Details for: NR2F6

Gene ID: 2063

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: NR2F6

Ensembl ID: ENSG00000160113

Description: nuclear receptor subfamily 2 group F member 6

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • fallopian tube secretory epithelial cell CL4030006
    CSI 22.97
    rCSI 22.11%
    PRS 86.92
  • placental villous trophoblast CL2000060
    CSI 19.89
    rCSI 30.73%
    PRS 86.58
  • colon epithelial cell CL0011108
    CSI 17.87
    rCSI 18.72%
    PRS 85.56
  • foveolar cell of stomach CL0002179
    CSI 11.58
    rCSI 24.64%
    PRS 90.86
  • bronchus fibroblast of lung CL2000093
    CSI 10.25
    rCSI 8.33%
    PRS 87.41
  • nasal mucosa goblet cell CL0002480
    CSI 9.62
    rCSI 11.15%
    PRS 89.22
  • intestinal epithelial cell CL0002563
    CSI 9.37
    rCSI 9.79%
    PRS 85.65
  • paneth cell CL0000510
    CSI 8.94
    rCSI 13.2%
    PRS 94
  • mesenchymal cell CL0008019
    CSI 6.82
    rCSI 17.31%
    PRS 82.55
  • enterocyte CL0000584
    CSI 6.77
    rCSI 10.92%
    PRS 85.25
  • stem cell CL0000034
    CSI 6.35
    rCSI 6.13%
    PRS 83.31
  • M cell of gut CL0000682
    CSI 5.85
    rCSI 6.21%
    PRS 90.51
  • respiratory suprabasal cell CL4033048
    CSI 5.84
    rCSI 7.48%
    PRS 89.93
  • extravillous trophoblast CL0008036
    CSI 5.56
    rCSI 6.87%
    PRS 86.48
  • epithelial cell of lower respiratory tract CL0002632
    CSI 5.43
    rCSI 4.21%
    PRS 90.95
  • epithelial cell CL0000066
    CSI 5.4
    rCSI 8.29%
    PRS 76.55
  • kidney connecting tubule epithelial cell CL1000768
    CSI 4.86
    rCSI 12.33%
    PRS 80.75
  • ciliated cell CL0000064
    CSI 4.19
    rCSI 6.79%
    PRS 82.46
  • goblet cell CL0000160
    CSI 4.16
    rCSI 3.93%
    PRS 85.92
  • secretory cell CL0000151
    CSI 4.12
    rCSI 4.3%
    PRS 86.93
  • intestine goblet cell CL0019031
    CSI 3.75
    rCSI 3.32%
    PRS 85.54
  • ciliated epithelial cell CL0000067
    CSI 3.44
    rCSI 3.03%
    PRS 78.87
  • neural crest cell CL0011012
    CSI 3.28
    rCSI 2.59%
    PRS 79.84
  • enteroendocrine cell CL0000164
    CSI 3.24
    rCSI 4.42%
    PRS 86.82
  • interstitial cell of Cajal CL0002088
    CSI 3.19
    rCSI 4.06%
    PRS 91.98
  • epithelial cell of lung CL0000082
    CSI 3.16
    rCSI 2.62%
    PRS 89.09
  • pancreatic D cell CL0000173
    CSI 3
    rCSI 2.95%
    PRS 89.63
  • pancreatic A cell CL0000171
    CSI 2.86
    rCSI 3%
    PRS 90.19
  • colonocyte CL1000347
    CSI 2.82
    rCSI 4.05%
    PRS 86.73
  • multi-ciliated epithelial cell CL0005012
    CSI 2.81
    rCSI 2.81%
    PRS 82.27
  • enterocyte of epithelium of large intestine CL0002071
    CSI 2.81
    rCSI 14.74%
    PRS 90.31
  • perivascular cell CL4033054
    CSI 2.75
    rCSI 3.76%
    PRS 91.3
  • ionocyte CL0005006
    CSI 2.66
    rCSI 2.85%
    PRS 89.71
  • acinar cell CL0000622
    CSI 2.61
    rCSI 3.83%
    PRS 93.96
  • basal cell CL0000646
    CSI 2.58
    rCSI 3.45%
    PRS 85.42
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 2.58
    rCSI 5.87%
    PRS 81.07
  • mucous neck cell CL0000651
    CSI 2.56
    rCSI 3.69%
    PRS 91.5
  • respiratory goblet cell CL0002370
    CSI 2.49
    rCSI 27.14%
    PRS 91.87
  • cerebral cortex endothelial cell CL1001602
    CSI 2.46
    rCSI 4.26%
    PRS 81.72
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.45
    rCSI 3.15%
    PRS 84.54
  • radial glial cell CL0000681
    CSI 2.45
    rCSI 3.4%
    PRS 86.49
  • club cell CL0000158
    CSI 2.44
    rCSI 3.57%
    PRS 83.27
  • tracheal goblet cell CL1000329
    CSI 2.43
    rCSI 5.29%
    PRS 91.19
