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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

NR1H4 Gene

protein-coding GIFtS: 67
GCID: GC12P100850

nuclear receptor subfamily 1, group H, member 4

Explore 56 diseases affiliated with
NR1H4 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Nuclear Receptor Subfamily 1, Group H, Member 4¹ ²		Retinoid X Receptor-Interacting Protein 14² ³
FXR¹ ² ³ ⁵		BAR² ³
RIP14¹ ² ³ ⁵		RXR-Interacting Protein 14² ³
HRR1¹ ² ³		Bile Acid Receptor²
HRR-1¹ ²		Farnesoid X Nuclear Receptor²
Farnesoid X-Activated Receptor² ³		Nuclear Receptor Subfamily 1 Group H Member 4³
Farnesol Receptor HRR-1² ³

External Ids:	HGNC: 7967¹	Entrez Gene: 9971²	Ensembl: ENSG00000012504⁷	OMIM: 603826⁵	UniProtKB: Q96RI1³

Export aliases for NR1H4 gene to outside databases

Previous GC identifers: GC12P100078 GC12P099370 GC12P097928

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for NR1H4:

This gene encodes a ligand-activated transcription factor, which shares structural features in common with nuclear

hormone receptor family, such as a DNA-binding domain that targets the receptor to specific DNA sequences, and a

ligand-binding domain, which interacts directly with the ligand and contains a ligand-dependent transcriptional

activation domain. This protein functions as a receptor for bile acids, and when bound to bile acids, regulates the

expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants encoding

different isoforms have been described for this gene. (provided by RefSeq, Aug 2011)

UniProtKB/Swiss-Prot: NR1H4_HUMAN, Q96RI1

Function: Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic

acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through

the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding

protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone

methyltransferase CARM1 to this locus

summary for NR1H4:

Liver X receptors (LXRs) and farnesoid X receptors (FXRs) are members of the steroid analog-activated

nuclear receptor subfamily, which form heterodimers with members of the retinoid X receptor family. There

are two closely related isoforms of each of these enzymes; LXRalpha and LXRbeta, and FXRalpha and FXRbeta

(pseudogene in man). LXRalpha and FXRalpha expression is restricted to the liver, small intestine, kidney

and adrenal gland, whilst LXRbeta and FXRbeta are ubiquitously expressed. Despite acting on some of the same

target genes, including cholesterol 7alpha-hydroxylase (CYP7A1) and SREBP-1c, LXRs and FXRs have different

physiological roles. LXRs are involved in cholesterol homeostasis, inhibition of proinflammatory gene

expression in atherosclerosis and activation of innate immunity, whilst FXRs have a vital function in bile

acid homeostasis.

Gene Wiki entry for NR1H4 (Farnesoid X receptor)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000012.11 NC_018923.1 NT_029419.12

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the NR1H4 gene promoter:
NF-1 MEF-2 Evi-1 HNF-4alpha1 MEF-2A PPAR-gamma1 Chx10 PPAR-gamma2 aMEF-2 RSRFC4
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): NR1H4 promoter sequence

Search SABiosciences Chromatin IP Primers for NR1H4

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat NR1H4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 12q23.1 Ensembl cytogenetic band: 12q23.1 HGNC cytogenetic band: 12q23.1

NR1H4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NR1H4 gene location

GeneLoc information about chromosome 12 GeneLoc Exon Structure

GeneLoc location for GC12P100850: view genomic region (about GC identifiers)

Start:	100,867,486 bp from pter	End:	100,958,191 bp from pter
Size:	90,706 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: NR1H4_HUMAN, Q96RI1 (See protein sequence)

Recommended Name: Bile acid receptor

Size: 486 amino acids; 55914 Da

Subunit: Heterodimer of NR1H4 and RXR. After activation by agonist binding, interacts with a coactivator, NCOA1 or

NCOA2 (By similarity). Interacts with CARM1 and SMARD1

Subcellular location: Nucleus (Probable)

Sequence caution: Sequence=BC144183; Type=Frameshift; Positions=156;

