• Gene id: 9971

Gene Summary

• Gene Symbol: NR1H4   Gene   UCSC   Ensembl
• Aliases: BAR, FXR, HRR-1, HRR1, PFIC5, RIP14
• Gene name: nuclear receptor subfamily 1 group H member 4
• Alternate names: bile acid receptor, RXR-interacting protein 14, farnesoid X nuclear receptor, farnesoid X-activated receptor, farnesol receptor HRR-1, retinoid X receptor-interacting protein 14,
• Gene location: 12q23.1 (100473865: 100564413)     Exons: 21     NC_000012.12
• Gene summary(Entrez): 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
• OMIM: 603826

Protein Summary

• Protein general information: Q96RI1  
  • Name: 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)
  • Length: 486  
  • Mass: 55914
  • Tissue specificity: Liver and hepatocyte-related cells express mainly FXRalpha1-type isoforms with isoform 3 and isoform 4 in approximately equal proportions. In intestine and kidney mainly FXRalpha2-type isoforms are expressed with isoform 1 and isoform
• Sequence:

  MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAKGVLTEQVAGPLGQNLEVEPYSQYSNVQFPQVQPQISSSS
  YYSNLGFYPQQPEEWYSPGIYELRRMPAETLYQGETEVAEMPVTKKPRMGASAGRIKGDELCVVCGDRASGYHYN
  ALTCEGCKGFFRRSITKNAVYKCKNGGNCVMDMYMRRKCQECRLRKCKEMGMLAECMYTGLLTEIQCKSKRLRKN
  VKQHADQTVNEDSEGRDLRQVTSTTKSCREKTELTPDQQTLLHFIMDSYNKQRMPQEITNKILKEEFSAEENFLI
  LTEMATNHVQVLVEFTKKLPGFQTLDHEDQIALLKGSAVEAMFLRSAEIFNKKLPSGHSDLLEERIRNSGISDEY
  ITPMFSFYKSIGELKMTQEEYALLTAIVILSPDRQYIKDREAVEKLQEPLLDVLQKLCKIHQPENPQHFACLLGR
  LTELRTFNHHHAEMLMSWRVNDHKFTPLLCEIWDVQ

• Structural information:
  • Protein Domains: (262..48-)
    (/note="NR-LBD)
    (/evidence="ECO:0000255|PROSITE-ProRule:PRU01189"-)
  • Interpro: IPR035500  IPR000536  IPR001723  IPR001728  IPR001628   IPR013088  
  • Prosite: PS51843 PS00031 PS51030
  • PDB: 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 5IAW 5ICK 5Q0I 5Q0J 5Q0K 5Q0L 5Q0M 5Q0N 5Q0O 5Q0P 5Q0Q 5Q0R 5Q0S 5Q0T 5Q0U 5Q0V 5Q0W 5Q0X 5Q0Y 5Q0Z 5Q10 5Q11 5Q12 5Q13 5Q14 5Q15 5Q16 5Q17 5Q18 5Q19 5Q1A 5Q1B 5Q1C 5Q1D 5Q1E 5Q1F 5Q1
  • 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 5IAW 5ICK 5Q0I 5Q0J 5Q0K 5Q0L 5Q0M 5Q0N 5Q0O 5Q0P 5Q0Q 5Q0R 5Q0S 5Q0T 5Q0U 5Q0V 5Q0W 5Q0X 5Q0Y 5Q0Z 5Q10 5Q11 5Q12 5Q13 5Q14 5Q15 5Q16 5Q17 5Q18 5Q19 5Q1A 5Q1B 5Q1C 5Q1D 5Q1E 5Q1F 5Q1
  • DIP: 39370
  • STRING: ENSP00000447149
• Other Databases: GeneCards:  NR1H4  Malacards:  NR1H4

