NR1H4
Bile acid receptor
Also known as: FXR, HRR-1, HRR1, NR1H4_HUMAN, RIP14
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q96RI1
- Gene
- NR1H4
- Ensembl
- ENSG00000012504
- Chromosome
- 12
- Canonical length
- 486 aa
- Protein class
- Disease related genes, FDA approved drug targets, Human disease related genes, Nuclear receptors, Predicted intracellular proteins, Transcription factors, Transporters
- Subcellular location
- Nucleoplasm,Nuclear speckles,Primary cilium tip,Cytosol
OverviewNCBI Gene
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 the expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Feb 2016]
Canonical amino-acid sequenceUniProt
486 residues, UniProt reviewed canonical sequence.
>Q96RI1|NR1H4
1 MVMQFQGLEN PIQISPHCSC TPSGFFMEMM SMKPAKGVLT EQVAGPLGQN LEVEPYSQYS
61 NVQFPQVQPQ ISSSSYYSNL GFYPQQPEEW YSPGIYELRR MPAETLYQGE TEVAEMPVTK
121 KPRMGASAGR IKGDELCVVC GDRASGYHYN ALTCEGCKGF FRRSITKNAV YKCKNGGNCV
181 MDMYMRRKCQ ECRLRKCKEM GMLAECMYTG LLTEIQCKSK RLRKNVKQHA DQTVNEDSEG
241 RDLRQVTSTT KSCREKTELT PDQQTLLHFI MDSYNKQRMP QEITNKILKE EFSAEENFLI
301 LTEMATNHVQ VLVEFTKKLP GFQTLDHEDQ IALLKGSAVE AMFLRSAEIF NKKLPSGHSD
361 LLEERIRNSG ISDEYITPMF SFYKSIGELK MTQEEYALLT AIVILSPDRQ YIKDREAVEK
421 LQEPLLDVLQ KLCKIHQPEN PQHFACLLGR LTELRTFNHH HAEMLMSWRV NDHKFTPLLC
481 EIWDVQLocalizationUniProt · AlphaFold · HPA
Whether an antibody against NR1H4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.43
- Highest tissue expression
- 113 nTPM
Expression across tissuesHPA
Tissue
- liver: 113 nTPM
- small intestine: 37 nTPM
- duodenum: 28 nTPM
- kidney: 26 nTPM
- adrenal gland: 21 nTPM
- ovary: 14 nTPM
Single-cell type
- enterocytes: 674 nCPM
- hepatocytes: 256 nCPM
- cholangiocytes: 212 nCPM
- adrenal cortex cells: 212 nCPM
- proximal tubule cells: 175 nCPM
- hepatic stellate cells: 155 nCPM
Immune cell
- memory B-cell: 0.1 nTPM
- neutrophil: 0.1 nTPM
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
Brain region
- choroid plexus: 5.7 nTPM
- white matter: 3 nTPM
- cerebellum: 2.8 nTPM
- cerebral cortex: 2.7 nTPM
- hypothalamus: 2.5 nTPM
- hippocampal formation: 2.4 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about NR1H4.
Disease | AllUniProt
Conditions NR1H4 is implicated in, by any mechanism.
- Cholestasis, progressive familial intrahepatic, 5 (PFIC5) MIM:617049
Disease | GeneticClinVar
16 pathogenic / likely-pathogenic of 164 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Cholestasis, progressive familial intrahepatic, 5
- Progressive familial intrahepatic cholestasis type 1
- NR1H4-related disorder
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.63
- gnomAD pLI
- 0
- gnomAD missense Z
- 1.54
- DepMap mean gene effect
- -0.09
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- bile acid and bile salt transport
- bile acid metabolic process
- cell differentiation
- cell-cell junction assembly
- cellular response to bile acid
- cellular response to fatty acid
- cellular response to lipopolysaccharide
- cholesterol homeostasis
- defense response to bacterium
- fatty acid homeostasis
- inflammatory response
- innate immune response
- intracellular glucose homeostasis
- intracellular receptor signaling pathway
- intracellular triglyceride homeostasis
- negative regulation of apoptotic process
- negative regulation of canonical NF-kappaB signal transduction
- negative regulation of inflammatory response
- negative regulation of interleukin-1 production
- negative regulation of interleukin-2 production
- negative regulation of interleukin-6 production
- negative regulation of monocyte chemotactic protein-1 production
- negative regulation of transcription by RNA polymerase II
- negative regulation of tumor necrosis factor production
- negative regulation of tumor necrosis factor-mediated signaling pathway
- negative regulation of type II interferon production
- negative regulation of very-low-density lipoprotein particle remodeling
- Notch signaling pathway
- nuclear receptor-mediated bile acid signaling pathway
- positive regulation of adipose tissue development
- positive regulation of DNA-templated transcription
- positive regulation of insulin receptor signaling pathway
- positive regulation of insulin secretion involved in cellular response to glucose stimulus
- positive regulation of interleukin-17 production
- positive regulation of transcription by RNA polymerase II
- regulation of bile acid biosynthetic process
- regulation of cholesterol metabolic process
- regulation of DNA-templated transcription
- regulation of insulin secretion involved in cellular response to glucose stimulus
- regulation of low-density lipoprotein particle clearance
- regulation of transcription by RNA polymerase II
- toll-like receptor 9 signaling pathway
- transcription by RNA polymerase II
- positive regulation of ammonia assimilation cycle
- positive regulation of glutamate metabolic process
- positive regulation of phosphatidic acid biosynthetic process
- regulation of urea metabolic process
Molecular functions
- bile acid binding
- bile acid nuclear receptor activity
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- nuclear receptor activity
- nuclear receptor binding
- nuclear retinoid X receptor binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- RNA polymerase II transcription regulatory region sequence-specific DNA binding
- sequence-specific DNA binding
- transcription cis-regulatory region binding
- transcription coregulator binding
- zinc ion binding
- chenodeoxycholic acid binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Nuclear hormone receptor, ligand-binding domain
- Zinc finger, nuclear hormone receptor-type
- Nuclear hormone receptor
- Thyroid hormone receptor
- Zinc finger, NHR/GATA-type
- Nuclear hormone receptor-like domain superfamily
- Nuclear hormone receptor family NR1 subfamily
- Ligand-binding domain of nuclear hormone receptor
- Double treble clef zinc finger, C4 type
- Bile acid receptor, ligand binding domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of NR1H4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads NR1H4 as an antibody target. Whether an autoantibody or antibody against NR1H4 could matter depends on whether native NR1H4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
NR1H4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label NR1H4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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