6/23 PDB 3D structures from and Proteopedia for NR1H4 (see all 23):

1OSH (3D)

1OSK (3D)

3BEJ (3D)

3DCT (3D)

3DCU (3D)

3FLI (3D)

Secondary accessions: A1L4K5 B7Z412 B7ZM06 F8VYG8 Q8NFP5 Q8NFP6 Q92943

Alternative splicing: 5 isoforms: Q96RI1-3 Q96RI1-4 Q96RI1-1 Q96RI1-2 Q96RI1-5 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for NR1H4: NX_Q96RI1

Post-translational modifications:

Methylation may increase transactivation of target genes¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q96RI1

NR1H4 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (6 alternative transcripts):

NP_001193906.1 NP_001193907.1 NP_001193908.1 NP_001193921.1 NP_001193922.1 NP_005114.1

ENSEMBL proteins:

ENSP00000448506 ENSP00000376712 ENSP00000315442 ENSP00000448978 ENSP00000446760

ENSP00000446584 ENSP00000447149 ENSP00000188403 ENSP00000446861

Reactome Protein details: Q96RI1
Human Recombinant Protein Products:

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	Browse ProSpec Recombinant Proteins
	Uscn Proteins for NR1H4

Gene Ontology (GO): 3 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	--	--
GO:0005654	nucleoplasm	TAS	--
GO:0005719	nuclear euchromatin	IDA	--

NR1H4 for ontologies About GeneDecksing

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	Novus Biologicals NR1H4 Antibodies
	Abcam antibodies for NR1H4
	Uscn Antibodies for NR1H4
	ThermoFisher Antibodies for NR1H4

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	GenScript Custom Assay Services for NR1H4
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for NR1H4

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

NR1H4 for domains About GeneDecksing

5/6 InterPro domains/families (see all 6):

IPR013088 Znf_NHR/GATA

IPR008946 Nucl_hormone_rcpt_ligand-bd

IPR000536 Nucl_hrmn_rcpt_lig-bd_core

IPR001628 Znf_hrmn_rcpt

IPR001723 Str_hrmn_rcpt

Graphical View of Domain Structure for InterPro Entry Q96RI1

ProtoNet protein and cluster: Q96RI1

2 Blocks protein families:

IPB000324 Vitamin D receptor signature

IPB001723 Steroid hormone receptor signature

UniProtKB/Swiss-Prot: NR1H4_HUMAN, Q96RI1

Similarity: Belongs to the nuclear hormone receptor family. NR1 subfamily

Similarity: Contains 1 nuclear receptor DNA-binding domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: NR1H4_HUMAN, Q96RI1

Function: Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic

acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through

the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding

protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone

methyltransferase CARM1 to this locus

miRNA Products:		OriGene 3'-UTR Clone: NR1H4 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat NR1H4
		1 QIAGEN miScript miRNA Assays for microRNA that regulate NR1H4:
		hsa-miR-582-5p
		SwitchGear 3'UTR luciferase reporter plasmid: NR1H4 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
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		GenScript: all cDNA clones in your preferred vector: NR1H4 (NM_005123)
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		Search LifeMap BioReagents cell lines for NR1H4

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NR1H4

Gene Ontology (GO): 5/20 molecular function terms (GO ID links to tree view) (see all 20): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000980	RNA polymerase II distal enhancer sequence-specific DNA binding	IDA	--
GO:0001190	RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription	IDA	--
GO:0003677	DNA binding	--	--
GO:0003690	double-stranded DNA binding	--	--
GO:0003700	sequence-specific DNA binding transcription factor activity	TAS	9223286

NR1H4 for ontologies About GeneDecksing

2 GenomeRNAi human phenotypes for NR1H4:

Downregulation of NF-kappaB pa

Animal Models:
Mouse knock-outs for NR1H4: Nr1h4^tm1.2Auw Nr1h4^tm1Kok Nr1h4^tm1Gonz
8 MGI mutant phenotypes (inferred from 6 alleles) (MGI details for Nr1h4):

cellular	growth/size	homeostasis/metabolism	immune system	liver/biliary system
mortality/aging	no phenotypic analysis	tumorigenesis