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0004879	nuclear receptor activity	IDA	molecular function
GO:0000977	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	molecular function
GO:0038181	bile acid receptor activity	TAS	molecular function
GO:1905695	positive regulation of phosphatidic acid biosynthetic process	IDA	biological process
GO:0045944	positive regulation of transcription by RNA polymerase II	IDA	biological process
GO:0038183	bile acid signaling pathway	TAS	biological process
GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	ISM	molecular function
GO:0000790	nuclear chromatin	ISA	cellular component
GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA	molecular function
GO:0090575	RNA polymerase II transcription regulator complex	IBA	cellular component
GO:0042632	cholesterol homeostasis	IBA	biological process
GO:0038181	bile acid receptor activity	IBA	molecular function
GO:0038023	signaling receptor activity	IBA	molecular function
GO:0032052	bile acid binding	IBA	molecular function
GO:0030154	cell differentiation	IBA	biological process
GO:0004879	nuclear receptor activity	IBA	molecular function
GO:0055088	lipid homeostasis	IBA	biological process
GO:0050728	negative regulation of inflammatory response	IBA	biological process
GO:0045944	positive regulation of transcription by RNA polymerase II	IBA	biological process
GO:0038183	bile acid signaling pathway	IBA	biological process
GO:0008134	transcription factor binding	IBA	molecular function
GO:0006629	lipid metabolic process	IBA	biological process
GO:0000977	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA	molecular function
GO:0000122	negative regulation of transcription by RNA polymerase II	IBA	biological process
GO:1902714	negative regulation of interferon-gamma secretion	IDA	biological process
GO:0043124	negative regulation of I-kappaB kinase/NF-kappaB signaling	IDA	biological process
GO:0043066	negative regulation of apoptotic process	IDA	biological process
GO:0071398	cellular response to fatty acid	IDA	biological process
GO:0035356	cellular triglyceride homeostasis	IDA	biological process
GO:1904468	negative regulation of tumor necrosis factor secretion	IDA	biological process
GO:0072615	interleukin-17 secretion	IDA	biological process
GO:0034142	toll-like receptor 4 signaling pathway	IDA	biological process
GO:0010988	regulation of low-density lipoprotein particle clearance	IDA	biological process
GO:0034971	histone H3-R17 methylation	IDA	biological process
GO:0061178	regulation of insulin secretion involved in cellular response to glucose stimulus	IDA	biological process
GO:0005515	protein binding	IPI	molecular function
GO:0003700	DNA-binding transcription factor activity	IEA	molecular function
GO:0003707	steroid hormone receptor activity	IEA	molecular function
GO:0004879	nuclear receptor activity	IEA	molecular function
GO:0008270	zinc ion binding	IEA	molecular function
GO:0042025	host cell nucleus	IEA	cellular component
GO:0043565	sequence-specific DNA binding	IEA	molecular function
GO:0003677	DNA binding	IEA	molecular function
GO:0006355	regulation of transcription, DNA-templated	IEA	biological process
GO:0002376	immune system process	IEA	biological process
GO:0046872	metal ion binding	IEA	molecular function
GO:0045087	innate immune response	IEA	biological process
GO:0006954	inflammatory response	IEA	biological process
GO:0005634	nucleus	IEA	cellular component
GO:0003677	DNA binding	IEA	molecular function
GO:0003700	DNA-binding transcription factor activity	TAS	molecular function
GO:0004879	nuclear receptor activity	TAS	molecular function
GO:0001228	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	molecular function
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0006367	transcription initiation from RNA polymerase II promoter	TAS	biological process
GO:0015721	bile acid and bile salt transport	TAS	biological process
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0003700	DNA-binding transcription factor activity	IEA	molecular function
GO:0004879	nuclear receptor activity	IEA	molecular function
GO:0006357	regulation of transcription by RNA polymerase II	IEA	biological process
GO:0007219	Notch signaling pathway	IEA	biological process
GO:0010804	negative regulation of tumor necrosis factor-mediated signaling pathway	IEA	biological process
GO:0030522	intracellular receptor signaling pathway	IEA	biological process
GO:0032052	bile acid binding	IEA	molecular function
GO:0032692	negative regulation of interleukin-1 production	IEA	biological process
GO:0032703	negative regulation of interleukin-2 production	IEA	biological process
GO:0032720	negative regulation of tumor necrosis factor production	IEA	biological process
GO:0035774	positive regulation of insulin secretion involved in cellular response to glucose stimulus	IEA	biological process
GO:0042593	glucose homeostasis	IEA	biological process
GO:0042632	cholesterol homeostasis	IEA	biological process
GO:0043124	negative regulation of I-kappaB kinase/NF-kappaB signaling	IEA	biological process
GO:0070328	triglyceride homeostasis	IEA	biological process
GO:0071222	cellular response to lipopolysaccharide	IEA	biological process
GO:0071638	negative regulation of monocyte chemotactic protein-1 production	IEA	biological process
GO:2000213	positive regulation of glutamate metabolic process	IEA	biological process
GO:2001250	positive regulation of ammonia assimilation cycle	IEA	biological process
GO:0000122	negative regulation of transcription by RNA polymerase II	IEA	biological process
GO:0001678	cellular glucose homeostasis	IEA	biological process
GO:0007043	cell-cell junction assembly	IEA	biological process
GO:0008206	bile acid metabolic process	IEA	biological process
GO:0032088	negative regulation of NF-kappaB transcription factor activity	IEA	biological process
GO:0032689	negative regulation of interferon-gamma production	IEA	biological process
GO:0032715	negative regulation of interleukin-6 production	IEA	biological process
GO:0034162	toll-like receptor 9 signaling pathway	IEA	biological process
GO:0034255	regulation of urea metabolic process	IEA	biological process
GO:0038183	bile acid signaling pathway	IEA	biological process
GO:0042742	defense response to bacterium	IEA	biological process
GO:0045944	positive regulation of transcription by RNA polymerase II	IEA	biological process
GO:0046628	positive regulation of insulin receptor signaling pathway	IEA	biological process
GO:0046965	retinoid X receptor binding	IEA	molecular function
GO:0050728	negative regulation of inflammatory response	IEA	biological process
GO:0055089	fatty acid homeostasis	IEA	biological process
GO:0071417	cellular response to organonitrogen compound	IEA	biological process
GO:1904179	positive regulation of adipose tissue development	IEA	biological process
GO:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	molecular function
GO:0001228	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	molecular function
GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	IDA	molecular function
GO:0004879	nuclear receptor activity	ISS	molecular function
GO:0032052	bile acid binding	ISS	molecular function
GO:0032052	bile acid binding	TAS	molecular function
GO:0038183	bile acid signaling pathway	ISS	biological process
GO:0016922	nuclear receptor binding	TAS	molecular function
GO:0001080	nitrogen catabolite activation of transcription from RNA polymerase II promoter	IC	biological process
GO:0005719	nuclear euchromatin	IDA	cellular component
GO:0030522	intracellular receptor signaling pathway	ISS	biological process
GO:0090181	regulation of cholesterol metabolic process	TAS	biological process
GO:2000213	positive regulation of glutamate metabolic process	ISS	biological process
GO:0000122	negative regulation of transcription by RNA polymerase II	ISS	biological process
GO:0034255	regulation of urea metabolic process	ISS	biological process
GO:0045944	positive regulation of transcription by RNA polymerase II	IMP	biological process
GO:0070857	regulation of bile acid biosynthetic process	TAS	biological process
GO:0071417	cellular response to organonitrogen compound	ISS	biological process
GO:0005634	nucleus	IEA	cellular component
GO:0043401	steroid hormone mediated signaling pathway	IEA	biological process
GO:0038185	intracellular bile acid receptor signaling pathway	IDA	biological process
GO:0043565	sequence-specific DNA binding	IDA	molecular function
GO:0038181	bile acid receptor activity	IDA	molecular function
GO:1902122	chenodeoxycholic acid binding	IDA	molecular function
GO:1903413	cellular response to bile acid	IDA	biological process
GO:0043235	receptor complex	IDA	cellular component
GO:0006357	regulation of transcription by RNA polymerase II	IDA	biological process
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function