  • duct epithelial cell CL0000068
    CSI 2.29
    rCSI 3.35%
    PRS 91.73
  • transit amplifying cell of colon CL0009011
    CSI 2.27
    rCSI 2.67%
    PRS 88.62
  • pancreatic acinar cell CL0002064
    CSI 2.27
    rCSI 3.02%
    PRS 91.53
  • rod bipolar cell CL0000751
    CSI 2.23
    rCSI 4%
    PRS 82.52
  • lung secretory cell CL1000272
    CSI 2.23
    rCSI 5.51%
    PRS 88.26
  • choroid plexus epithelial cell CL0000706
    CSI 2.15
    rCSI 3.53%
    PRS 79.89
  • hepatocyte CL0000182
    CSI 2.15
    rCSI 3.84%
    PRS 87.02
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.1
    rCSI 4.72%
    PRS 74.13
  • peripheral nervous system neuron CL2000032
    CSI 2.08
    rCSI 2.84%
    PRS 81.3
  • vascular associated smooth muscle cell CL0000359
    CSI 2.08
    rCSI 6.76%
    PRS 86.07
  • pulmonary ionocyte CL0017000
    CSI 2.08
    rCSI 2.53%
    PRS 92.32
  • respiratory basal cell CL0002633
    CSI 2.06
    rCSI 2.13%
    PRS 90.07
  • BEST4+ enteroycte CL4030026
    CSI 2.03
    rCSI 2.53%
    PRS 87.84
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.94
    rCSI 2.32%
    PRS 73.6
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.89
    rCSI 2.44%
    PRS 74.58
  • lung ciliated cell CL1000271
    CSI 1.79
    rCSI 2.07%
    PRS 81.87
  • respiratory hillock cell CL4030023
    CSI 1.79
    rCSI 3.2%
    PRS 92.62
  • squamous epithelial cell CL0000076
    CSI 1.71
    rCSI 4.05%
    PRS 85.96
  • transit amplifying cell CL0009010
    CSI 1.71
    rCSI 2.61%
    PRS 92.08
  • intestinal crypt stem cell of colon CL0009043
    CSI 1.67
    rCSI 12.51%
    PRS 93.59
  • syncytiotrophoblast cell CL0000525
    CSI 1.66
    rCSI 4.77%
    PRS 90.27
  • intestinal tuft cell CL0019032
    CSI 1.65
    rCSI 2.52%
    PRS 90.36
  • lung pericyte CL0009089
    CSI 1.64
    rCSI 4.33%
    PRS 92.43
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.53
    rCSI 2.7%
    PRS 72.92
  • retinal cone cell CL0000573
    CSI 1.53
    rCSI 2.46%
    PRS 79.69
  • kidney epithelial cell CL0002518
    CSI 1.47
    rCSI 2.81%
    PRS 95.69
  • pancreatic ductal cell CL0002079
    CSI 1.42
    rCSI 2.77%
    PRS 89.83
  • retina horizontal cell CL0000745
    CSI 1.41
    rCSI 2.15%
    PRS 85.09
  • type B pancreatic cell CL0000169
    CSI 1.36
    rCSI 3.01%
    PRS 87.93
  • colon goblet cell CL0009039
    CSI 1.33
    rCSI 3.17%
    PRS 90.57
  • pancreatic epsilon cell CL0005019
    CSI 1.32
    rCSI 6.14%
    PRS 92.07
  • bronchial goblet cell CL1000312
    CSI 1.31
    rCSI 5.23%
    PRS 92
  • type L enteroendocrine cell CL0002279
    CSI 1.26
    rCSI 2.36%
    PRS 90.83
  • glandular epithelial cell CL0000150
    CSI 1.22
    rCSI 3.22%
    PRS 94.85
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.2
    rCSI 3.47%
    PRS 87.13
  • tracheobronchial serous cell CL0019001
    CSI 1.12
    rCSI 4.85%
    PRS 91.4
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.1
    rCSI 2.97%
    PRS 90.63
  • deuterosomal cell CL4033044
    CSI 0.97
    rCSI 3.28%
    PRS 83.39
  • mammary gland epithelial cell CL0002327
    CSI 0.89
    rCSI 3.14%
    PRS 92.65
  • transit amplifying cell of small intestine CL0009012
    CSI 0.74
    rCSI 3.26%
    PRS 92.29
  • endothelial cell of placenta CL0009092
    CSI 0.64
    rCSI 3.15%
    PRS 92.63
  • pancreatic stellate cell CL0002410
    CSI 0.61
    rCSI 3.56%
    PRS 89.96
  • acinar cell of salivary gland CL0002623
    CSI 0.36
    rCSI 8.35%
    PRS 94.4
  • peptic cell CL0000155
    CSI 0.35
    rCSI 3.41%
    PRS 93.23
  • pluripotent stem cell CL0002248
    CSI 0.22
    rCSI 6.6%
    PRS 93.7

