Farnesoid X receptor
Target has curated data in GtoImmuPdb
Target id: 603
Nomenclature: Farnesoid X receptor
Systematic Nomenclature: NR1H4
Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Selected 3D Structures
- Natural/Endogenous Ligands
- Rank order lists
- Agonists
- Antagonists
- Immunopharmacology Comments
- DNA Binding
- Main Co-regulators
- Main Target Genes
- Tissue Distribution
- Physiological Consequences of Altering Gene Expression
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
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| Species | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 486 | 12q23.1 | NR1H4 | nuclear receptor subfamily 1 group H member 4 | 11 |
| Mouse | 484 | 10 44.98 cM | Nr1h4 | nuclear receptor subfamily 1, group H, member 4 | 44 |
| Rat | 469 | 7q13 | Nr1h4 | nuclear receptor subfamily 1, group H, member 4 | 11 |
| Previous and Unofficial Names |
| FXR | HRR1 | RIP14 | Bile acid receptor | FXRα | farnesoid X activated receptor | farnesol receptor HRR-1 | retinoid X receptor-interacting protein 14 | RXR-interacting protein 14 | Rxrip14 | nuclear receptor subfamily 1 |
| Database Links |
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| Alphafold | Q96RI1 (Hs), Q3V1T8 (Mm), Q62735 (Rn) |
| CATH/Gene3D | 3.30.50.10 |
| ChEMBL Target | CHEMBL2047 (Hs), CHEMBL4105917 (Rn) |
| Ensembl Gene | ENSG00000012504 (Hs), ENSMUSG00000047638 (Mm), ENSRNOG00000007197 (Rn) |
| Entrez Gene | 9971 (Hs), 20186 (Mm), 60351 (Rn) |
| Human Protein Atlas | ENSG00000012504 (Hs) |
| KEGG Gene | hsa:9971 (Hs), mmu:20186 (Mm), rno:60351 (Rn) |
| OMIM | 603826 (Hs) |
| Orphanet | ORPHA304804 (Hs) |
| Pharos | Q96RI1 (Hs) |
| RefSeq Nucleotide | NM_005123 (Hs), NM_009108 (Mm), NM_001163504 (Mm), NM_001163700 (Mm), NM_021745 (Rn) |
| RefSeq Protein | NP_005114 (Hs), NP_001157172 (Mm), NP_001156976 (Mm), NP_033134 (Mm), NP_068513 (Rn) |
| SynPHARM |
6410 (in complex with chenodeoxycholic acid) 6415 (in complex with fexaramine) 6414 (in complex with GW4064) |
| UniProtKB | Q96RI1 (Hs), Q3V1T8 (Mm), Q62735 (Rn) |
| Wikipedia | NR1H4 (Hs) |
| Selected 3D Structures |
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| Natural/Endogenous Ligands |
| chenodeoxycholic acid |
| cholic acid |
| deoxycholic acid |
| lithocholic acid |
| 22R-hydroxycholesterol |
| Comments: A series of bile acids are natural ligands |
| Potency order (Human) |
| chenodeoxycholic acid > lithocholic acid, deoxycholic acid [30,35] |
Download all structure-activity data for this target as a CSV file 
| Agonists |
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific agonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonists |
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Immunopharmacology Comments |
FXR is predominantly expressed in liver, intestine, kidney and adipose tissue, but has also been detected in immune cells (CD4+, CD8+, CD19+ and CD14+ cells) [43], albeit at much lower levels than in the primary sites of expression.FXR in inflammation:FXR protects against innate intestinal and hepatic inflammation in animal models.FXR expression is reduced in biopsy specimens from patients with the autoimmine conditions systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD). FXR activation in human monocytes (from healthy controls and MS patients) induces an anti-inflammatory phenotype facilitating control of effector T cell proliferation [16], suggesting that FXR has a regulatory effect in the control of T cell-mediated autoimmunity. This effect is IL-10 dependent. |
| DNA Binding |
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| DNA Binding Comments | |||||||
| FXR binds IR1 | |||||||
| Main Co-regulators |
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| Name | Activity | Specific | Ligand dependent | AF-2 dependent | Comments | References |
| PPARGC1A | Co-activator | No | Yes | Yes | 20,41,51 | |
| NCOA1 | Co-activator | No | Yes | Yes | 30,35 | |
| MED1 | Co-activator | No | Yes | Yes | 37 | |
| CARM1 | Co-activator | No | Yes | Yes | 1 | |
| PRMT1 | Co-activator | No | Yes | No | 40 | |
| TRRAP | Co-activator | No | Yes | No | 47 | |
| Main Target Genes |