NR1H4 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/7 super-pathways (see all 7) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Generic Transcription Pathway

Generic Transcription Pathway

1.00

Gene Expression

0.46

Nuclear Receptor transcription pathway

Nuclear Receptor transcription pathway

1.00

Selected targets of HNF1

Selected targets of HNF1

1.00

Drug Induction of Bile Acid Pathway

Drug Induction of Bile Acid Pathway

1.00

Nuclear receptors in lipid metabolism and toxicity

Nuclear receptors in lipid metabolism and toxicity

1.00

Pathway sources
See GeneCards unified pathways
Show all pathways

1 EMD Millipore Pathway for NR1H4

Selected targets of HNF1

3 BioSystems Pathways for NR1H4

	Nuclear receptors in lipid metabolism and toxicity
	Drug Induction of Bile Acid Pathway
	RXR and RAR heterodimerization with other nuclear receptor

3 Reactome Pathways for NR1H4

	Generic Transcription Pathway
	Nuclear Receptor transcription pathway
	Gene Expression

1 Kegg Pathway (Kegg details for NR1H4):

Bile secretion

NR1H4 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for NR1H4

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/52 Interacting proteins for NR1H4 (Q96RI1³ ENSP00000315442⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 52)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
HIST1H4A	P62805³, ENSP00000352980⁴	I2D: score=1 STRING: ENSP00000352980
HIST1H4B	P62805³	I2D: score=1
HIST1H4C	P62805³	I2D: score=1
HIST1H4D	P62805³	I2D: score=1
HIST1H4E	P62805³	I2D: score=1

About this table

Gene Ontology (GO): 5/23 biological process terms (GO ID links to tree view) (see all 23): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	ISS	--
GO:0001080	nitrogen catabolite activation of transcription from RNA polymerase II promoter	IC	--
GO:0006109	regulation of carbohydrate metabolic process	IEA	--
GO:0006351	transcription, DNA-dependent	--	--
GO:0006355	regulation of transcription, DNA-dependent	--	--

NR1H4 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

NR1H4 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Enzo Life Sciences drugs & compounds for NR1H4

Compounds for NR1H4 available from Tocris Bioscience About this table

Compound	Action	CAS #
GW 4064	Selective farnesoid X receptor (FXR) agonist	[278779-30-9]
Fexaramine	Potent, selective farnesoid X receptor (FXR) agonist	[574013-66-4]

2 HMDB Compounds for NR1H4 About this table

Compound	Synonyms	CAS #	PubMed Ids
Deoxycholic acid	5b-Cholanic acid-3a,12a-diol (see all 14)	83-44-3	--
Lithocholic acid	(3a,5b)-3-hydroxy-cholan-24-oate (see all 5)	434-13-9	--

3 DrugBank Compounds for NR1H4 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Chenodeoxycholic acid	Chenocholic acid (see all 3)	474-25-9	target	other	10334992 20104269
Fexaramine	--	574013-66-4	target	--	17139284 17016423
(8alpha,10alpha,13alpha,17beta)-17-[(4-hydroxyphenyl)carbonyl]androsta-3,5-diene-3-carboxylic acid	--	--	target	--	10592235

10/43 Novoseek chemical compound relationships for NR1H4 gene (see all 43) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
gw 4064	97.3	55	12052824 (3), 15882126 (2), 19228886 (2), 11607932 (2) (see all 33)
chenodeoxycholic acid	94	111	19913492 (3), 17975826 (2), 16522742 (2), 19059462 (2) (see all 55)
guggulsterone	92.3	38	17135343 (4), 12705905 (3), 17054793 (2), 18519703 (2) (see all 17)
6-ethylchenodeoxycholic acid	89.6	12	15317466 (1), 18029909 (1), 19864602 (1), 19418582 (1) (see all 5)
androstane	88.6	39	19300246 (2), 17132852 (1), 18037906 (1), 20048746 (1) (see all 24)
guggul	85.5	3	16428513 (1), 19102680 (1)
lithocholic acid	81.6	21	12052824 (5), 16178789 (2), 16946559 (1), 10334993 (1) (see all 7)
cholesterol	75.2	199	19136377 (4), 12704471 (4), 15558057 (3), 15962294 (3) (see all 94)
apomine	73.5	1	11350890 (1)
farnesol	67.1	16	10753967 (1), 17333335 (1), 8625436 (1), 16540091 (1) (see all 9)