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [NR2F6](/details-gene/2063) (Nuclear Receptor Subfamily 2 Group F Member 6) is a protein-coding gene located on chromosome 19p13.11. It encodes a nuclear receptor that functions as a ligand-independent transcriptional repressor ([OMIM [132880](https://omim.org/entry/132880)]). As a member of the erbA superfamily of steroid/thyroid hormone receptors, it plays a key role in regulating gene expression through direct DNA binding. **Overall**, expression data reveals that [NR2F6](/details-gene/2063) is a highly significant marker across a diverse range of epithelial tissues, particularly in the female reproductive tract, placenta, and gastrointestinal system. Its established function in suppressing lymphocyte activation, combined with its epithelial expression pattern, suggests a dual role in both maintaining epithelial cell identity and modulating local immune responses. ## Cellular Roles and Expression Landscape The expression profile of [NR2F6](/details-gene/2063) strongly indicates a primary function in epithelial cell biology across multiple organ systems. The gene shows its highest significance in the **Overall** context within secretory and specialized epithelial populations. Most notably, it is a top marker in cells of the female reproductive system and placenta, including [fallopian tube secretory epithelial cell](/details-cell/CL4030006) (CSI: 22.97) and [placental villous trophoblast](/details-cell/CL2000060) (CSI: 19.89). This suggests a critical role in reproductive physiology, potentially related to hormonal regulation and fetal-maternal interface maintenance. Furthermore, [NR2F6](/details-gene/2063) is highly significant throughout the gastrointestinal and respiratory tracts. This includes high expression in [colon epithelial cell](/details-cell/CL0011108) (CSI: 17.87), [foveolar cell of stomach](/details-cell/CL0002179) (CSI: 11.58), [nasal mucosa goblet cell](/details-cell/CL0002480) (CSI: 9.62), and various other intestinal cell types like [paneth cell](/details-cell/CL0000510) and [enterocyte](/details-cell/CL0000584). Its presence in progenitor populations like [stem cell](/details-cell/CL0000034) (CSI: 6.35) is consistent with a role in epithelial differentiation and tissue homeostasis. The broad expression across these diverse mucosal surfaces points to a conserved function in regulating epithelial barrier integrity and function. ## Pathways and Molecular Function Functionally, [NR2F6](/details-gene/2063) is annotated as a transcriptional repressor. Its molecular functions are centered on DNA binding, specifically as a [Dna-binding transcription repressor activity, rna polymerase ii-specific](/details-go/GO0001227) ([GO:0001227](https://www.ebi.ac.uk/QuickGO/term/GO:0001227)) and possessing [Nuclear receptor activity](/details-go/GO0004879) ([GO:0004879](https://www.ebi.ac.uk/QuickGO/term/GO:0004879)). This activity is central to its participation in the [Nuclear receptor transcription pathway](/details-reactome/R-HSA-383280) ([R-HSA-383280](https://reactome.org/content/detail/R-HSA-383280)). The biological processes it regulates are broad, including [Cell differentiation](/details-go/GO0030154) ([GO:0030154](https://www.ebi.ac.uk/QuickGO/term/GO:0030154)) and [Nervous system development](/details-go/GO0007399) ([GO:0007399](https://www.ebi.ac.uk/QuickGO/term/GO:0007399)). Its role in differentiation aligns with its high expression in various specialized epithelial cells and stem cell populations. Research has demonstrated that [NR2F6](/details-gene/2063) (also known as EAR-2) can negatively regulate the function of other nuclear receptors, such as the thyroid hormone receptor ([Link](https://doi.org/10.1128/mcb.20.7.2604-2618.2000)), and can repress transcription of the luteinizing hormone receptor gene ([Link](https://doi.org/10.1210/mend.15.11.0720)), which is consistent with its high significance in reproductive tissues. Additionally, studies have highlighted its critical role as an immune checkpoint, where it suppresses lymphocyte activation and Th17-dependent autoimmunity ([Link](https://doi.org/10.1016/j.immuni.2008.06.008)). ## Research Directions The available data highlights [NR2F6](/details-gene/2063) as a key transcriptional regulator in epithelial tissues with known immune-modulatory functions, opening several avenues for future research. **Proposed Hypotheses:** 1. Given its exceptionally high significance in [fallopian tube secretory epithelial cell](/details-cell/CL4030006) and [placental villous trophoblast](/details-cell/CL2000060), and its documented role in regulating the luteinizing hormone receptor, it is hypothesized that [NR2F6](/details-gene/2063) is a master regulator of epithelial differentiation and hormonal signaling in the female reproductive tract. Its dysregulation may contribute to pathologies such as endometriosis, infertility, or pre-eclampsia. 2. Based on its consistent high expression across diverse intestinal epithelial cells ([colon epithelial cell](/details-cell/CL0011108), [enterocyte](/details-cell/CL0000584), [paneth cell](/details-cell/CL0000510)) and its known function as an immune suppressor, it is hypothesized that [NR2F6](/details-gene/2063) acts as a crucial gatekeeper of intestinal homeostasis by repressing basal inflammatory gene programs within the epithelium, thereby maintaining barrier function and preventing aberrant immune activation. **Experimental Approach:** To test the second hypothesis, a conditional knockout mouse model could be generated with specific deletion of [NR2F6](/details-gene/2063) in intestinal epithelial cells (IECs), for instance, by crossing Nr2f6-floxed mice with a Villin-Cre driver line. These IEC-specific knockout mice and littermate controls could be subjected to an inflammatory challenge, such as dextran sodium sulfate (DSS) in drinking water. The role of [NR2F6](/details-gene/2063) would be assessed by comparing disease severity (weight loss, colon length, histology) between genotypes. Single-cell RNA sequencing of sorted IECs from both groups at baseline and post-challenge would directly reveal whether loss of [NR2F6](/details-gene/2063) leads to de-repression of inflammatory pathways and altered epithelial differentiation programs. **Therapeutic Potential:** As a nuclear receptor, [NR2F6](/details-gene/2063) represents a druggable target. Its established role as a negative regulator of T-cell activation and autoimmunity suggests that enhancing its function could be therapeutically beneficial ([Link](https://doi.org/10.1016/j.immuni.2008.06.008)). The development of small-molecule agonists to bolster the repressive activity of [NR2F6](/details-gene/2063) could represent a novel therapeutic strategy for autoimmune diseases, particularly those affecting mucosal surfaces like inflammatory bowel disease. Activation, rather than inhibition, would be the desired therapeutic approach. However, its widespread expression in critical epithelial tissues would require careful evaluation of potential on-target side effects.

