NR1H4 (nuclear receptor subfamily 1 group H member 4)

Gene

• Entrez ID: 9971
• Gene name: Nuclear receptor subfamily 1 group H member 4
• Gene symbol: NR1H4
• Synonyms: BAR, FXR, HRR-1, HRR1, PFIC5, RIP14
• 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

SNPs

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

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT054133	hsa-miR-92a-3p	Luciferase reporter assay, qRT-PCR, Western blot	25095974
MIRT054133	hsa-miR-92a-3p	Luciferase reporter assay, qRT-PCR, Western 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

Transcription factors

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

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IBA	21873635
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: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	21873635
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:0001080	Process	Nitrogen catabolite activation of transcription from RNA polymerase II promoter	IC	21757002
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	21757002, 24211198, 27471003
GO:0001678	Process	Cellular glucose homeostasis	IEA
GO:0003700	Function	DNA-binding transcription factor activity	TAS	9223286
GO:0004879	Function	Nuclear receptor activity	IBA	21873635
GO:0004879	Function	Nuclear receptor activity	IDA	23767959, 27471003
GO:0004879	Function	Nuclear receptor activity	ISS	21757002
GO:0005515	Function	Protein binding	IPI	12917342, 14684751, 14701856, 15317749, 19833092, 21532585, 22345554
GO:0005654	Component	Nucleoplasm	TAS
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IDA	10334992
GO:0006367	Process	Transcription initiation from RNA polymerase II promoter	TAS
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: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:0010988	Process	Regulation of low-density lipoprotein particle clearance	IDA	12660231
GO:0015721	Process	Bile acid and bile salt transport	TAS
GO:0016922	Function	Nuclear receptor binding	TAS	21757002
GO:0030154	Process	Cell differentiation	IBA	21873635
GO:0030522	Process	Intracellular receptor signaling pathway	ISS
GO:0032052	Function	Bile acid binding	IBA	21873635
GO:0032052	Function	Bile acid binding	ISS	21757002
GO:0032052	Function	Bile acid binding	TAS	21757002
GO:0032088	Process	Negative regulation of NF-kappaB transcription factor activity	IEA
GO:0032620	Process	Interleukin-17 production	IDA	21242261
GO:0032689	Process	Negative regulation of interferon-gamma production	IDA	21242261
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:0034142	Process	Toll-like receptor 4 signaling pathway	IDA	19864602
GO:0034162	Process	Toll-like receptor 9 signaling pathway	IEA
GO:0034255	Process	Regulation of urea metabolic process	ISS	21757002
GO:0034971	Process	Histone H3-R17 methylation	IDA	15471871
GO:0035356	Process	Cellular triglyceride homeostasis	IDA	20447400
GO:0035774	Process	Positive regulation of insulin secretion involved in cellular response to glucose stimulus	IEA
GO:0038181	Function	Bile acid receptor activity	IBA	21873635
GO:0038181	Function	Bile acid receptor activity	IDA	10334992
GO:0038181	Function	Bile acid receptor activity	TAS	23767959
GO:0038183	Process	Bile acid signaling pathway	IBA	21873635
GO:0038183	Process	Bile acid signaling pathway	ISS
GO:0038183	Process	Bile acid signaling pathway	TAS	23767959
GO:0038185	Process	Intracellular bile acid receptor signaling pathway	IDA	10334992
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 I-kappaB kinase/NF-kappaB signaling	IDA	21242261
GO:0043235	Component	Receptor complex	IDA	10334992
GO:0043565	Function	Sequence-specific DNA binding	IDA	12815072
GO:0045087	Process	Innate immune response	IEA
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	27471003
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA	21873635
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	23767959
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:0046965	Function	Retinoid X receptor binding	IEA
GO:0050728	Process	Negative regulation of inflammatory response	IBA	21873635
GO:0055089	Process	Fatty acid homeostasis	IEA
GO:0061178	Process	Regulation of insulin secretion involved in cellular response to glucose stimulus	IDA	20447400
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:0071417	Process	Cellular response to organonitrogen compound	ISS	21757002
GO:0071638	Process	Negative regulation of monocyte chemotactic protein-1 production	IEA
GO:0090181	Process	Regulation of cholesterol metabolic process	TAS	21757002
GO:1902122	Function	Chenodeoxycholic acid binding	IDA	10334992
GO:1903413	Process	Cellular response to bile acid	IDA	10334992
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	ISS	21757002
GO:2001250	Process	Positive regulation of ammonia assimilation cycle	IEA

Other IDs

• MIM: 603826
• HGNC: 7967
• e!Ensembl: ENSG00000012504

Protein

• UniProt ID: 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

• Sequence:

  MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAKGVLTEQVAGPLGQNLEVEPYSQYS
  NVQFPQVQPQISSSSYYSNLGFYPQQPEEWYSPGIYELRRMPAETLYQGETEVAEMPVTK
  KPRMGASAGRIKGDELCVVCGDRASGYHYNALTCEGCKGFFRRSITKNAVYKCKNGGNCV
  MDMYMRRKCQECRLRKCKEMGMLAECMYTGLLTEIQCKSKRLRKNVKQHADQTVNEDSEG
  RDLRQVTSTTKSCREKTELTPDQQTLLHFIMDSYNKQRMPQEITNKILKEEFSAEENFLI
  LTEMATNHVQVLVEFTKKLPGFQTLDHEDQIALLKGSAVEAMFLRSAEIFNKKLPSGHSD
  LLEERIRNSGISDEYITPMFSFYKSIGELKMTQEEYALLTAIVILSPDRQYIKDREAVEK
  LQEPLLDVLQKLCKIHQPENPQHFACLLGRLTELRTFNHHHAEMLMSWRVNDHKFTPLLC
  EIWDVQ

