Farnesoid X receptor

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Nuclear receptor subfamily 1, group H, member 4
Protein NR1H4 PDB 1osh.png
PDB rendering based on 1osh.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols NR1H4 ; BAR; FXR; HRR-1; HRR1; RIP14
External IDs OMIM603826 MGI1352464 HomoloGene3760 IUPHAR: 603 ChEMBL: 2047 GeneCards: NR1H4 Gene
RNA expression pattern
PBB GE NR1H4 206340 at tn.png
More reference expression data
Species Human Mouse
Entrez 9971 20186
Ensembl ENSG00000012504 ENSMUSG00000047638
UniProt Q96RI1 Q60641
RefSeq (mRNA) NM_001206977 NM_001163504
RefSeq (protein) NP_001193906 NP_001156976
Location (UCSC) Chr 12:
100.47 – 100.56 Mb
Chr 10:
89.45 – 89.53 Mb
PubMed search [1] [2]

The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member 4) is a nuclear receptor that is encoded by the NR1H4 gene in humans.[1][2]


FXR is expressed at high levels in the liver and intestine. Chenodeoxycholic acid and other bile acids are natural ligands for FXR. Similar to other nuclear receptors, when activated, FXR translocates to the cell nucleus, forms a dimer (in this case a heterodimer with RXR) and binds to hormone response elements on DNA, which up- or down-regulates the expression of certain genes.[2]

One of the primary functions of FXR activation is the suppression of cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis from cholesterol. FXR does not directly bind to the CYP7A1 promoter. Rather, FXR induces expression of small heterodimer partner (SHP), which then functions to inhibit transcription of the CYP7A1 gene. In this way a negative feedback pathway is established in which synthesis of bile acids is inhibited when cellular levels are already high. FXR has also been found to be important in regulation of hepatic triglyceride levels.[3] Studies have also shown the FXR to regulate the expression and activity of epithelial transport proteins involved in fluid homestasis in the intestine, such as the cystic fibrosis conductance transmembrane regulator (CFTR).[4]


Farnesoid X receptor has been shown to interact with:


A number of ligands for FXR are known, of both natural and synthetic origin.[7][8][9]



  1. ^ "Entrez Gene: NR1H4 nuclear receptor subfamily 1, group H, member 4". 
  2. ^ a b Forman BM, Goode E, Chen J, Oro AE, Bradley DJ, Perlmann T, Noonan DJ, Burka LT, McMorris T, Lamph WW, Evans RM, Weinberger C (Jun 1995). "Identification of a nuclear receptor that is activated by farnesol metabolites". Cell 81 (5): 687–93. doi:10.1016/0092-8674(95)90530-8. PMID 7774010. 
  3. ^ Jiao Y, Lu Y, Li XY (Jan 2015). "Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis". Acta Pharmacologica Sinica 36 (1): 44–50. doi:10.1038/aps.2014.116. PMID 25500875. 
  4. ^ Mroz MS, Keating N, Ward JB, Sarker R, Amu S, Aviello G, Donowitz M, Fallon PG, Keely SJ (May 2014). "Farnesoid X receptor agonists attenuate colonic epithelial secretory function and prevent experimental diarrhoea in vivo". Gut 63 (5): 808–17. doi:10.1136/gutjnl-2013-305088. PMID 23916961. 
  5. ^ Zhang Y, Castellani LW, Sinal CJ, Gonzalez FJ, Edwards PA (Jan 2004). "Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) regulates triglyceride metabolism by activation of the nuclear receptor FXR". Genes & Development 18 (2): 157–69. doi:10.1101/gad.1138104. PMC 324422. PMID 14729567. 
  6. ^ Seol W, Choi HS, Moore DD (Jan 1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors". Molecular Endocrinology 9 (1): 72–85. doi:10.1210/mend.9.1.7760852. PMID 7760852. 
  7. ^ Fiorucci S, Zampella A, Distrutti E (2012). "Development of FXR, PXR and CAR agonists and antagonists for treatment of liver disorders". Current Topics in Medicinal Chemistry 12 (6): 605–24. doi:10.2174/156802612799436678. PMID 22242859. 
  8. ^ Fiorucci S, Mencarelli A, Distrutti E, Zampella A (May 2012). "Farnesoid X receptor: from medicinal chemistry to clinical applications". Future Medicinal Chemistry 4 (7): 877–91. doi:10.4155/fmc.12.41. PMID 22571613. 
  9. ^ Vaz B, de Lera ÁR (Nov 2012). "Advances in drug design with RXR modulators". Expert Opinion on Drug Discovery 7 (11): 1003–16. doi:10.1517/17460441.2012.722992. PMID 22954251. 
  10. ^ Ricketts ML, Boekschoten MV, Kreeft AJ, Hooiveld GJ, Moen CJ, Müller M, Frants RR, Kasanmoentalib S, Post SM, Princen HM, Porter JG, Katan MB, Hofker MH, Moore DD (Jul 2007). "The cholesterol-raising factor from coffee beans, cafestol, as an agonist ligand for the farnesoid and pregnane X receptors". Molecular Endocrinology 21 (7): 1603–16. doi:10.1210/me.2007-0133. PMID 17456796. 

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