Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene information from NCBI Gene database. Gene SNPs miRNA Transcription factors Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID	9971
Gene name	Nuclear receptor subfamily 1 group H member 4
Gene symbol	NR1H4
Synonyms (NCBI Gene)	BARFXRHRR-1HRR1PFIC5RIP14
Chromosome	12
Chromosome location	12q23.1
Summary	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

Show/Hide all (10)

SNP ID	Visualize variation	Clinical significance	Consequence
rs113090017	C>A,G,T	Pathogenic	Synonymous variant, non coding transcript variant, stop gained, intron variant, coding sequence variant, missense variant
rs137946171	G>A	Conflicting-interpretations-of-pathogenicity	Non coding transcript variant, coding sequence variant, synonymous variant
rs140648896	T>C	Conflicting-interpretations-of-pathogenicity	Synonymous variant, genic upstream transcript variant, non coding transcript variant, coding sequence variant
rs770757947	->A	Likely-pathogenic	Downstream transcript variant, coding sequence variant, non coding transcript variant, frameshift variant, genic downstream transcript variant
rs879255644	->AAA	Pathogenic	Inframe insertion, non coding transcript variant, coding sequence variant
rs1322754256	C>A,T	Conflicting-interpretations-of-pathogenicity	Non coding transcript variant, coding sequence variant, missense variant, synonymous variant
rs1555335324	C>T	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant, intron variant
rs1555335782	G>A	Likely-pathogenic	Splice donor variant
rs1566464880	A>G	Likely-pathogenic	Missense variant, coding sequence variant, splice acceptor variant, non coding transcript variant
rs1593114820	C>-	Likely-pathogenic	Coding sequence variant, non coding transcript variant, genic downstream transcript variant, frameshift variant

Show/Hide all (21)

miRTarBase ID	miRNA	Experiments	Reference
MIRT054133	hsa-miR-92a-3p	Luciferase reporter assayqRT-PCRWestern blot	25095974
MIRT054133	hsa-miR-92a-3p	Luciferase reporter assayqRT-PCRWestern blot	25095974
MIRT731905	hsa-miR-192-3p	Luciferase reporter assay	27079614
MIRT731905	hsa-miR-192-3p	Luciferase reporter assay	27079614
MIRT756465	hsa-miR-382-5p	Luciferase reporter assay	34712060
MIRT1192152	hsa-miR-28-5p	CLIP-seq
MIRT1192153	hsa-miR-3139	CLIP-seq
MIRT1192154	hsa-miR-4517	CLIP-seq
MIRT1192155	hsa-miR-4633-3p	CLIP-seq
MIRT1192156	hsa-miR-4712-3p	CLIP-seq
MIRT1192157	hsa-miR-708	CLIP-seq
MIRT2582440	hsa-miR-3938	CLIP-seq
MIRT2582441	hsa-miR-4254	CLIP-seq
MIRT2582442	hsa-miR-4292	CLIP-seq
MIRT2582443	hsa-miR-4308	CLIP-seq
MIRT2582444	hsa-miR-670	CLIP-seq
MIRT2582440	hsa-miR-3938	CLIP-seq
MIRT2582441	hsa-miR-4254	CLIP-seq
MIRT2582442	hsa-miR-4292	CLIP-seq
MIRT2582443	hsa-miR-4308	CLIP-seq
MIRT2582444	hsa-miR-670	CLIP-seq

Show/Hide all (5)

Transcription factor	Regulation	Reference
EP300	Repression	18842595
IRF6	Unknown	12525500
IRF7	Unknown	23372731
NR0B1	Repression	21856289
STAT1	Repression	19393742

