Details for: TBX19

Gene ID: 9095

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: TBX19

Ensembl ID: ENSG00000143178

Description: T-box transcription factor 19

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Anatomical structure morphogenesis
    (GO:0009653)
  • Cell fate specification
    (GO:0001708)
  • Chromatin
    (GO:0000785)
  • Dna-binding transcription activator activity, rna polymerase ii-specific
    (GO:0001228)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Heart morphogenesis
    (GO:0003007)
  • Mesoderm formation
    (GO:0001707)
  • Nucleus
    (GO:0005634)
  • Pituitary gland development
    (GO:0021983)
  • Positive regulation of transcription by rna polymerase ii
    (GO:0045944)
  • Protein binding
    (GO:0005515)
  • Regulation of cell differentiation
    (GO:0045595)
  • Regulation of cell population proliferation
    (GO:0042127)
  • Regulation of transcription by rna polymerase ii
    (GO:0006357)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)
  • Sequence-specific double-stranded dna binding
    (GO:1990837)

Significant Cells

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

  • chondrocyte CL0000138
    CSI 2.24
    rCSI 3.57%
    PRS 97.54

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)

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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 [TBX19](/details-gene/9095), or T-box transcription factor 19, is a protein-coding gene located on chromosome 1q24.2. As a member of the T-box family of transcription factors, it plays a critical role in developmental processes by binding to DNA and regulating gene expression. Functionally, [TBX19](/details-gene/9095) is essential for [pituitary gland development](/details-cell/GO:0021983) and is particularly known for its role in the specification of pro-opiomelanocortin (POMC)-expressing cells in the anterior pituitary ([Link](https://doi.org/10.1016/s0092-8674(01)00282-3)). Mutations in this gene are clinically associated with isolated congenital adrenocorticotropic hormone (ACTH) deficiency ([201400](https://omim.org/entry/201400)). While its function in the pituitary is well-established, expression data suggests a potentially significant role in other cell lineages, with its highest significance observed in [chondrocyte](/details-cell/CL0000138). ## Cellular Roles and Expression Landscape The primary function of [TBX19](/details-gene/9095) is well-characterized in the pituitary gland, where, under the name Tpit, it acts as a cell-restricted transcription factor essential for the terminal differentiation of corticotroph and melanotroph lineages. It activates POMC transcription, which is the precursor for ACTH, in cooperation with Pitx homeodomain proteins ([Link](https://doi.org/10.1016/s0092-8674(01)00282-3)). However, a broader analysis of its expression landscape reveals a highly specific pattern. * **Overall**, the most significant expression signal for [TBX19](/details-gene/9095) is found in [chondrocyte](/details-cell/CL0000138) (CSI: 2.24). This suggests a potential and perhaps under-investigated role for this transcription factor in cartilage development, maintenance, or homeostasis, extending its functional repertoire beyond neuroendocrine development. The highly specific expression in these distinct developmental lineages underscores its role as a master regulator of cell fate specification. ## Pathways and Molecular Function [TBX19](/details-gene/9095) functions as a sequence-specific DNA-binding transcription factor that primarily resides in the [nucleus](/details-cell/GO:0005634) and interacts with [chromatin](/details-cell/GO:0000785). Its molecular activity is centered on the [positive regulation of transcription by rna polymerase ii](/details-cell/GO:0045944), consistent with its role as a transcriptional activator. The biological processes governed by [TBX19](/details-gene/9095) are fundamental to embryonic development. Its most critical role is in [pituitary gland development](/details-cell/GO:0021983), where it drives [cell fate specification](/details-cell/GO:0001708). Its involvement in broader developmental programs is suggested by its association with processes such as [anatomical structure morphogenesis](/details-cell/GO:0009653), [mesoderm formation](/details-cell/GO:0001707), and [heart morphogenesis](/details-cell/GO:0003007), as identified in a phylogenomic analysis of the T-box family ([Link](https://doi.org/10.1006/geno.1998.5632)). This portfolio of functions highlights its importance as a key node in the regulatory networks controlling the formation of multiple organ systems. ## Research Directions The well-defined role of [TBX19](/details-gene/9095) in pituitary development contrasts with emerging data suggesting its significance in chondrocytes, opening new avenues for investigation. ### Proposed Hypotheses 1. **[TBX19](/details-gene/9095) is a key transcriptional regulator in chondrogenesis.** The high expression significance observed in [chondrocyte](/details-cell/CL0000138) suggests that, analogous to its function in the pituitary, [TBX19](/details-gene/9095) may regulate a specific suite of genes essential for cartilage matrix production or the maintenance of the chondrocyte phenotype. 2. **Disease-associated mutations in [TBX19](/details-gene/9095) disrupt protein-protein interactions essential for transcriptional activation.** The pathology of isolated ACTH deficiency ([201400](https://omim.org/entry/201400)) may arise not only from impaired DNA binding but also from the failure of mutant [TBX19](/details-gene/9095) to recruit or interact with co-activators like Pitx proteins at the POMC promoter, leading to a selective failure of gene expression. ### Experimental Approach To test the first hypothesis regarding its role in chondrocytes, a functional genomics approach could be employed. Specifically, CRISPR-Cas9 could be used to knock out [TBX19](/details-gene/9095) in a human mesenchymal stem cell line or a chondrogenic cell line like ATDC5. Following induction of chondrogenic differentiation, the impact of the knockout could be assessed via RNA-sequencing to identify downstream target genes and by biochemical assays (e.g., Alcian blue staining for proteoglycans, Western blotting for collagen type II) to measure defects in cartilage matrix formation. ### Therapeutic Potential Given that loss-of-function mutations in [TBX19](/details-gene/9095) cause a deficiency syndrome, it is not a suitable target for therapeutic inhibition. Instead, its therapeutic potential lies in the realm of regenerative medicine or gene therapy. For congenital ACTH deficiency, restoring [TBX19](/details-gene/9095) function in pituitary progenitor cells could be a long-term therapeutic strategy. Furthermore, if its role in chondrogenesis is confirmed, it could be explored as a target for *activation* or as a tool to enhance the differentiation of stem cells into functional chondrocytes for cartilage repair applications.