Search CenterWatch for drugs/clinical trials and news about NR1H4

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for NR1H4 gene (6 alternative transcripts):

NM_001206977.1 NM_001206978.1 NM_001206979.1 NM_001206992.1 NM_001206993.1 NM_005123.3

Unigene Cluster for NR1H4:

Nuclear receptor subfamily 1, group H, member 4

Hs.282735 [show with all ESTs]

Unigene Representative Sequence: NM_001206977

9 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000548884(uc001thq.2 uc001thp.2 uc001thr.2 uc010svk.2 uc010svj.2 uc001ths.2 uc001tht.2)

ENST00000392986 ENST00000321046 ENST00000549996 ENST00000546380 ENST00000548621

ENST00000551379 ENST00000188403 ENST00000551184

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		1 QIAGEN miScript miRNA Assays for microRNA that regulate NR1H4:
		hsa-miR-582-5p
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		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat NR1H4

Additional cDNA sequence:

AB307699.1 AF384555.1 AF478445.1 AF478446.1 AK296612.1 AK296647.1 AK312959.1 BC035654.1

BC071778.1 BC130573.1 BC144183.1 BC144184.1 BC144187.1 BX571749.1 HQ709175.1 U68233.1

6 DOTS entries:

DT.213616 DT.100021403 DT.100746912 DT.40229020 DT.444293 DT.402350

24/60 AceView cDNA sequences (see all 60):

AF478445 BX102734 AI051958 BC071778 AU104249 AI075131 BX571749 BC035654

AA912967 AI628645 AF384555 AI245366 AF478446 CB162215 AA682292 BX092610

R92996 T89438 AA862482 NM_005123 AI809578 BG171220 U68233 H79617

GeneLoc Exon Structure

5/7 Alternative Splicing Database (ASD) splice patterns (SP) for NR1H4 (see all 7) About this scheme

ExUns:	1a	·	1b	·	1c	·	1d	^	2	^	3	^	4a	·	4b	·	4c	·	4d	^	5	^	6	^	7	^	8a	·	8b	^	9	^	10	^	11	^	12	^	13	^	14a	·	14b
SP1:									-				-								-		-						-
SP2:																					-		-
SP3:																							-						-
SP4:																							-
SP5:

ECgene alternative splicing isoforms for NR1H4

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

NR1H4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: --

About this image

NR1H4 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

4 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Kidney

Proximal Tubule

Proximal Tubule Cells

Kidney

Ovary

Kidney

Kidney

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 1 LifeMap Cell

Name

Category

HyStem+BMP4-induced 7SMOO32 cells (HyStem+BMP4 inductio...)

Adipose

See NR1H4 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for NR1H4

SOURCE GeneReport for Unigene cluster: Hs.282735

SABiosciences Expression via Pathway-Focused PCR Arrays including NR1H4:

Lipoprotein Signaling & Cholesterol Metabolism in human mouse rat

Nuclear Receptors & Coregulators in human mouse rat

Fatty Liver in human mouse rat

Molecular Toxicology PathwayFinder 384HT in human mouse rat

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In Situ
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Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NR1H4

