Details for: TBX3

Gene ID: 6926

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: TBX3

Ensembl ID: ENSG00000135111

Description: T-box transcription factor 3

Cell Significance Landscape

Associated with

Significant Cells

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

  • peripheral nervous system neuron CL2000032
    CSI 19.74
    rCSI 26.9%
    PRS 79.18
  • neural crest cell CL0011012
    CSI 10.87
    rCSI 8.59%
    PRS 77.59
  • placental villous trophoblast CL2000060
    CSI 9.24
    rCSI 14.29%
    PRS 85.11
  • luminal epithelial cell of mammary gland CL0002326
    CSI 8.78
    rCSI 15.95%
    PRS 93.07
  • syncytiotrophoblast cell CL0000525
    CSI 7.16
    rCSI 20.61%
    PRS 89.42
  • BEST4+ enteroycte CL4030026
    CSI 6.75
    rCSI 8.39%
    PRS 86.63
  • stromal cell of ovary CL0002132
    CSI 4.81
    rCSI 13.21%
    PRS 90.7
  • renal interstitial pericyte CL1001318
    CSI 4.8
    rCSI 13.24%
    PRS 82.7
  • Schwann cell CL0002573
    CSI 4.78
    rCSI 13.6%
    PRS 82.25
  • type L enteroendocrine cell CL0002279
    CSI 4.73
    rCSI 8.87%
    PRS 90.06
  • endothelial cell of placenta CL0009092
    CSI 4.63
    rCSI 22.8%
    PRS 91.71
  • pulmonary capillary endothelial cell CL4028001
    CSI 4.23
    rCSI 8.07%
    PRS 93.36
  • cerebral cortex endothelial cell CL1001602
    CSI 4.21
    rCSI 7.29%
    PRS 79.77
  • fibroblast of lung CL0002553
    CSI 3.99
    rCSI 3.72%
    PRS 87.4
  • pancreatic stellate cell CL0002410
    CSI 3.92
    rCSI 22.8%
    PRS 88.68
  • skin fibroblast CL0002620
    CSI 3.86
    rCSI 3.33%
    PRS 85.98
  • midzonal region hepatocyte CL0019028
    CSI 3.83
    rCSI 8.98%
    PRS 85.01
  • bronchus fibroblast of lung CL2000093
    CSI 3.74
    rCSI 3.04%
    PRS 85.87
  • myofibroblast cell CL0000186
    CSI 3.74
    rCSI 5.18%
    PRS 82.95
  • enteroendocrine cell CL0000164
    CSI 3.58
    rCSI 4.89%
    PRS 85.48
  • tracheobronchial smooth muscle cell CL0019019
    CSI 3.51
    rCSI 6.19%
    PRS 89.98
  • basal-myoepithelial cell of mammary gland CL0002324
    CSI 3.41
    rCSI 6.44%
    PRS 93.17
  • stem cell CL0000034
    CSI 3.37
    rCSI 3.25%
    PRS 81.43
  • intestine goblet cell CL0019031
    CSI 3.12
    rCSI 2.77%
    PRS 83.96
  • vascular associated smooth muscle cell CL0000359
    CSI 3.11
    rCSI 10.08%
    PRS 84.41
  • enteric neuron CL0007011
    CSI 2.98
    rCSI 43.99%
    PRS 89.45
  • interstitial cell of Cajal CL0002088
    CSI 2.94
    rCSI 3.74%
    PRS 90.52
  • perivascular cell CL4033054
    CSI 2.84
    rCSI 3.88%
    PRS 90.12
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.83
    rCSI 3.1%
    PRS 88.02
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.81
    rCSI 4.48%
    PRS 89.58
  • type EC enteroendocrine cell CL0000577
    CSI 2.7
    rCSI 9.58%
    PRS 88.53
  • goblet cell CL0000160
    CSI 2.67
    rCSI 2.53%
    PRS 84.54
  • enteric smooth muscle cell CL0002504
    CSI 2.49
    rCSI 3.55%
    PRS 86.87
  • tendon cell CL0000388
    CSI 2.46
    rCSI 6.4%
    PRS 90.64
  • M cell of gut CL0000682
    CSI 2.41
    rCSI 2.56%
    PRS 89.45
  • enterocyte CL0000584
    CSI 2.39
    rCSI 3.85%
    PRS 84.12
  • adventitial cell CL0002503
    CSI 2.31
