Details for: NKX2 3

Gene ID: 159296

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: NKX2 3

Ensembl ID: ENSG00000119919

Description: NK2 homeobox 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • myofibroblast cell CL0000186
    CSI 11.41
    rCSI 15.8%
    PRS 96.47
  • interstitial cell of Cajal CL0002088
    CSI 7.46
    rCSI 9.5%
    PRS 98.89
  • mesenchymal cell CL0008019
    CSI 5.95
    rCSI 15.11%
    PRS 96.44
  • myeloid leukocyte CL0000766
    CSI 4.87
    rCSI 4.49%
    PRS 98.44
  • stromal cell CL0000499
    CSI 4.67
    rCSI 13.13%
    PRS 96.4
  • mesodermal cell CL0000222
    CSI 3.9
    rCSI 4.68%
    PRS 98.06
  • enteric smooth muscle cell CL0002504
    CSI 3.45
    rCSI 4.93%
    PRS 98.11

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

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
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    • 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 [NKX2 3](/details-gene/159296) is a protein-coding gene located on chromosome 10q24.2 that encodes Nkx-2.3, a member of the NK2 family of homeobox transcription factors. As a sequence-specific DNA-binding protein, it functions as a transcriptional regulator involved in a variety of developmental and homeostatic processes. **Overall**, expression data highlight its primary significance in cells of mesenchymal and myeloid origin, particularly [myofibroblast cell](/details-cell/CL0000186), [interstitial cell of Cajal](/details-cell/CL0002088), and [myeloid leukocyte](/details-cell/CL0000766). Its functional annotations point towards critical roles in organ morphogenesis, particularly of the digestive tract and lymphoid tissues, as well as in the differentiation and homeostasis of various immune cell lineages. ## Cellular Roles and Expression Landscape The expression profile of [NKX2 3](/details-gene/159296) indicates a specialized role in structural and immune cell populations. **Overall**, it shows the highest significance in cells of mesenchymal origin, including [myofibroblast cell](/details-cell/CL0000186) (CSI: 11.41), [interstitial cell of Cajal](/details-cell/CL0002088) (CSI: 7.46), [mesenchymal cell](/details-cell/CL0008019) (CSI: 5.95), and [stromal cell](/details-cell/CL0000499) (CSI: 4.67). Many of these cell types are integral to the architecture and function of the gastrointestinal tract, which is consistent with its known role in gut development. In addition to its role in stromal compartments, [NKX2 3](/details-gene/159296) is also a significant marker for [myeloid leukocyte](/details-cell/CL0000766) (CSI: 4.87). This dual-lineage significance is supported by its functional involvement in both digestive tract morphogenesis and the differentiation of immune cells. This suggests that [NKX2 3](/details-gene/159296) may function at the interface of tissue structure and immune regulation, potentially orchestrating developmental or homeostatic processes that require coordination between stromal and immune compartments. ## Pathways and Molecular Function [NKX2 3](/details-gene/159296) functions primarily as a [DNA-binding transcription factor activity, rna polymerase ii-specific](/details-cell/GO:0000981). It localizes to the [nucleus](/details-cell/GO:0005634) where it binds to [chromatin](/details-cell/GO:0000785) and engages in [rna polymerase ii cis-regulatory region sequence-specific dna binding](/details-cell/GO:0000978) to control gene expression ([GO:0006357](https://www.ebi.ac.uk/QuickGO/term/GO:0006357)). The biological processes governed by [NKX2 3](/details-gene/159296) are predominantly related to development and differentiation. It plays a crucial role in organogenesis, particularly in the formation of secondary lymphoid organs such as the [spleen development](/details-cell/GO:0048536), [lymph node development](/details-cell/GO:0048535), and [Peyer's patch development](/details-cell/GO:0048541). This is complemented by its role in [post-embryonic digestive tract morphogenesis](/details-cell/GO:0048621), aligning with its high expression in gut-associated mesenchymal cells. Furthermore, [NKX2 3](/details-gene/159296) is implicated in the differentiation programs of multiple immune cell types, including [macrophage differentiation](/details-cell/GO:0030225), [plasma cell differentiation](/details-cell/GO:0002317), and [cd4-positive, alpha-beta t cell differentiation](/details-cell/GO:0043367). Its involvement in [leukocyte homeostasis](/details-cell/GO:0001776) and [leukocyte migration](/details-cell/GO:0050900) further solidifies its importance in the regulation of the immune system. ## Research Directions The dual role of [NKX2 3](/details-gene/159296) in both stromal cell biology and immune cell differentiation presents several avenues for future research, especially concerning diseases at the intersection of tissue architecture and immunity, such as inflammatory bowel disease (IBD) or fibrosis. **Proposed Testable Hypotheses:** 1. Given its high expression in gut-associated mesenchymal cells and its role in digestive tract morphogenesis, [NKX2 3](/details-gene/159296) is a critical factor for maintaining intestinal stromal integrity, and its dysregulation contributes to the pathological tissue remodeling and chronic inflammation observed in IBD. 2. Based on its function in both [macrophage differentiation](/details-cell/GO:0030225) and lymphoid organ development, [NKX2 3](/details-gene/159296) acts as a master regulator that coordinates the crosstalk between stromal organizer cells and hematopoietic cells during the formation and maintenance of gut-associated lymphoid tissues (GALT). **Suggested Experimental Approach:** To test the first hypothesis, a conditional knockout mouse model could be generated. Specifically, deleting *Nkx2-3* in intestinal myofibroblasts (e.g., using a *Postn*-Cre driver line) would allow for a precise investigation of its role in the adult gut stroma. These mice could be challenged with an agent that induces colitis, such as dextran sodium sulfate (DSS). The resulting phenotype would be assessed through histology to evaluate tissue damage, intestinal permeability assays, and single-cell RNA sequencing of the colonic tissue to dissect the specific changes in stromal cell identity, extracellular matrix composition, and the recruitment and activation state of immune cell populations. **Therapeutic Potential:** As an intracellular transcription factor, [NKX2 3](/details-gene/159296) is a challenging direct target for conventional small molecule therapeutics. However, if its dysregulation is causally linked to diseases characterized by inflammation and fibrosis, it represents an important node in the disease network. Therapeutic strategies would likely focus on modulating its downstream gene targets or identifying upstream pathways that control its expression or activity. Advanced modalities, such as targeted gene therapy or the development of molecules that disrupt its specific protein-DNA or protein-protein interactions, could hold future promise. The therapeutic goal would likely be to restore homeostatic levels of activity rather than simple inhibition or activation.