Genular Protein ID: 472922295

Symbol: NR2F6_HUMAN

Name: Nuclear receptor subfamily 2 group F member 6

UniProtKB Accession Codes:

P10588 B2RC68 Q5XGA0 Q6P586 Q9BUE8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 1 ExpressionAtlas 1 GO 16 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 3 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2905047

Title: Identification of two novel members of erbA superfamily by molecular cloning: the gene products of the two are highly related to each other.

PubMed ID: 2905047

DOI: 10.1093/nar/16.23.11057

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 10644740

Title: Nuclear orphan receptors regulate transcription of the gene for the human luteinizing hormone receptor.

PubMed ID: 10644740

DOI: 10.1074/jbc.275.4.2763

PubMed ID: 10713182

Title: The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function.

PubMed ID: 10713182

DOI: 10.1128/mcb.20.7.2604-2618.2000

PubMed ID: 11682620

Title: EAR2 and EAR3/COUP-TFI regulate transcription of the rat LH receptor.

PubMed ID: 11682620

DOI: 10.1210/mend.15.11.0720

PubMed ID: 18701084

Title: The nuclear orphan receptor NR2F6 suppresses lymphocyte activation and T helper 17-dependent autoimmunity.

PubMed ID: 18701084

DOI: 10.1016/j.immuni.2008.06.008

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

Sequence Information:

  • Length: 404
  • Mass: 42979
  • Checksum: D1FFE523E782E969
  • Sequence:
    • MAMVTGGWGG PGGDTNGVDK AGGYPRAAED DSASPPGAAS DAEPGDEERP GLQVDCVVCG 
DKSSGKHYGV FTCEGCKSFF KRSIRRNLSY TCRSNRDCQI DQHHRNQCQY CRLKKCFRVG 
MRKEAVQRGR IPHSLPGAVA ASSGSPPGSA LAAVASGGDL FPGQPVSELI AQLLRAEPYP 
AAAGRFGAGG GAAGAVLGID NVCELAARLL FSTVEWARHA PFFPELPVAD QVALLRLSWS 
ELFVLNAAQA ALPLHTAPLL AAAGLHAAPM AAERAVAFMD QVRAFQEQVD KLGRLQVDSA 
EYGCLKAIAL FTPDACGLSD PAHVESLQEK AQVALTEYVR AQYPSQPQRF GRLLLRLPAL 
RAVPASLISQ LFFMRLVGKT PIETLIRDML LSGSTFNWPY GSGQ