    rCSI 5.51%
    PRS 89.22
  • enteroendocrine cell of small intestine CL0009006
    CSI 2.25
    rCSI 4.96%
    PRS 90.97
  • lung endothelial cell CL1001567
    CSI 2.1
    rCSI 4.91%
    PRS 93.62
  • pulmonary artery endothelial cell CL1001568
    CSI 2.09
    rCSI 2.84%
    PRS 92.24
  • colonocyte CL1000347
    CSI 2.05
    rCSI 2.94%
    PRS 85.61
  • small intestine goblet cell CL1000495
    CSI 2.04
    rCSI 4.47%
    PRS 89.97
  • blood vessel endothelial cell CL0000071
    CSI 2.01
    rCSI 4.16%
    PRS 84.01
  • mesenchymal cell CL0008019
    CSI 1.91
    rCSI 4.86%
    PRS 80.39
  • lung microvascular endothelial cell CL2000016
    CSI 1.91
    rCSI 36.9%
    PRS 91.69
  • cardiac neuron CL0010022
    CSI 1.91
    rCSI 6.1%
    PRS 84.5
  • centrilobular region hepatocyte CL0019029
    CSI 1.9
    rCSI 4.95%
    PRS 83.47
  • hepatocyte CL0000182
    CSI 1.89
    rCSI 3.39%
    PRS 85.64
  • intestinal tuft cell CL0019032
    CSI 1.79
    rCSI 2.73%
    PRS 88.99
  • extravillous trophoblast CL0008036
    CSI 1.74
    rCSI 2.15%
    PRS 84.73
  • chondrocyte CL0000138
    CSI 1.72
    rCSI 2.73%
    PRS 80.78
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.72
    rCSI 4.62%
    PRS 89.44
  • lung pericyte CL0009089
    CSI 1.71
    rCSI 4.5%
    PRS 91.24
  • stromal cell CL0000499
    CSI 1.65
    rCSI 4.63%
    PRS 81.78
  • myoepithelial cell CL0000185
    CSI 1.64
    rCSI 4.16%
    PRS 89.76
  • basal cell CL0000646
    CSI 1.62
    rCSI 2.17%
    PRS 84.1
  • cardiac endothelial cell CL0010008
    CSI 1.61
    rCSI 6.51%
    PRS 86.89
  • glycinergic amacrine cell CL4030028
    CSI 1.6
    rCSI 4.17%
    PRS 80.56
  • enteroglial cell CL4040002
    CSI 1.59
    rCSI 8.35%
    PRS 87.2
  • paneth cell of epithelium of small intestine CL1000343
    CSI 1.58
    rCSI 4.43%
    PRS 90.85
  • alveolar adventitial fibroblast CL4028006
    CSI 1.56
    rCSI 2.46%
    PRS 87.4
  • mesodermal cell CL0000222
    CSI 1.52
    rCSI 1.83%
    PRS 84.74
  • paneth cell CL0000510
    CSI 1.39
    rCSI 2.05%
    PRS 93.18
  • melanocyte of skin CL1000458
    CSI 1.39
    rCSI 1.9%
    PRS 55.08
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.38
    rCSI 3.99%
    PRS 85.71
  • basal cell of prostate epithelium CL0002341
    CSI 1.33
    rCSI 3.85%
    PRS 90.6
  • fibroblast of breast CL4006000
    CSI 1.3
    rCSI 5.48%
    PRS 89.23
  • endothelial cell of uterus CL0009095
    CSI 1.27
    rCSI 9.25%
    PRS 91.83
  • GABAergic amacrine cell CL4030027
    CSI 1.2
    rCSI 4.12%
    PRS 73.05
  • mammary gland epithelial cell CL0002327
    CSI 1.07
    rCSI 3.74%
    PRS 91.73
  • mesangial cell CL0000650
    CSI 1.03
    rCSI 4.19%
    PRS 92.61
  • luminal cell of prostate epithelium CL0002340
    CSI 0.77
    rCSI 4.13%
    PRS 91.92
  • vein endothelial cell of respiratory system CL4033008
    CSI 0.46
    rCSI 3.18%
    PRS 90.61
  • odontoblast CL0000060
    CSI 0.4
    rCSI 9.02%
    PRS 92.63
  • blood vessel smooth muscle cell CL0019018
    CSI 0.36
    rCSI 2.9%
    PRS 82.27
  • enterocyte of epithelium of small intestine CL1000334
    CSI 0.3
    rCSI 4.66%
    PRS 90.93
  • mesenchymal stem cell CL0000134
    CSI 0.25
    rCSI 2.74%
    PRS 89.41