Genular Protein ID: 1398081764

Symbol: NKX23_HUMAN

Name: Homeobox protein Nkx-2.3

UniProtKB Accession Codes:

Q8TAU0 B4DUZ4 Q9NYS6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 22 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

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

Sequence Information:

  • Length: 364
  • Mass: 38406
  • Checksum: 10A279CFA3C8A6DB
  • Sequence:
    • MMLPSPVTST PFSVKDILNL EQQHQHFHGA HLQADLEHHF HSAPCMLAAA EGTQFSDGGE 
EDEEDEGEKL SYLNSLAAAD GHGDSGLCPQ GYVHTVLRDS CSEPKEHEEE PEVVRDRSQK 
SCQLKKSLET AGDCKAAEES ERPKPRSRRK PRVLFSQAQV FELERRFKQQ RYLSAPEREH 
LASSLKLTST QVKIWFQNRR YKCKRQRQDK SLELGAHAPP PPPRRVAVPV LVRDGKPCVT 
PSAQAYGAPY SVGASAYSYN SFPAYGYGNS AAAAAAAAAA AAAAAAYSSS YGCAYPAGGG 
GGGGGTSAAT TAMQPACSAA GGGPFVNVSN LGGFGSGGSA QPLHQGTAAG AACAQGTLQG 
IRAW