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NR1H4
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  • NR1H4
PROTEIN SUMMARY SECTION OVERVIEW RNA DATA ANTIBODY DATA
Amygdala Basal ganglia Thalamus Midbrain Pons Medulla oblongata Hippocampal formation Spinal cord White matter Cerebral cortex Cerebellum Choroid plexus Hypothalamus Retina Thyroid gland Parathyroid gland Adrenal gland Pituitary gland Lung Salivary gland Esophagus Tongue Stomach Rectum Colon Duodenum Small intestine Liver Gallbladder Pancreas Kidney Urinary bladder Testis Epididymis Prostate Seminal vesicle Vagina Breast Cervix Endometrium Fallopian tube Ovary Placenta Heart muscle Skeletal muscle Smooth muscle Adipose tissue Skin Bone marrow Thymus Tonsil Lymph node Spleen Appendix
NR1H4 INFORMATION
Proteini

Full gene name according to HGNC.

Nuclear receptor subfamily 1 group H member 4
Gene namei

Official gene symbol, which is typically a short form of the gene name, according to HGNC.

NR1H4 (FXR, HRR-1, HRR1, RIP14)
Protein classi

Assigned HPA protein class(es) for the encoded protein(s).

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Disease related genes
FDA approved drug targets
Human disease related genes
Nuclear receptors
Transcription factors
Transporters
Number of transcriptsi

Number of protein-coding transcripts from the gene as defined by Ensembl.

9
Protein evidence Evidence at protein level (all genes)
PROTEIN EXPRESSION AND LOCALIZATION
Tissue profilei

A summary of the overall protein expression profile across the analyzed normal tissues based on knowledge-based annotation, presented in the Tissue section.

"Estimation of protein expression could not be performed. View primary data." is shown for genes where available RNA-seq and gene/protein characterization data in combination with immunohistochemistry data has been evaluated as not sufficient to yield a reliable estimation of the protein expression profile.
Not available
Subcellular location Localized to the Nucleoplasm
Predicted locationi

All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.

  • Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.

  • Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).

The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.

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Intracellular
TISSUE RNA EXPRESSION
Tissue specificityi

The RNA specificity category is based on normalized mRNA expression levels in the consensus dataset, calculated from the RNA expression levels in samples from HPA and GTEX. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected.

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Tissue enhanced (intestine, liver)
Tissue expression clusteri

The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Read more
Liver - Metabolism (mainly)
Brain specificityi

The regional specificity category is based on mRNA expression levels in the analysed brain samples, grouped into 13 main brain regions and calculated for the three different species. All brain expression profiles are based on data from HPA. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category

Read more
Not detected in human brain
Single cell type specificityi

The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.

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Group enriched (Proximal enterocytes, Proximal tubular cells, Hepatocytes, Cholangiocytes)
Single cell type
expression clusteri

The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Read more
Proximal enterocytes - Transmembrane transport (mainly)
Tissue cell type classificationi

Genes can have enriched specificity in different cell types in one or several tissues, or be enriched in a core cell type that appears in many different tissues.

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No predicted cell type specificity
IMMUNE CELLS
Immune cell specificityi

The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.

Read more
Not detected in immune cells
Immune cell
expression clusteri

The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Read more
Not detected - no cluster assigned
CANCER & CELL LINES
Prognostic summary Gene product is not prognostic
Cancer specificityi

Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected.

Read more
Group enriched (liver cancer, renal cancer)
Cell line
expression clusteri

The RNA data was used to cluster genes according to their expression across cell lines. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Read more
Liver cancer - Metabolism (mainly)
Cell line specificityi

RNA specificity category based on RNA sequencing data from cancer cell lines in the Human Protein Atlas grouped according to type of cancer. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.

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Group enriched (Gastric cancer, Kidney cancer, Liver cancer)
PROTEINS IN BLOOD
Detected in blood by
immunoassayi

The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search.

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No (not applicable)
Detected in blood by
mass spectrometryi

Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.

No
Detected in blood by
proximity extension assayi

Detection or not of the gene in blood, based on proximity extension assays (Olink) for a longitudinal wellness study covering 76 individuals with three visits during two years.

Read more
No
PROTEIN FUNCTION
Protein function (UniProt)i

Useful information about the protein provided by UniProt.

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 genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved innate immune response 1, 2, 3, 4. The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in which the monomers are spaced by 1 nucleotide (IR-1) but also to tandem repeat DR1 sites with lower affinity, and can be activated by either FXR or RXR-specific ligands. It is proposed that monomeric nuclear receptors such as NR5A2/LRH-1 bound to coregulatory nuclear responsive element (NRE) halfsites located in close proximity to FXREs modulate transcriptional activity (By similarity). In the liver activates transcription of the corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1 (involved in BA synthesis) implicating at least in part histone demethylase KDM1A resulting in epigenomic repression, and SLC10A1/NTCP (involved in hepatic uptake of conjugated BAs). Activates transcription of the repressor MAFG (involved in regulation of BA synthesis) (By similarity). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine) 5, 6, 7. Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine) 8, 9, 10. In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression 11, 12. The function also involves the coordinated induction of hepatic KLB/beta-klotho expression (By similarity). Regulates transcription of liver UGT2B4 and SULT2A1 involved in BA detoxification; binding to the UGT2B4 promoter seems to imply a monomeric transactivation independent of RXRA 13, 14. Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, PPARA (involved in beta-oxidation of fatty acids), VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly 15, 16, 17. Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance) 18. Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element 19, 20. Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase) 21. Involved in glucose homeostasis by modulating hepatic gluconeogenesis through activation of NR0B2/SHP-mediated repression of respective genes. Modulates glycogen synthesis (inducing phosphorylation of glycogen synthase kinase-3) (By similarity). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance 22. Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier (By similarity). Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells 23. Mediates trans-repression of TLR4-induced cytokine expression; the function seems to require its sumoylation and prevents N-CoR nuclear receptor corepressor clearance from target genes such as IL1B and NOS2 24. Involved in the TLR9-mediated protective mechanism in intestinal inflammation. Plays an anti-inflammatory role in liver inflammation; proposed to inhibit pro-inflammatory (but not antiapoptotic) NF-kappa-B signaling) (By similarity).... show less
Molecular function (UniProt)i

Keywords assigned by UniProt to proteins due to their particular molecular function.

Activator, DNA-binding, Receptor, Repressor
Biological process (UniProt)i

Keywords assigned by UniProt to proteins because they are involved in a particular biological process.

Immunity, Inflammatory response, Innate immunity, Transcription, Transcription regulation
Disease involvementi

Disease related keywords assigned by UniProt combined with Cancer-related genes and FDA approved drug targets

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Disease variant, FDA approved drug targets, Intrahepatic cholestasis
Ligand (UniProt)i

Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.

Metal-binding, Zinc
Gene summary (Entrez)i

Useful information about the gene from 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 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]... show less

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