KEGG pathways

Pathway id	Pathway name
hsa04976	Bile secretion

Diseases

Associated diseases	References
Progressive familial intrahepatic cholestasis	KEGG:H00624
Progressive familial intrahepatic cholestasis	KEGG:H00624
Non-alcoholic steatohepatitis	PMID:28774887
Primary biliary cirrhosis	PMID:29968724
Extrahepatic cholestasis	PMID:22057115
hepatocellular carcinoma	PMID:23213087
hepatocellular carcinoma	PMID:24954587
Aberrant CpGs in Low Motility Sperm	MIK: 21674046
Cryptorchidism	MIK: 28606200
Spermatogenic defects	MIK: 31037746
Teratozoospermia	MIK: 17327269
Unexplained infertility	MIK: 25753583

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
17327269	Teratozoospermia			19 (6 controls, 13 cases)	Male infertility	GSE6872 analyzed by GEO2R (cutoff 1.5 fold)
21674046	Aberrant CpGs in Low Motility Sperm			18	Male infertility	GSE26881
28606200	Cryptorchidism			Monozgotic twins (1 control, I cwith cryptorchidism)	Male infertility	MeDIP-Seq
31037746	Spermatogenic defects			16 (1 control, 15 cases)	Male infertility	GSE6023 analyzed using GEO2R
25753583	Unexplained infertility			46 (17 fertile men, 29 male patients)	Male infertility	Microarray