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for NR1H4 gene from 6/19 species (see all 19) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	NR1H4¹	nuclear receptor subfamily 1, group H, member 4	77.9(n) 82.47(a)		373902 NM_204113.1 NP_989444.1
lizard (Anolis carolinensis)	Reptilia	NR1H4⁶	--	74(a)	1 ↔ 1	5(28595826-28625495)
African clawed frog (Xenopus laevis)	Amphibia	MGC68693²	hypothetical protein MGC68693	73.44(n)		AF456451.1
zebrafish (Danio rerio)	Actinopterygii	nr1h4¹	nuclear receptor subfamily 1, group H, member 4	66.59(n) 68.02(a)		436847 NM_001002574.1 NP_001002574.1
fruit fly (Drosophila melanogaster)	Insecta	EcR³	imaginal disc eversion ecdysteroid hormone receptor	36(a)		--
worm (Caenorhabditis elegans)	Secernentea	nhr-48⁶ nhr-8⁶ (see all 3)	Nuclear hormone receptor family member nhr-8 (see all 3)	8(a) 14(a) (see all 3)	possible ortholog possible ortholog (see all 3)	X(15708153-15716345) IV(7710977-7714670)

ENSEMBL Gene Tree for NR1H4 (if available)
TreeFam Gene Tree for NR1H4 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for NR1H4 gene

VDR² NR4A3² NR4A1² NR1I2² RARG² NR1I3² THRB² RARA²

NR1H2² NR4A2² RARB² THRA² NR1H3²

11 SIMAP similar genes for NR1H4 using alignment to 8 protein entries: NR1H4_HUMAN (see all proteins):

DKFZp686P04237 HNF4G VDR NR1H3 NR1I3 NR1H2

NR1B2 NR1I2 DKFZp686D1580 NR1i1 RARB

NR1H4 for paralogs About GeneDecksing

1 Pseudogenes.org Pseudogene for NR1H4
PGOHUM00000261311

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
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SNP ID	Valid	Clinical significance	Chr 12 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs80312960^1,2		--	97926640(+)	`CAGTAC/TAGGCT`	4	--	us2k¹		0	--	--	--	--
rs2864058^1,2	H	--	97926969(-)	`TGTGGT/CCATTT`	4	--	us2k¹		3		EA NS	296
rs11110388^1,2	C,H	--	97927065(+)	`GGGAAG/ATTGTT`	4	--	us2k¹		4		NS EA	408
rs17030186^1,2	C,F,H,	--	97927111(+)	`TACACA/GATGCT`	4	--	us2k¹ tfbs³		10		NA NS WA	1162
rs3863377^1,2	C,F,A,H,	--	97927423(-)	`TCTCCC/TGCCTC`	4	--	us2k¹		4		NS NA	222
rs75017508^1,2	F,	--	97927962(+)	`CTATGA/GTAGGC`	4	--	us2k¹		1		WA	118
rs28541374^1,2	C,F,H,	--	97928237(+)	`CTTTCA/GAAGGC`	4	--	us2k¹ tfbs³		11		NS NA WA	1192
rs56276483^1,2	C,F,	--	97928527(+)	`TGAGCA/CTTTGT`	4	--	ut5¹		1		NA	120
rs75762522^1,2	C,	--	97928678(+)	`AAAAAT/CAGTCA`	4	--	int¹		2		WA	120
rs78243656^1,2	C,F,	--	97928936(+)	`ATTCCA/GTNNNN`	4	--	int¹		1		NA	120

HapMap Linkage Disequilibrium report for NR1H4 (100867486 - 100958191 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 1 variation for NR1H4
1 CNV: 38276
Human Gene Mutation Database (HGMD): NR1H4

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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NR1H4 for disorders           About GeneDecksing

OMIM gene information: 603826    OMIM disorders: --

20/56 diseases for NR1H4 (see all 56):    About MalaCards

bile acid malabsorption atherosclerosis fragile x syndrome cerebrotendinous xanthomatosis

maturity-onset diabetes of the young cholesterol intrahepatic cholestasis xanthomatosis

biliary atresia familial combined hyperlipidemia nonalcoholic steatohepatitis cholestasis

type 2 diabetes mellitus intrahepatic cholestasis of pregnancy primary biliary cirrhosis biliary tract disease

barrett's esophagus insulin resistance metabolic disorders fatty liver disease

3 diseases from the University of Copenhagen DISEASES database for NR1H4:

Cholestasis Liver disease Atherosclerosis

10/28 Novoseek disease relationships for NR1H4 gene (see all 28) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
byler disease	80.9	14	19381753 (4), 16628629 (2), 19027009 (1), 16819395 (1)
cholestasis	76.7	29	19027009 (2), 19300246 (2), 15317749 (2), 16178789 (2) (see all 12)
cholestasis intrahepatic	73.5	15	14988830 (2), 17681172 (1), 16819395 (1), 19490418 (1) (see all 8)
dyslipidemia	54.8	10	19136377 (2), 15893927 (1), 18047847 (1), 18311660 (1)
liver diseases	50.4	8	19187229 (1), 18668687 (1), 14992012 (1), 16706681 (1) (see all 6)
biliary cirrhosis primary	48.6	2	15703646 (1), 19300246 (1)
fragile x syndrome	45.9	2	8668200 (2)
hypercholesterolemia	44	15	18948497 (2), 19136377 (1), 12704471 (1), 16905319 (1)
atherosclerosis	39.6	8	20041971 (2), 17495603 (2), 17519356 (1), 18311660 (1) (see all 6)
biliary atresia	39.4	2	16628629 (1), 15922475 (1)

Human Genome Epidemiology (HuGE) Navigator: NR1H4 (13 documents)

Export disorders for NR1H4 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for NR1H4 gene, integrated from 9 sources (see all 447):
(articles sorted by number of sources associating them with NR1H4)

Utopia: connect your pdf to the dynamic
world of online information

Identification of a nuclear receptor for bile acids. (PubMed id 10334992)^{1, 2, 7, 9} Makishima M.... Shan B. (1999)
Ligand-dependent activation of the farnesoid X-receptor directs arginine methylation of histone H3 by CARM1. (PubMed id 15471871)^{1, 2, 9} Ananthanarayanan M....Walsh M.J. (2004)
Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. (PubMed id 12815072)^{1, 2, 9} Holt J.A....Jones S.A. (2003)
Bile acids: natural ligands for an orphan nuclear receptor. (PubMed id 10334993)^{1, 2, 9} Parks D.J....Lehmann J.M. (1999)
BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation. (PubMed id 12917342)^{1, 2} Hsiao P.W.... Archer T.K. (2003)
Generation of multiple farnesoid-X-receptor isoforms through the use of alternative promoters. (PubMed id 12062799)^{1, 2} Huber R.M.... Burn T.C. (2002)
Activation of the orphan receptor RIP14 by retinoids. (PubMed id 9223286)^{1, 3} Zavacki A.M....Moore D.D. (1997)
Identification of a nuclear receptor that is activated by farnesol metabolites. (PubMed id 7774010)^{1, 3} Forman B.M....Weinberger C. (1995)
Knockdown of ATP8B1 expression leads to specific downregulation of the bile acid sensor FXR in HepG2 cells: effect of the FXR agonist GW4064. (PubMed id 19228886)^{1, 9} MartA-nez-FernA!ndez P....Alvarez L. (2009)
[Effects of farnesoid X receptor on lipid metabolism in L02 cells] (PubMed id 19105941)^{1, 9} Hong J.L....Bai M.J. (2008)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 9971	HGNC: 7967	AceView: NR1H4	Ensembl:ENSG00000012504	euGenes: HUgn9971
ECgene: NR1H4	Kegg: 9971	H-InvDB: NR1H4

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for NR1H4	Pharmacogenomics, SNPs, Pathways
Wikipedia	http://en.wikipedia.org/wiki/Farnesoid_X_receptor

Intellectual Property for NR1H4 gene
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Patent Information for NR1H4 gene:
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GeneCards and IP:
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nuclear receptor subfamily 1, group H, member 4

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Dyslipidemia
Response Acute Phase
Insulin Resistance
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Hypertriglyceridemia
OBESITY
Cholestasis Intrahepatic
Hyperlipidemia
Osteoarthritis
insulin sensitivity
Liver diseases
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Breast Cancer
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Fragile X Syndrome
Hypercholesterolemia
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NR1H4 Gene

nuclear receptor subfamily 1, group H, member 4

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