• Sequence length: 486

Pathways

KEGG:

Bile secretion

Reactome:

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

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Cholestasis	Cholestasis	rs121909103, rs751511532, rs376368459, rs762702807, rs1578490102, rs1578499691, rs1578504946, rs1317656688, rs199791850, rs1452792080, rs1578491039	23178280, 22461449
Cholestasis of pregnancy	Cholestasis of pregnancy	rs11568372, rs121918440, rs387906527, rs72552778, rs387906528, rs72552780, rs769910565, rs188824058, rs375315619, rs754287486, rs764513998, rs759202962, rs377160065, rs1562965036, rs764296800, rs1584665400, rs1584671714, rs1187517509, rs1584684209, rs533310204, rs571555115, rs1584754706, rs1584754766, rs1584763429, rs757693457, rs1574445178, rs1584742063, rs1584750660, rs752563752	23142591
Intrahepatic cholestasis	Progressive intrahepatic cholestasis (disorder), CHOLESTASIS, PROGRESSIVE FAMILIAL INTRAHEPATIC, 5, Progressive familial intrahepatic cholestasis type 5	rs121918299, rs80338722, rs80338725, rs80338719, rs80338723, rs80338726, rs72549401, rs11568372, rs1553469602, rs387907317, rs387906354, rs752919965, rs72549397, rs111033609, rs121909099, rs387906381, rs121909100, rs121909101, rs121909104, rs121909105, rs387906526, rs121918440, rs387906527, rs72552778, rs387906529, rs121918443, rs72552780, rs80338724, rs80338715, rs80338727, rs80338729, rs80338716, rs80338717, rs398122839, rs515726137, rs587777519, rs587777520, rs587777521, rs879255644, rs113090017, rs864321695, rs776869985, rs864321697, rs80338720, rs746155190, rs879255504, rs886041948, rs886042562, rs769910565, rs758069019, rs886043807, rs72549402, rs72549395, rs188824058, rs763782349, rs375315619, rs754287486, rs1057518679, rs1060499649, rs1060499579, rs1554660803, rs1554407511, rs774824767, rs771690686, rs752992432, rs1553466082, rs72549396, rs772294884, rs764513998, rs1202682161, rs759202962, rs1562774655, rs1562831765, rs1562945221, rs917981474, rs1558927163, rs765889649, rs1562976061, rs72549399, rs1459273753, rs377160065, rs1559183717, rs760750012, rs1051861187, rs1558898789, rs928915940, rs752757689, rs1584678508, rs764581483, rs1574453508, rs751511532, rs1182781290, rs376368459, rs762702807, rs1578499691, rs199791850, rs1452792080, rs1458423947, rs1584747270, rs1584750653, rs1599066459, rs1599069873, rs1599166106, rs1574462504, rs1593114820, rs1057524081, rs1588081022, rs777460754, rs1251192873, rs1588117076, rs748671901, rs139314808, rs749009273, rs1588080674, rs1588080680, rs1588127136, rs1588135086, rs757693457, rs1574445178, rs768922690, rs1584422832, rs1584433525, rs1312396424, rs1792048079, rs774411820, rs575729461	21633855, 26888176, 26888176
Liver failure	Liver Failure	rs118203990, rs118203991, rs118203992, rs387907022, rs201861847, rs796065037, rs759315662, rs368196005, rs796052121, rs369437593, rs367683258, rs766314948, rs368085185, rs770446752, rs753039116, rs776797592, rs1490906786, rs1562849964, rs759960319, rs776597537, rs375350359, rs1573008071, rs1601977105, rs1174791046, rs1019313682

Unknown
Disease name	Disease term	dbSNP ID	References
Atherosclerosis	Atherosclerosis	rs699947, rs59439148	30996006
Ciliopathies	Ciliopathies
Cirrhosis	Cirrhosis	rs119465999, rs144369314, rs8056684, rs112053857, rs75998507
Crohn disease	Crohn Disease, Regional enteritis	rs2066847, rs2066844, rs886052047, rs5743265, rs111608429, rs104895438	21829567
Crohn`s disease of large bowel	Crohn`s disease of large bowel		21829567
Crohn`s disease of the ileum	Crohn`s disease of the ileum		21829567
Fatty liver	Fatty Liver, Steatohepatitis		29142166
Fibroatheroma	Fibroatheroma		30996006
Hypoglycemia	Hypoglycemia
Ileocolitis	IIeocolitis		21829567
Intestinal neoplasms	Intestinal Neoplasms		23178280
Intestinal cancer	Intestinal Cancer		23178280
Intrahepatic cholestasis of pregnancy	Intrahepatic cholestasis of pregnancy
Liver neoplasms	Liver neoplasms		30556042, 24189133, 29142166, 23178280, 24091600
Liver cancer	Malignant neoplasm of liver		30556042, 29142166, 24189133, 23178280, 24091600
Liver carcinoma	Liver carcinoma		23811326, 25496033
Non-alcoholic fatty liver disease	Non-alcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis		29142166