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| Name | Species | Effect | Technique | Comments | References |
| VLDLR | Human | Activated | 6 | ||
| NR0B2 | Human | Activated | Transient transfection, EMSA | NR0B2 is a nuclear receptor also commonly known as short heterodimer partner (SHP) | 13,27 |
| ABCB11 | Human | Activated | Transient transfection, EMSA | progressive familial intrahepatic cholestasis 2, bile salt export pump | 1 |
| FABP6 | Human | Activated | Transient transfection, EMSA | Fatty acid binding protein 6, ileal | 14 |
| ABCB4 | Human | Activated | Transient transfection, EMSA | 7 | |
| FGF19 | Human | Activated | Transient transfection, EMSA | 15 | |
| ABCC2 | Human | Activated | Transient transfection, EMSA | multidrug resistance associated protein 2 (MRP2multidrug resistance associated protein 2 (MRP2) | 29 |
| SLCO1B3 | Human | Activated | Transient transfection, EMSA | solute carrier organic anion transporter family member 1B3 (OATP1B3; SLCO1B3) | 19 |
| SLC27A5 | Human | Activated | Transient transfection, EMSA | bile acid-CoA synthetase (BACS) | 38 |
| SLC3A1 | Human | Activated | Transient transfection, EMSA | bile acid-CoA: amino acid N-acetyltransferase (BAT) | 38 |
| APOAI | Human | Repressed | Transient transfection, EMSA | apolipoprotein A-I (APOAI): Repressed by FXR binding as a monomer to negative FXR response element. | 6 |
| APOC2 | Human | Repressed | Transient transfection, EMSA | apolipoprotein C-II (ApoCII) | 21 |
| APOE | Human | Activated | APOE- apolipoprotein E. | 29 | |
| C3 | Human | Activated | Transient transfection, EMSA | complement component 3 | 26 |
| PDK4 | Human | Activated | pyruvate dehydrogenase kinase, isozyme 4 | 41 | |
| PLTP | Human | Activated | Transient transfection, EMSA | phospholipid transfer protein | 48 |
| PPARA | Human | Activated | Transient transfection, EMSA | The mouse PPARa gene is not induced. | 37 |
| Fibrinogen | Human | Activated | 2 | ||
| KNG1 | Human | Activated | Transient transfection, EMSA | 7 | |
| SDC1 | Human | Activated | Transient transfection, EMSA | CD138, syndecan-1, SYND1 | 9 |
| VIPR1 | Human | Activated | 5 | ||
| alpha-crystallin | Human | Activated | Transient transfection, EMSA | 25 | |
| organic solute transporter α-β | Human | Activated | 12,24,53 | ||
| Abcb4 | Mouse | Activated | Transient transfection, EMSA | 17-18 | |
| Apoc3 | Mouse | Repressed | ChIP, Transient transfection, EMSA | 6 | |
| Tissue Distribution
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| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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| Clinically-Relevant Mutations and Pathophysiology
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References
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2. Anisfeld AM, Kast-Woelbern HR, Lee H, Zhang Y, Lee FY, Edwards PA. (2005) Activation of the nuclear receptor FXR induces fibrinogen expression: a new role for bile acid signaling. J Lipid Res, 46 (3): 458-68. [PMID:15604525]
3. Carpenter J, Wu G, Wang Y, Cook EM, Wang T, Sitkoff D, Rossi KA, Mosure K, Zhuo X, Cao GG et al.. (2021) Discovery of BMS-986318, a Potent Nonbile Acid FXR Agonist for the Treatment of Nonalcoholic Steatohepatitis. ACS Med Chem Lett, 12 (9): 1413-1420. [PMID:34531950]
4. Chianelli D, Rucker PV, Roland J, Tully DC, Nelson J, Liu X, Bursulaya B, Hernandez ED, Wu J, Prashad M et al.. (2020) Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis. J Med Chem, 63 (8): 3868-3880. [PMID:31940200]
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6. Claudel T, Sturm E, Duez H, Torra IP, Sirvent A, Kosykh V, Fruchart JC, Dallongeville J, Hum DW, Kuipers F, Staels B. (2002) Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element. J Clin Invest, 109 (7): 961-71. [PMID:11927623]
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33. Mo C, Xu X, Zhang P, Peng Y, Zhao X, Chen S, Guo F, Xiong Y, Chu XJ, Xu X. (2023) Discovery of HPG1860, a Structurally Novel Nonbile Acid FXR Agonist Currently in Clinical Development for the Treatment of Nonalcoholic Steatohepatitis. J Med Chem, 66 (14): 9363-9375. [PMID:37424079]
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