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 [TBX3](/details-gene/6926) (T-box transcription factor 3) is a protein-coding gene located on chromosome 12q24.21. It encodes a transcription factor that plays a crucial, pleiotropic role in embryonic development, particularly in the morphogenesis of limbs, heart, and mammary glands. As a member of the T-box family, [TBX3](/details-gene/6926) can function as both a transcriptional activator and repressor, regulating key cellular processes such as cell fate specification, proliferation, and senescence. Its expression is highly significant in diverse cell types, including [peripheral nervous system neuron](/details-cell/CL2000032), [neural crest cell](/details-cell/CL0011012), and various placental and mammary epithelial cells. Clinically, heterozygous mutations in [TBX3](/details-gene/6926) are the cause of Ulnar-Mammary Syndrome ([181450](https://omim.org/entry/181450), [601621](https://omim.org/entry/601621)), a congenital disorder characterized by defects in the limbs, apocrine glands, teeth, and genital development [Link](https://doi.org/10.1038/ng0797-311). ## Cellular Roles and Expression Landscape The expression profile of [TBX3](/details-gene/6926) underscores its fundamental role in development and specialized tissue function. **Overall**, the gene shows the highest significance in cell types derived from multiple germ layers, highlighting its broad developmental impact. Its most prominent role is suggested in neuroectodermal lineages, with the highest Cell Significance Index (CSI) observed in [peripheral nervous system neuron](/details-cell/CL2000032) (CSI: 19.74) and its progenitor, the [neural crest cell](/details-cell/CL0011012) (CSI: 10.87). This indicates that [TBX3](/details-gene/6926) is a defining transcriptional regulator in the specification or maintenance of the peripheral nervous system. [TBX3](/details-gene/6926) is also a key marker in placental development, evidenced by its high significance in [placental villous trophoblast](/details-cell/CL2000060) (CSI: 9.24) and [syncytiotrophoblast cell](/details-cell/CL0000525) (CSI: 7.16). This expression pattern is consistent with its involvement in embryonic and extra-embryonic tissue formation. Furthermore, its high CSI in [luminal epithelial cell of mammary gland](/details-cell/CL0002326) (CSI: 8.78) directly aligns with its known function in mammary gland morphogenesis and its association with Ulnar-Mammary Syndrome. The gene's significance extends to various stromal, mesenchymal, and endothelial cell types, such as [stromal cell of ovary](/details-cell/CL0002132) and [renal interstitial pericyte](/details-cell/CL1001318), suggesting a broader role in organ architecture and support. ## Pathways and Molecular Function The functional annotations for [TBX3](/details-gene/6926) confirm its identity as a master developmental regulator located in the [nucleus](/details-cell/GO:0005634) and acting upon [chromatin](/details-cell/GO:0000785). Its primary molecular function is as a sequence-specific DNA-binding transcription factor ([GO:0043565](https://www.ebi.ac.uk/QuickGO/term/GO:0043565)) that can both activate ([GO:0001228](https://www.ebi.ac.uk/QuickGO/term/GO:0001228)) and repress ([GO:0001227](https://www.ebi.ac.uk/QuickGO/term/GO:0001227)) transcription from RNA polymerase II promoters. Research has confirmed its role as a transcriptional repressor, for example in the regulation of the p14ARF tumor suppressor gene [Link](https://doi.org/10.1074/jbc.m200403200). Biologically, [TBX3](/details-gene/6926) is implicated in a vast array of morphogenetic processes, as reflected in the overarching Reactome pathway, [Developmental biology](/details-pathway/R-HSA-1266738). GO annotations specify its critical involvement in the