Details for: TBX18

Gene ID: 9096

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: TBX18

Ensembl ID: ENSG00000112837

Description: T-box transcription factor 18

Cell Significance Landscape

Associated with

  • Cell fate specification
    (GO:0001708)
  • Chromatin
    (GO:0000785)
  • Cochlea morphogenesis
    (GO:0090103)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Dna-binding transcription repressor activity, rna polymerase ii-specific
    (GO:0001227)
  • Morphogenesis of embryonic epithelium
    (GO:0016331)
  • Negative regulation of canonical wnt signaling pathway
    (GO:0090090)
  • Negative regulation of transcription by rna polymerase ii
    (GO:0000122)
  • Neural plate anterior/posterior regionalization
    (GO:0021999)
  • Nucleoplasm
    (GO:0005654)
  • Nucleus
    (GO:0005634)
  • Positive regulation of dna-templated transcription
    (GO:0045893)
  • Protein binding
    (GO:0005515)
  • Protein homodimerization activity
    (GO:0042803)
  • Regulation of sa node cell action potential
    (GO:0098907)
  • Regulation of transcription by rna polymerase ii
    (GO:0006357)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)
  • Rna polymerase ii transcription repressor complex
    (GO:0090571)
  • Sequence-specific double-stranded dna binding
    (GO:1990837)
  • Sinoatrial node cell development
    (GO:0060931)
  • Sinoatrial node cell fate commitment
    (GO:0060930)
  • Sinoatrial node development
    (GO:0003163)
  • Smooth muscle cell differentiation
    (GO:0051145)
  • Somitogenesis
    (GO:0001756)
  • Ureter development
    (GO:0072189)

Significant Cells

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

  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 6.61
    rCSI 8%
    PRS 77.54
  • vascular leptomeningeal cell CL4023051
    CSI 5.11
    rCSI 8.97%
    PRS 92.43
  • mesothelial cell CL0000077
    CSI 4.94
    rCSI 19.33%
    PRS 82.87
  • skin fibroblast CL0002620
    CSI 4.83
    rCSI 4.17%
    PRS 94.1
  • fibroblast of cardiac tissue CL0002548
    CSI 4.82
    rCSI 23.08%
    PRS 95.3
  • melanocyte of skin CL1000458
    CSI 3.8
    rCSI 5.18%
    PRS 69.75
  • basal cell of epidermis CL0002187
    CSI 1.31
    rCSI 2.33%
    PRS 69.9
  • suprabasal keratinocyte CL4033013
    CSI 0.84
    rCSI 1.38%
    PRS 70.22
  • blood vessel smooth muscle cell CL0019018
    CSI 0.6
    rCSI 4.87%
    PRS 93.42

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.

Comma-separated if multiple.
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)

Loading network (please wait)...

