hepatic target gene expression.
Marzolini C, Tirona RG, Gervasini G, Poonkuzhali B, Assem M, Lee W, Leake BF, Schuetz JD, Schuetz EG, Kim RB.
Mol Endocrinol. 2007 Aug;21(8):1769-80. Epub 2007 May 22.
PMID 17519356
 
Deciphering the nuclear bile acid receptor FXR paradigm.
Modica S, Gadaleta RM, Moschetta A.
Nucl Recept Signal. 2010 Nov 19;8:e005. doi: 10.1621/nrs.08005. (REVIEW)
PMID 21383957
 
FXR-dependent and -independent interaction of glucocorticoids with the regulatory pathways involved in the control of bile acid handling by the liver.
Rosales R, Romero MR, Vaquero J, Monte MJ, Requena P, Martinez-Augustin O, Sanchez de Medina F, Marin JJ.
Biochem Pharmacol. 2013 Mar 15;85(6):829-38. doi: 10.1016/j.bcp.2013.01.001. Epub 2013 Jan 10.
PMID 23313557
 
Functional variants of the central bile acid sensor FXR identified in intrahepatic cholestasis of pregnancy.
Van Mil SW, Milona A, Dixon PH, Mullenbach R, Geenes VL, Chambers J, Shevchuk V, Moore GE, Lammert F, Glantz AG, Mattsson LA, Whittaker J, Parker MG, White R, Williamson C.
Gastroenterology. 2007 Aug;133(2):507-16. Epub 2007 May 23.
PMID 17681172
 
Activation of the nuclear receptor FXR enhances hepatocyte chemoprotection and liver tumor chemoresistance against genotoxic compounds.
Vaquero J, Briz O, Herraez E, Muntane J, Marin JJ.
Biochim Biophys Acta. 2013a Oct;1833(10):2212-9. doi: 10.1016/j.bbamcr.2013.05.006. Epub 2013 May 13.
PMID 23680185
 
Differential activation of the human farnesoid X receptor depends on the pattern of expressed isoforms and the bile acid pool composition.
Vaquero J, Monte MJ, Dominguez M, Muntane J, Marin JJ.
Biochem Pharmacol. 2013b Oct 1;86(7):926-39. doi: 10.1016/j.bcp.2013.07.022. Epub 2013 Aug 6.
PMID 23928191
 

Citation

This paper should be referenced as such :
Briz, O ; Herraez, E ; Marin, JJG
NR1H4 (nuclear receptor subfamily 1, group H, member 4)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(8):571-575.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/NR1H4ID46032ch12q23.html