113

Show/Hide all (113)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IBA
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	ISS	21757002
GO:0000785	Component	Chromatin	IC	27471003
GO:0000785	Component	Chromatin	ISA
GO:0000791	Component	Euchromatin	IDA	21757002
GO:0000976	Function	Transcription cis-regulatory region binding	IMP	26888176
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	23767959
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	21757002
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IDA	21757002
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001221	Function	Transcription coregulator binding	IPI	14701856
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	21757002, 24211198, 27471003
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IEA
GO:0001678	Process	Intracellular glucose homeostasis	IEA
GO:0002376	Process	Immune system process	IEA
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0003700	Function	DNA-binding transcription factor activity	TAS	9223286
GO:0004879	Function	Nuclear receptor activity	IBA
GO:0004879	Function	Nuclear receptor activity	IDA	27471003
GO:0004879	Function	Nuclear receptor activity	IEA
GO:0004879	Function	Nuclear receptor activity	TAS	10334993
GO:0005515	Function	Protein binding	IPI	12917342, 14684751, 14698205, 15317749, 18391212, 19833092, 21532585, 22345554, 25675114, 26871637, 28514442, 32296183
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005829	Component	Cytosol	IDA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IMP	26888176
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IDA	10334992
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IEA
GO:0006366	Process	Transcription by RNA polymerase II	IEA
GO:0006954	Process	Inflammatory response	IEA
GO:0007043	Process	Cell-cell junction assembly	IEA
GO:0007219	Process	Notch signaling pathway	IEA
GO:0008206	Process	Bile acid metabolic process	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0010558	Process	Negative regulation of macromolecule biosynthetic process	IEA
GO:0010804	Process	Negative regulation of tumor necrosis factor-mediated signaling pathway	IEA
GO:0010903	Process	Negative regulation of very-low-density lipoprotein particle remodeling	IDA	27471003
GO:0010903	Process	Negative regulation of very-low-density lipoprotein particle remodeling	IEA
GO:0010988	Process	Regulation of low-density lipoprotein particle clearance	IDA	12660231
GO:0015721	Process	Bile acid and bile salt transport	TAS
GO:0016607	Component	Nuclear speck	IDA
GO:0016922	Function	Nuclear receptor binding	TAS	21757002
GO:0030154	Process	Cell differentiation	IBA
GO:0030522	Process	Intracellular receptor signaling pathway	IBA
GO:0032052	Function	Bile acid binding	IBA
GO:0032052	Function	Bile acid binding	IDA	21757002, 23767959
GO:0032052	Function	Bile acid binding	IEA
GO:0032689	Process	Negative regulation of type II interferon production	IDA	21242261
GO:0032689	Process	Negative regulation of type II interferon production	IEA
GO:0032692	Process	Negative regulation of interleukin-1 production	IEA
GO:0032703	Process	Negative regulation of interleukin-2 production	IEA
GO:0032715	Process	Negative regulation of interleukin-6 production	IEA
GO:0032720	Process	Negative regulation of tumor necrosis factor production	IDA	21242261
GO:0032720	Process	Negative regulation of tumor necrosis factor production	IEA
GO:0032740	Process	Positive regulation of interleukin-17 production	IDA	21242261
GO:0034162	Process	Toll-like receptor 9 signaling pathway	IEA
GO:0034255	Process	Regulation of urea metabolic process	IEA
GO:0034255	Process	Regulation of urea metabolic process	ISS	21757002
GO:0035356	Process	Intracellular triglyceride homeostasis	IDA	20447400
GO:0035774	Process	Positive regulation of insulin secretion involved in cellular response to glucose stimulus	IEA
GO:0038185	Process	Nuclear receptor-mediated bile acid signaling pathway	IDA	10334992, 21757002
GO:0038185	Process	Nuclear receptor-mediated bile acid signaling pathway	IEA
GO:0038185	Process	Nuclear receptor-mediated bile acid signaling pathway	TAS	23767959
GO:0038186	Function	Bile acid nuclear receptor activity	IDA	10334992, 21757002, 23767959
GO:0038186	Function	Bile acid nuclear receptor activity	IEA
GO:0038186	Function	Bile acid nuclear receptor activity	TAS
GO:0042593	Process	Glucose homeostasis	IEA
GO:0042632	Process	Cholesterol homeostasis	IBA
GO:0042632	Process	Cholesterol homeostasis	IEA
GO:0042742	Process	Defense response to bacterium	IEA
GO:0043066	Process	Negative regulation of apoptotic process	IDA	20447400
GO:0043124	Process	Negative regulation of canonical NF-kappaB signal transduction	IDA	21242261
GO:0043124	Process	Negative regulation of canonical NF-kappaB signal transduction	IEA
GO:0043235	Component	Receptor complex	IDA	10334992
GO:0043565	Function	Sequence-specific DNA binding	IDA	12815072
GO:0043565	Function	Sequence-specific DNA binding	IEA
GO:0045087	Process	Innate immune response	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	IDA	27471003
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	23767959
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	21757002
GO:0046628	Process	Positive regulation of insulin receptor signaling pathway	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0046965	Function	Nuclear retinoid X receptor binding	IEA
GO:0050728	Process	Negative regulation of inflammatory response	IBA
GO:0050728	Process	Negative regulation of inflammatory response	IEA
GO:0055089	Process	Fatty acid homeostasis	IEA
GO:0061178	Process	Regulation of insulin secretion involved in cellular response to glucose stimulus	IDA	20447400
GO:0070328	Process	Triglyceride homeostasis	IEA
GO:0070857	Process	Regulation of bile acid biosynthetic process	TAS	21757002
GO:0071222	Process	Cellular response to lipopolysaccharide	IEA
GO:0071398	Process	Cellular response to fatty acid	IDA	20447400
GO:0071638	Process	Negative regulation of monocyte chemotactic protein-1 production	IEA
GO:0090181	Process	Regulation of cholesterol metabolic process	TAS	21757002
GO:0090575	Component	RNA polymerase II transcription regulator complex	IBA
GO:1902122	Function	Chenodeoxycholic acid binding	IDA	10334992
GO:1903413	Process	Cellular response to bile acid	IDA	10334992, 21757002
GO:1903413	Process	Cellular response to bile acid	IEA
GO:1903413	Process	Cellular response to bile acid	IMP	23767959
GO:1904179	Process	Positive regulation of adipose tissue development	IEA
GO:1905695	Process	Positive regulation of phosphatidic acid biosynthetic process	IDA	23767959
GO:2000213	Process	Positive regulation of glutamate metabolic process	IEA
GO:2000213	Process	Positive regulation of glutamate metabolic process	ISS	21757002
GO:2001250	Process	Positive regulation of ammonia assimilation cycle	IEA