development of numerous structures, including limbs ([GO:0035115](https://www.ebi.ac.uk/QuickGO/term/GO:0035115)), heart ([GO:0001947](https://www.ebi.ac.uk/QuickGO/term/GO:0001947)), and mammary glands ([GO:0030879](https://www.ebi.ac.uk/QuickGO/term/GO:0030879)). These functions directly correspond to the clinical features of Ulnar-Mammary Syndrome. Furthermore, [TBX3](/details-gene/6926) is a key regulator of fundamental cellular decisions. It participates in `cell fate specification` ([GO:0001708](https://www.ebi.ac.uk/QuickGO/term/GO:0001708)) and controls cell proliferation, both positively ([GO:0008284](https://www.ebi.ac.uk/QuickGO/term/GO:0008284)) and negatively. Notably, it is also involved in the regulation of `cellular senescence` ([GO:0090398](https://www.ebi.ac.uk/QuickGO/term/GO:0090398)) and `negative regulation of apoptotic process` ([GO:0043066](https://www.ebi.ac.uk/QuickGO/term/GO:0043066)), functions that are often co-opted in cancer. ## Research Directions While the role of [TBX3](/details-gene/6926) in congenital disease is well-established, its specific functions in the diverse cell types identified by expression profiling present new avenues for research. Its established role as a developmental regulator that also controls senescence and proliferation makes it a gene of interest in both regenerative medicine and oncology. Based on the available data, several testable hypotheses can be proposed: 1. Given its top-ranking significance in [peripheral nervous system neuron](/details-cell/CL2000032) and [neural crest cell](/details-cell/CL0011012), [TBX3](/details-gene/6926) may function as a master regulator that maintains neuronal identity by actively repressing mesenchymal or other alternative lineage programs in these cells. 2. The high expression of [TBX3](/details-gene/6926) in [placental villous trophoblast](/details-cell/CL2000060) and [syncytiotrophoblast cell](/details-cell/CL0000525) suggests it is essential for trophoblast differentiation and cell fusion, processes critical for establishing the maternal-fetal interface. Dysregulation of [TBX3](/details-gene/6926) could therefore contribute to placental insufficiency disorders. A compelling experimental approach to test the second hypothesis would involve using a human trophoblast stem cell (hTSC) model. A CRISPR-Cas9-mediated knockout of [TBX3](/details-gene/6926) in hTSCs could be performed. These modified cells would then be induced to differentiate, and the efficiency of syncytiotrophoblast formation would be quantified via immunofluorescence for markers like beta-hCG and visualization of multinucleated syncytia. RNA-sequencing of the knockout cells during differentiation would reveal the downstream transcriptional networks controlled by [TBX3](/details-gene/6926) that govern placental development. From a therapeutic perspective, [TBX3](/details-gene/6926) represents a complex target. In the context of Ulnar-Mammary Syndrome, which is caused by haploinsufficiency, a gene activation or replacement strategy would be needed but is currently infeasible. Conversely, [TBX3](/details-gene/6926) is overexpressed in several cancers, including melanoma and breast cancer, where it promotes proliferation and bypasses senescence. In these oncogenic contexts, **inhibition** of [TBX3](/details-gene/6926) is the desired therapeutic strategy. As a transcription factor, it is difficult to target directly with small molecules, but approaches aimed at disrupting its protein-protein interactions or its binding to DNA could be explored. The broad expression of [TBX3](/details-gene/6926) in multiple healthy tissues suggests that systemic inhibitors could have significant toxicity, necessitating the development of highly targeted delivery systems or context-dependent inhibitors.