External links

Nomenclature
HGNC (Hugo)NR1H4   7967
Cards
AtlasNR1H4ID46032ch12q23
Entrez_Gene (NCBI)NR1H4  9971  nuclear receptor subfamily 1 group H member 4
AliasesBAR; FXR; HRR-1; HRR1; 
PFIC5; RIP14
GeneCards (Weizmann)NR1H4
Ensembl hg19 (Hinxton)ENSG00000012504 [Gene_View]  chr12:100867551-100957645 [Contig_View]  NR1H4 [Vega]
Ensembl hg38 (Hinxton)ENSG00000012504 [Gene_View]  chr12:100867551-100957645 [Contig_View]  NR1H4 [Vega]
ICGC DataPortalENSG00000012504
TCGA cBioPortalNR1H4
AceView (NCBI)NR1H4
Genatlas (Paris)NR1H4
WikiGenes9971
SOURCE (Princeton)NR1H4
Genetics Home Reference (NIH)NR1H4
Genomic and cartography
GoldenPath hg19 (UCSC)NR1H4  -     chr12:100867551-100957645 +  12q23.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)NR1H4  -     12q23.1   [Description]    (hg38-Dec_2013)
EnsemblNR1H4 - 12q23.1 [CytoView hg19]  NR1H4 - 12q23.1 [CytoView hg38]
Mapping of homologs : NCBINR1H4 [Mapview hg19]  NR1H4 [Mapview hg38]
OMIM603826   617049   
Gene and transcription
Genbank (Entrez)AB307699 AF384555 AF478445 AF478446 AK296612
RefSeq transcript (Entrez)NM_001206977 NM_001206978 NM_001206979 NM_001206992 NM_001206993 NM_005123
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)NR1H4
Cluster EST : UnigeneHs.732506 [ NCBI ]
CGAP (NCI)Hs.732506
Alternative Splicing GalleryENSG00000012504
Gene ExpressionNR1H4 [ NCBI-GEO ]   NR1H4 [ EBI - ARRAY_EXPRESS ]   NR1H4 [ SEEK ]   NR1H4 [ MEM ]
Gene Expression Viewer (FireBrowse)NR1H4 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9971
GTEX Portal (Tissue expression)NR1H4
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ96RI1   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ96RI1  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ96RI1
Splice isoforms : SwissVarQ96RI1
PhosPhoSitePlusQ96RI1
Domaine pattern : Prosite (Expaxy)NUCLEAR_REC_DBD_1 (PS00031)    NUCLEAR_REC_DBD_2 (PS51030)   
Domains : Interpro (EBI)Nucl_hrmn_rcpt_lig-bd    Nuclear_hrmn_rcpt    ThyrH_rcpt    Znf_hrmn_rcpt    Znf_NHR/GATA   
Domain families : Pfam (Sanger)Hormone_recep (PF00104)    zf-C4 (PF00105)   
Domain families : Pfam (NCBI)pfam00104    pfam00105   
Domain families : Smart (EMBL)HOLI (SM00430)  ZnF_C4 (SM00399)  
Conserved Domain (NCBI)NR1H4
DMDM Disease mutations9971
Blocks (Seattle)NR1H4
PDB (SRS)1OSH    1OSK    3BEJ    3DCT    3DCU    3FLI    3FXV    3GD2    3HC5    3HC6    3L1B    3OKH    3OKI    3OLF    3OMK    3OMM    3OOF    3OOK    3P88    3P89    3RUT    3RUU    3RVF    4OIV    4QE6    4QE8    4WVD   
PDB (PDBSum)1OSH    1OSK    3BEJ    3DCT    3DCU    3FLI    3FXV    3GD2    3HC5    3HC6    3L1B    3OKH    3OKI    3OLF    3OMK    3OMM    3OOF    3OOK    3P88    3P89    3RUT    3RUU    3RVF    4OIV    4QE6    4QE8    4WVD   
PDB (IMB)1OSH    1OSK    3BEJ    3DCT    3DCU    3FLI    3FXV    3GD2    3HC5    3HC6    3L1B    3OKH    3OKI    3OLF    3OMK    3OMM    3OOF    3OOK    3P88    3P89    3RUT    3RUU    3RVF    4OIV    4QE6    4QE8    4WVD   
PDB (RSDB)1OSH    1OSK    3BEJ    3DCT    3DCU    3FLI    3FXV    3GD2    3HC5    3HC6    3L1B    3OKH    3OKI    3OLF    3OMK    3OMM    3OOF    3OOK    3P88    3P89    3RUT    3RUU    3RVF    4OIV    4QE6    4QE8    4WVD   
Structural Biology KnowledgeBase1OSH    1OSK    3BEJ    3DCT    3DCU    3FLI    3FXV    3GD2    3HC5    3HC6    3L1B    3OKH    3OKI    3OLF    3OMK    3OMM    3OOF    3OOK    3P88    3P89    3RUT    3RUU    3RVF    4OIV    4QE6    4QE8    4WVD   
SCOP (Structural Classification of Proteins)1OSH    1OSK    3BEJ    3DCT    3DCU    3FLI    3FXV    3GD2    3HC5    3HC6    3L1B    3OKH    3OKI    3OLF    3OMK    3OMM    3OOF    3OOK    3P88    3P89    3RUT    3RUU    3RVF    4OIV    4QE6    4QE8    4WVD   
CATH (Classification of proteins structures)1OSH    1OSK    3BEJ    3DCT    3DCU    3FLI    3FXV    3GD2    3HC5    3HC6    3L1B    3OKH    3OKI    3OLF    3OMK    3OMM    3OOF    3OOK    3P88    3P89    3RUT    3RUU    3RVF    4OIV    4QE6    4QE8    4WVD   
SuperfamilyQ96RI1
Human Protein AtlasENSG00000012504
Peptide AtlasQ96RI1
HPRD04827
IPIIPI00045302   IPI00220798   IPI00168867   IPI00410346   IPI01020869   IPI01021708   IPI01023023   IPI01022884   IPI01022446   
Protein Interaction databases
DIP (DOE-UCLA)Q96RI1
IntAct (EBI)Q96RI1
FunCoupENSG00000012504
BioGRIDNR1H4
STRING (EMBL)NR1H4
ZODIACNR1H4