MIM	HGNC	e!Ensembl
603826	7967	ENSG00000012504

Q96RI1

Protein 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)

Protein function

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 gen

PDB

1OSH , 3BEJ , 3DCT , 3DCU , 3FLI , 3FXV , 3GD2 , 3HC5 , 3HC6 , 3L1B , 3OKH , 3OKI , 3OLF , 3OMK , 3OMM , 3OOF , 3OOK , 3P88 , 3P89 , 3RUT , 3RUU , 3RVF , 4OIV , 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

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF00105	zf-C4	135 → 204	Zinc finger, C4 type (two domains)	Domain
PF00104	Hormone_recep	289 → 471	Ligand-binding domain of nuclear hormone receptor	Domain

Tissue specificity

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

MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAKGVLTEQVAGPLGQNLEVEPYSQYS
NVQFPQVQPQISSSSYYSNLGFYPQQPEEWYSPGIYELRRMPAETLYQGETEVAEMPVTK
KPRMGASAGRIKGDELCVVCGDRASGYHYNALTCEGCKGFFRRSITKNAVYKCKNGGNCV
MDMYMRRKCQECRLRKCKEMGMLAECMYTGLLTEIQCKSKRLRKNVKQHADQTVNEDSEG
RDLRQVTSTTKSCREKTELTPDQQTLLHFIMDSYNKQRMPQEITNKILKEEFSAEENFLI
LTEMATNHVQVLVEFTKKLPGFQTLDHEDQIALLKGSAVEAMFLRSAEIFNKKLPSGHSD
LLEERIRNSGISDEYITPMFSFYKSIGELKMTQEEYALLTAIVILSPDRQYIKDREAVEK
LQEPLLDVLQKLCKIHQPENPQHFACLLGRLTELRTFNHHHAEMLMSWRVNDHKFTPLLC
EIWDVQ