Genular Protein ID: 1320959104

Symbol: TBX19_HUMAN

Name: T-box factor, pituitary

UniProtKB Accession Codes:

O60806 Q52M53

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 14 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRINTS 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

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: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 11290323

Title: A pituitary cell-restricted T-box factor, Tpit, activates POMC transcription in cooperation with Pitx homeoproteins.

PubMed ID: 11290323

DOI: 10.1016/s0092-8674(01)00282-3

Sequence Information:

  • Length: 448
  • Mass: 48238
  • Checksum: B7B1DFF14B8B53C5
  • Sequence:
    • MAMSELGTRK PSDGTVSHLL NVVESELQAG REKGDPTEKQ LQIILEDAPL WQRFKEVTNE 
MIVTKNGRRM FPVLKISVTG LDPNAMYSLL LDFVPTDSHR WKYVNGEWVP AGKPEVSSHS 
CVYIHPDSPN FGAHWMKAPI SFSKVKLTNK LNGGGQIMLN SLHKYEPQVH IVRVGSAHRM 
VTNCSFPETQ FIAVTAYQNE EITALKIKYN PFAKAFLDAK ERNHLRDVPE AISESQHVTY 
SHLGGWIFSN PDGVCTAGNS NYQYAAPLPL PAPHTHHGCE HYSGLRGHRQ APYPSAYMHR 
NHSPSVNLIE SSSNNLQVFS GPDSWTSLSS TPHASILSVP HTNGPINPGP SPYPCLWTIS 
NGAGGPSGPG PEVHASTPGA FLLGNPAVTS PPSVLSTQAP TSAGVEVLGE PSLTSIAVST 
WTAVASHPFA GWGGPGAGGH HSPSSLDG

Genular Protein ID: 338290663

Symbol: B3KRD9_HUMAN

Name: N/A

UniProtKB Accession Codes:

B3KRD9

Database IDs:

ARBA 5 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 7 Gene3D 1 InterPro 6 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 2 PROSITE 3 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 RefSeq 1 SMART 1 SUPFAM 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 316
  • Mass: 33598
  • Checksum: 2F652B3F57B6621E
  • Sequence:
    • MFPVLKISVT GLDPNAMYSL LLDFVPTDSH RWKYVNGEWV PAGKPEVSSH SCVYIHPDSP 
NFGAHWMKAP ISFSKVKLTN KLNGGGQIML NSLHKYEPQV HIVRVGSAHR MVTNCSFPET 
QFIAVTAYQN EEITALKIKY NPFAKAFLDA KERNHLRDVP EAISESQHVT YSHLNLIESS 
SNNLQVFSGP DSWTSLSSTP HASILSVPHT NGPINPGPSP YPCLWTISNG AGGPSGPGPE 
VHASTPGAFL LGNPAVTSPP SVLSTQAPTS AGVEVLGEPS LTSIAVSTWT AVASHPFAGW 
GGPGAGGHHS PSSLDG