Ontologies - Pathways
QuickGOQ96RI1
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II distal enhancer sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  nitrogen catabolite activation of transcription from RNA polymerase II promoter  transcriptional activator activity, RNA polymerase II transcription factor binding  transcription factor activity, sequence-specific DNA binding  transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding  steroid hormone receptor activity  transcription coactivator activity  transcription corepressor activity  RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding  RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding  thyroid hormone receptor activity  protein binding  nucleoplasm  nuclear euchromatin  transcription initiation from RNA polymerase II promoter  inflammatory response  cell-cell junction assembly  signal transduction  Notch signaling pathway  bile acid metabolic process  zinc ion binding  negative regulation of tumor necrosis factor-mediated signaling pathway  regulation of low-density lipoprotein particle clearance  bile acid and bile salt transport  ligand-dependent nuclear receptor binding  intracellular receptor signaling pathway  bile acid binding  bile acid binding  negative regulation of NF-kappaB transcription factor activity  negative regulation of interleukin-1 production  negative regulation of interleukin-2 production  negative regulation of interleukin-6 production  toll-like receptor 4 signaling pathway  toll-like receptor 9 signaling pathway  regulation of urea metabolic process  histone H3-R17 methylation  cellular triglyceride homeostasis  positive regulation of insulin secretion involved in cellular response to glucose stimulus  bile acid receptor activity  bile acid receptor activity  bile acid signaling pathway  bile acid signaling pathway  intracellular bile acid receptor signaling pathway  glucose homeostasis  defense response to bacterium  negative regulation of apoptotic process  negative regulation of I-kappaB kinase/NF-kappaB signaling  steroid hormone mediated signaling pathway  sequence-specific DNA binding  innate immune response  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of insulin receptor signaling pathway  retinoid X receptor binding  negative regulation of inflammatory response  fatty acid homeostasis  regulation of insulin secretion involved in cellular response to glucose stimulus  regulation of bile acid biosynthetic process  negative regulation of bile acid biosynthetic process  cellular response to lipopolysaccharide  cellular response to fatty acid  cellular response to organonitrogen compound  negative regulation of monocyte chemotactic protein-1 production  interleukin-17 secretion  regulation of cholesterol metabolic process  chenodeoxycholic acid binding  negative regulation of interferon-gamma secretion  positive regulation of adipose tissue development  negative regulation of tumor necrosis factor secretion  positive regulation of phosphatidic acid biosynthetic process  regulation of cholesterol homeostasis  positive regulation of glutamate metabolic process  positive regulation of ammonia assimilation cycle  positive regulation of glucose import in response to insulin stimulus  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II distal enhancer sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  nitrogen catabolite activation of transcription from RNA polymerase II promoter  transcriptional activator activity, RNA polymerase II transcription factor binding  transcription factor activity, sequence-specific DNA binding  transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding  steroid hormone receptor activity  transcription coactivator activity  transcription corepressor activity  RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding  RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding  thyroid hormone receptor activity  protein binding  nucleoplasm  nuclear euchromatin  transcription initiation from RNA polymerase II promoter  inflammatory response  cell-cell junction assembly  signal transduction  Notch signaling pathway  bile acid metabolic process  zinc ion binding  negative regulation of tumor necrosis factor-mediated signaling pathway  regulation of low-density lipoprotein particle