Sequence length

486

Interactions

View interactions

	KEGG		Reactome
	Bile secretion		Recycling of bile acids and salts Synthesis of bile acids and bile salts Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol Synthesis of bile acids and bile salts via 27-hydroxycholesterol PPARA activates gene expression Endogenous sterols Nuclear Receptor transcription pathway SUMOylation of intracellular receptors

Show/Hide Causal Diseases (3)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
Cholestasis, progressive familial intrahepatic, 5	Likely pathogenic; Pathogenic	rs1251445242, rs1555335782, rs879255644, rs113090017, rs2500820482, rs2500723504, rs1313639936, rs1593114820	RCV001824258 RCV002244148 RCV000239480 RCV000239570 RCV003492890 RCV003492891 RCV004557240 RCV005860114 RCV000991448
NR1H4-related disorder	Pathogenic; Likely pathogenic	rs879255644, rs113090017, rs1555335782	RCV004754355 RCV004754356 RCV004754482
Progressive familial intrahepatic cholestasis type 1	Pathogenic	rs879255644, rs113090017	RCV000240839 RCV000240831

Show/Hide Unknown Diseases (6)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Unknown Diseases with uncertain, conflicting, or no pathogenic evidence in ClinVar
Cholangiocarcinoma	Benign	rs7973216	RCV005923511
Familial cancer of breast	Uncertain significance	rs150295715	RCV005897249
Gastric cancer	Benign	rs7973216, rs11110413	RCV005923508 RCV005892813
Lung cancer	Benign	rs7973216, rs11110413	RCV005923512 RCV005892814
Ovarian serous cystadenocarcinoma	Benign	rs7973216	RCV005923509
Thymoma	Benign	rs7973216	RCV005923510

Show/Hide Text Mining Associations (102)