Genular Protein ID: 2956653309

Symbol: TBX3_HUMAN

Name: T-box transcription factor TBX3

UniProtKB Accession Codes:

O15119 Q8TB20 Q9UKF8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 64 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 1 RefSeq 2 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: 10468588

Title: Transcription repression by Xenopus ET and its human ortholog TBX3, a gene involved in ulnar-mammary syndrome.

PubMed ID: 10468588

DOI: 10.1073/pnas.96.18.10212

PubMed ID: 9207801

Title: Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome.

PubMed ID: 9207801

DOI: 10.1038/ng0797-311

PubMed ID: 10330342

Title: The spectrum of mutations in TBX3: genotype/phenotype relationship in ulnar-mammary syndrome.

PubMed ID: 10330342

DOI: 10.1086/302417

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: 12000749

Title: The T-box repressors TBX2 and TBX3 specifically regulate the tumor suppressor gene p14ARF via a variant T-site in the initiator.

PubMed ID: 12000749

DOI: 10.1074/jbc.m200403200

PubMed ID: 18220336

Title: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.

PubMed ID: 18220336

DOI: 10.1021/pr0705441

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: 22002537

Title: Physical and functional interaction between PML and TBX2 in the establishment of cellular senescence.

PubMed ID: 22002537

DOI: 10.1038/emboj.2011.370

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

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

PubMed ID: 12005433

Title: Structure of the DNA-bound T-box domain of human TBX3, a transcription factor responsible for ulnar-mammary syndrome.

PubMed ID: 12005433

DOI: 10.1016/s0969-2126(02)00722-0

Sequence Information:

  • Length: 743
  • Mass: 79389
  • Checksum: D5572F9CF871E89F
  • Sequence:
    • MSLSMRDPVI PGTSMAYHPF LPHRAPDFAM SAVLGHQPPF FPALTLPPNG AAALSLPGAL 
AKPIMDQLVG AAETGIPFSS LGPQAHLRPL KTMEPEEEVE DDPKVHLEAK ELWDQFHKRG 
TEMVITKSGR RMFPPFKVRC SGLDKKAKYI LLMDIIAADD CRYKFHNSRW MVAGKADPEM 
PKRMYIHPDS PATGEQWMSK VVTFHKLKLT NNISDKHGFT LAFPSDHATW QGNYSFGTQT 
ILNSMHKYQP RFHIVRANDI LKLPYSTFRT YLFPETEFIA VTAYQNDKIT QLKIDNNPFA 
KGFRDTGNGR REKRKQLTLQ SMRVFDERHK KENGTSDESS SEQAAFNCFA QASSPAASTV 
GTSNLKDLCP SEGESDAEAE SKEEHGPEAC DAAKISTTTS EEPCRDKGSP AVKAHLFAAE 
RPRDSGRLDK ASPDSRHSPA TISSSTRGLG AEERRSPVRE GTAPAKVEEA RALPGKEAFA 
PLTVQTDAAA AHLAQGPLPG LGFAPGLAGQ QFFNGHPLFL HPSQFAMGGA FSSMAAAGMG 
PLLATVSGAS TGVSGLDSTA MASAAAAQGL SGASAATLPF HLQQHVLASQ GLAMSPFGSL 
FPYPYTYMAA AAAASSAAAS SSVHRHPFLN LNTMRPRLRY SPYSIPVPVP DGSSLLTTAL 
PSMAAAAGPL DGKVAALAAS PASVAVDSGS ELNSRSSTLS SSSMSLSPKL CAEKEAATSE 
LQSIQRLVSG LEAKPDRSRS ASP