clearance  bile acid and bile salt transport  ligand-dependent nuclear receptor binding  intracellular receptor signaling pathway  bile acid binding  bile acid binding  negative regulation of NF-kappaB transcription factor activity  negative regulation of interleukin-1 production  negative regulation of interleukin-2 production  negative regulation of interleukin-6 production  toll-like receptor 4 signaling pathway  toll-like receptor 9 signaling pathway  regulation of urea metabolic process  histone H3-R17 methylation  cellular triglyceride homeostasis  positive regulation of insulin secretion involved in cellular response to glucose stimulus  bile acid receptor activity  bile acid receptor activity  bile acid signaling pathway  bile acid signaling pathway  intracellular bile acid receptor signaling pathway  glucose homeostasis  defense response to bacterium  negative regulation of apoptotic process  negative regulation of I-kappaB kinase/NF-kappaB signaling  steroid hormone mediated signaling pathway  sequence-specific DNA binding  innate immune response  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of insulin receptor signaling pathway  retinoid X receptor binding  negative regulation of inflammatory response  fatty acid homeostasis  regulation of insulin secretion involved in cellular response to glucose stimulus  regulation of bile acid biosynthetic process  negative regulation of bile acid biosynthetic process  cellular response to lipopolysaccharide  cellular response to fatty acid  cellular response to organonitrogen compound  negative regulation of monocyte chemotactic protein-1 production  interleukin-17 secretion  regulation of cholesterol metabolic process  chenodeoxycholic acid binding  negative regulation of interferon-gamma secretion  positive regulation of adipose tissue development  negative regulation of tumor necrosis factor secretion  positive regulation of phosphatidic acid biosynthetic process  regulation of cholesterol homeostasis  positive regulation of glutamate metabolic process  positive regulation of ammonia assimilation cycle  positive regulation of glucose import in response to insulin stimulus  
Pathways : BIOCARTAFXR and LXR Regulation of Cholesterol Metabolism [Genes]    Nuclear Receptors in Lipid Metabolism and Toxicity [Genes]   
Pathways : KEGGBile secretion   
REACTOMEQ96RI1 [protein]
REACTOME PathwaysR-HSA-211976 [pathway]
NDEx NetworkNR1H4
Atlas of Cancer Signalling NetworkNR1H4
Wikipedia pathwaysNR1H4
Orthology - Evolution
OrthoDB9971
GeneTree (enSembl)ENSG00000012504
Phylogenetic Trees/Animal Genes : TreeFamNR1H4
HOVERGENQ96RI1
HOGENOMQ96RI1
Homologs : HomoloGeneNR1H4
Homology/Alignments : Family Browser (UCSC)NR1H4
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerNR1H4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)NR1H4
dbVarNR1H4
ClinVarNR1H4
1000_GenomesNR1H4 
Exome Variant ServerNR1H4
ExAC (Exome Aggregation Consortium)NR1H4 (select the gene name)
Genetic variants : HAPMAP9971
Genomic Variants (DGV)NR1H4 [DGVbeta]
DECIPHER (Syndromes)12:100867551-100957645  ENSG00000012504
CONAN: Copy Number AnalysisNR1H4 
Mutations
ICGC Data PortalNR1H4 
TCGA Data PortalNR1H4 
Broad Tumor PortalNR1H4
OASIS PortalNR1H4 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICNR1H4  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDNR1H4
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch NR1H4
DgiDB (Drug Gene Interaction Database)NR1H4
DoCM (Curated mutations)NR1H4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)NR1H4 (select a term)
intoGenNR1H4
NCG5 (London)NR1H4
Cancer3DNR1H4(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603826    617049   
Orphanet10933   
MedgenNR1H4
Genetic Testing Registry NR1H4
NextProtQ96RI1 [Medical]
TSGene9971
GENETestsNR1H4
Huge Navigator NR1H4 [HugePedia]
snp3D : Map Gene to Disease9971
BioCentury BCIQNR1H4
ClinGenNR1H4
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9971
Chemical/Pharm GKB GenePA31752
Clinical trialNR1H4
Miscellaneous
canSAR (ICR)NR1H4 (select the gene name)
Probes
Litterature
PubMed221 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineNR1H4
EVEXNR1H4
GoPubMedNR1H4
iHOPNR1H4
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Jan 21 16:42:12 CET 2017

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.