Disease Name	Relationship Type	References
Associations from Text MiningDisease associations identified through Pubtator
Adenocarcinoma	Stimulate	17054793
Adenocarcinoma	Associate	27510297
Ascites	Associate	31062417
Asthma	Associate	31670489
Barrett Esophagus	Stimulate	17054793
Barrett Esophagus	Associate	27511066
Blind Loop Syndrome	Inhibit	23189156
Blood Coagulation Disorders	Associate	26888176
Breast Neoplasms	Associate	16439808, 17047076, 21499302, 26545738, 32650752
Carbamoyl Phosphate Synthase I Deficiency Disease	Associate	31062417
Carcinogenesis	Associate	27079614, 30787420, 35449124
Carcinogenesis	Inhibit	34995680
Carcinoma Hepatocellular	Associate	15604525, 22446874, 23680185, 26165647, 28496032, 28970500, 29958417, 36982249, 37774075
Carcinoma Hepatocellular	Inhibit	30787420, 34995680
Carcinoma Non Small Cell Lung	Associate	28377627, 35211760
Carcinoma Renal Cell	Associate	28496032, 36123627
Carcinoma Renal Cell	Inhibit	35931808
Carcinoma Squamous Cell	Associate	23341777
Carcinoma Squamous Cell	Inhibit	35347542
Cerebral Hemorrhage	Associate	38266922
Chemical and Drug Induced Liver Injury	Associate	27976737
Cholangitis Sclerosing	Associate	28008998
Cholestasis	Associate	19187229, 26888176, 28008998, 30778102, 30964181, 32001325
Cholestasis	Inhibit	25798860
Colitis	Associate	23189156
Colitis Ulcerative	Associate	22929053, 35348180
Colonic Neoplasms	Associate	24177031, 27079614
Colorectal Neoplasms	Associate	24177031, 25596928, 32299194, 34995680, 35348180, 35449124, 36129029
Colorectal Neoplasms	Inhibit	36340269
COVID 19	Associate	37697930
Crohn Disease	Inhibit	21887309, 23189156
Crohn Disease	Associate	32024859, 32678214
Diabetes Mellitus	Associate	19059462, 29717168
Diabetes Mellitus	Inhibit	35348180
Diabetes Mellitus Type 2	Associate	35046895, 38309826
Diabetic Nephropathies	Associate	37337149
Dyslipidemias	Associate	29717168
End Stage Liver Disease	Associate	26888176, 31062417
Enteritis	Inhibit	34995680
Enterocolitis Necrotizing	Associate	36371157
Esophageal Squamous Cell Carcinoma	Stimulate	33686512
Esophagitis	Stimulate	17054793
Fatty Liver	Associate	26019035, 36735888
Fatty Liver Alcoholic	Stimulate	26019035
Fatty Liver Alcoholic	Associate	29717168, 31388096, 31670489
Fibrosis	Inhibit	22265968, 27853248
Fibrosis	Associate	38266922
Fragile X Syndrome	Associate	8668200
Gallbladder Neoplasms	Associate	27167107
Gallstones	Associate	15810076, 32597704
Gastroesophageal Reflux	Associate	33686512
Genetic Diseases Inborn	Associate	19228886
Graft vs Host Disease	Associate	38429422
Heart Failure	Associate	31062417
HIV Infections	Inhibit	23106848
Hyperbilirubinemia	Associate	27510297
Hyperglycemia	Associate	30397356
Hypertension Portal	Associate	31062417
Hypertriglyceridemia	Associate	12519787
Hypoxia	Inhibit	19187229
Idiopathic Noncirrhotic Portal Hypertension	Associate	26293907
Infant Newborn Diseases	Associate	26888176
Inflammation	Inhibit	21887309, 27976737, 34995680
Inflammation	Associate	21887309, 22929053, 23189156, 27106679, 27432520, 31062417, 31173497, 33686512, 35348180, 38429422
Inflammatory Bowel Diseases	Inhibit	21887309, 32024859
Inflammatory Bowel Diseases	Associate	21887309, 22929053, 39490736
Intestinal Diseases	Associate	34510400, 39490736
Intrahepatic Cholestasis of Pregnancy	Associate	24366234, 24498169, 26888176, 31482549, 35436901
Irritable Bowel Syndrome	Associate	24763552
Irritable Bowel Syndrome	Inhibit	35348180
Ischemia	Associate	19187229
Kidney Diseases	Inhibit	27853248
Lead Poisoning Nervous System	Associate	36558100
Liver Cirrhosis Biliary	Associate	26293907, 30275017
Liver Diseases	Associate	19059462, 29717168, 31062417, 31670489, 36558100, 37208429
Liver Failure	Associate	19187229
Liver Neoplasms	Associate	23680185, 37774075
Lymphatic Metastasis	Stimulate	21364590, 23653380
Malformations of Cortical Development Group I	Associate	37337149
Maturity Onset Diabetes of the Young Type 3	Associate	23607861
Metabolic Diseases	Associate	25725071, 30397356, 31670489
Mitochondrial Diseases	Inhibit	22265968
Multiple Myeloma	Associate	25669983
Mycosis Fungoides	Associate	33299887
Neoplasm Metastasis	Stimulate	32650752
Neoplasms	Associate	22446874, 27006468, 27079614, 28496032, 31779647, 32299194, 32650752, 33488300, 35347542, 35563650, 36123627, 36340269, 36834607
Neoplasms	Inhibit	24177031, 27167107, 28377627, 28970500, 34995680, 35348180
Neoplasms	Stimulate	28402278
Non alcoholic Fatty Liver Disease	Associate	26019035, 29466845, 30275017, 30778102, 34063472, 36735888
Obesity	Inhibit	35348180
Osteosarcoma	Associate	31779647
Pancreatic Neoplasms	Associate	21364590, 23653380, 28402278
Polycystic Ovary Syndrome	Associate	31173497
Precancerous Conditions	Inhibit	24177031
Proteinuria	Associate	35348180
Pulmonary Disease Chronic Obstructive	Associate	36924977
Stomach Neoplasms	Associate	23238937, 25095974, 34510400
Urinary Bladder Neoplasms	Associate	35563650
Uterine Cervical Neoplasms	Inhibit	35347542
Uterine Cervical Neoplasms	Associate	35347542
Wounds and Injuries	Associate	22265968
Xanthomatosis Cerebrotendinous	Associate	15576845

NR1H4 (nuclear receptor subfamily 1 group H member 4)