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 [TBX18](/details-gene/9096) is a protein-coding gene located on chromosome 6q14.3 that encodes T-box transcription factor 18, a member of the T-box family of transcription factors critical for embryonic development. As a DNA-binding protein, it functions primarily within the [nucleus](/details-cell/GO:0005634) to regulate gene expression, acting as both a transcriptional repressor and activator. Functionally, [TBX18](/details-gene/9096) is implicated in numerous developmental processes, including [somitogenesis](/details-cell/GO:0001756), [sinoatrial node development](/details-cell/GO:0003163), and [ureter development](/details-cell/GO:0072189). Mutations in this gene are associated with urinary tract malformations ([143400](https://omim.org/entry/143400)) ([Link](https://doi.org/10.1016/j.ajhg.2015.07.001)). **Overall**, its expression profile indicates high significance in various mesenchymal-derived cell types, such as [fibroblast of cardiac tissue](/details-cell/CL0002548) and [mesothelial cell](/details-cell/CL0000077), as well as a notable and unexpectedly high significance in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203). ## Cellular Roles and Expression Landscape The expression landscape of [TBX18](/details-gene/9096) suggests a primary role in cells of mesenchymal origin, consistent with its known functions in organogenesis. The gene shows high significance in various stromal and structural cells, including [vascular leptomeningeal cell](/details-cell/CL4023051) (CSI: 5.11), [mesothelial cell](/details-cell/CL0000077) (CSI: 4.94), [skin fibroblast](/details-cell/CL0002620) (CSI: 4.83), and [fibroblast of cardiac tissue](/details-cell/CL0002548) (CSI: 4.82). This broad expression pattern across different fibroblast populations may indicate a fundamental role in maintaining mesenchymal cell identity or function. Notably, the highest significance score for [TBX18](/details-gene/9096) is observed in a mature immune cell type, the [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 6.61). This finding is distinct from its well-characterized developmental roles and suggests a potential, previously unappreciated function in the maintenance or identity of this specific memory T cell subset. Additionally, significant expression is noted in several cell types within the skin, including [melanocyte of skin](/details-cell/CL1000458) (CSI: 3.80) and [basal cell of epidermis](/details-cell/CL0002187) (CSI: 1.31), further highlighting its involvement in diverse tissue contexts. ## Pathways and Molecular Function [TBX18](/details-gene/9096) functions as a sequence-specific transcription factor that can either activate or repress gene expression via [Rna polymerase ii cis-regulatory region sequence-specific dna binding](/details-cell/GO:0000978). Its molecular activities include both [Dna-binding transcription factor activity, rna polymerase ii-specific](/details-cell/GO:0000981) and [Dna-binding transcription repressor activity, rna polymerase ii-specific](/details-cell/GO:0001227). It operates within the [nucleus](/details-cell/GO:0005634), where it can be found associated with [chromatin](/details-cell/GO:0000785). The biological processes associated with [TBX18](/details-gene/9096) are predominantly related to embryonic development. It is a key regulator of [cell fate specification](/details-cell/GO:0001708) and is essential for the morphogenesis of multiple tissues, including the ureter, cochlea, and embryonic epithelium ([Link](https://doi.org/10.1016/j.ajhg.2015.07.001)). Its involvement in [sinoatrial node cell development](/details-cell/GO:0060931) and the [regulation of sa node cell action potential](/details-cell/GO:0098907) underscores its critical role in cardiac pacemaking. Furthermore, its function in [smooth muscle cell differentiation](/details-cell/GO:0051145) is consistent with its observed expression in [blood vessel smooth muscle cell](/details-cell/CL0019018). ## Research Directions The expression profile of [TBX18](/details-gene/9096) presents several intriguing avenues for future research, particularly regarding its unexpected role in the immune system and its potential involvement in tissue homeostasis and pathology. **Proposed Hypotheses:** 1. Given its top significance score in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203), [TBX18](/details-gene/9096) may function as a master regulator that establishes or maintains the transcriptional program specific to this long-lived memory T cell subset, potentially by repressing genes associated with terminal differentiation or apoptosis. 2. The high expression of [TBX18](/details-gene/9096) across multiple fibroblast populations ([skin fibroblast](/details-cell/CL0002620), [fibroblast of cardiac tissue](/details-cell/CL0002548)) suggests it may play a critical role in fibroblast activation during wound healing and in pathological states like fibrosis. It could regulate the differentiation of fibroblasts into myofibroblasts, the primary cell type responsible for excess matrix deposition. **Key Experimental Approach:** To test the hypothesis that [TBX18](/details-gene/9096) is essential for the maintenance of CD8+ memory T cells (Hypothesis 1), a conditional knockout mouse model could be employed. Specifically, deleting *Tbx18* in mature T cells (e.g., using a Cd4-CreERT2 tamoxifen-inducible system) after the establishment of a memory population following viral infection (e.g., with LCMV) would be informative. The subsequent survival, phenotype, and recall capacity of memory CD8+ T cells could be assessed using flow cytometry. Concurrently, ATAC-seq and RNA-seq on sorted memory T cells with and without *Tbx18* deletion would reveal its direct impact on chromatin accessibility and the T cell's transcriptional landscape. **Therapeutic Potential:** As a transcription factor with critical developmental roles, [TBX18](/details-gene/9096) represents a challenging therapeutic target due to the high risk of off-target effects. However, if its activity is proven to be a driver of pathological fibroblast activation in diseases like cardiac or pulmonary fibrosis, developing strategies for its **inhibition** could be beneficial. This might involve small molecules that disrupt its interaction with DNA or essential cofactors. Its specific role in a subset of memory T cells is currently too poorly understood to evaluate its potential as an immunomodulatory target.

Genular Protein ID: 3499963664

Symbol: TBX18_HUMAN

Name: T-box transcription factor TBX18

UniProtKB Accession Codes:

O95935 A2RU13 Q7Z6U4 Q9UJI6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 24 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 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 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

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: 9888994

Title: Identification, mapping and phylogenomic analysis of four new human members of the T-box gene family: EOMES, TBX6, TBX18, and TBX19.

PubMed ID: 9888994

DOI: 10.1006/geno.1998.5632

PubMed ID: 26235987

Title: Mutations in TBX18 cause dominant urinary tract malformations via transcriptional dysregulation of ureter development.

PubMed ID: 26235987

DOI: 10.1016/j.ajhg.2015.07.001

Sequence Information:

  • Length: 607
  • Mass: 64753
  • Checksum: AFDCE41154CA55DA
  • Sequence:
    • MAEKRRGSPC SMLSLKAHAF SVEALIGAEK QQQLQKKRRK LGAEEAAGAV DDGGCSRGGG 
AGEKGSSEGD EGAALPPPAG ATSGPARSGA DLERGAAGGC EDGFQQGASP LASPGGSPKG 
SPARSLARPG TPLPSPQAPR VDLQGAELWK RFHEIGTEMI ITKAGRRMFP AMRVKISGLD 
PHQQYYIAMD IVPVDNKRYR YVYHSSKWMV AGNADSPVPP RVYIHPDSPA SGETWMRQVI 
SFDKLKLTNN ELDDQGHIIL HSMHKYQPRV HVIRKDCGDD LSPIKPVPSG EGVKAFSFPE 
TVFTTVTAYQ NQQITRLKID RNPFAKGFRD SGRNRMGLEA LVESYAFWRP SLRTLTFEDI 
PGIPKQGNAS SSTLLQGTGN GVPATHPHLL SGSSCSSPAF HLGPNTSQLC SLAPADYSAC 
ARSGLTLNRY STSLAETYNR LTNQAGETFA PPRTPSYVGV SSSTSVNMSM GGTDGDTFSC 
PQTSLSMQIS GMSPQLQYIM PSPSSNAFAT NQTHQGSYNT FRLHSPCALY GYNFSTSPKL 
AASPEKIVSS QGSFLGSSPS GTMTDRQMLP PVEGVHLLSS GGQQSFFDSR TLGSLTLSSS 
QVSAHMV