| HGNC Family | T-boxes (TBX) |
| Name | T-box 4 |
| Description | This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is the human homolog of mouse Tbx4, which is closely linked to Tbx2 on mouse chromosome 11. Similarly this gene, like TBX2, maps to human chromosome 17. Expression studies in mouse and chicken show that Tbx4 is expressed in developing hindlimb, but not in forelimb buds, suggesting a role for this gene in regulating limb development and specification of limb identity. [provided by RefSeq, Jul 2008] |
| Summary |
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In several studies, TBX4 alterations have been directly linked to aberrant hindlimb outgrowth and skeletal patterning defects, underscoring its pivotal role in normal mesenchymal differentiation and lower limb organogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in limb morphogenesis, TBX4 is indispensable for normal lung development and pulmonary homeostasis. It orchestrates critical epithelial–mesenchymal signaling—most notably via the TBX4–FGF10 axis—that is necessary for proper lung branching morphogenesis, distal lung growth, and alveolar formation. Disruption of TBX4 function, whether by mutation or epigenetic silencing, has been implicated in a broad spectrum of pulmonary disorders including pediatric pulmonary arterial hypertension, congenital lung hypoplasias (such as acinar dysplasia and pulmonary hypoplasia), and lung fibrosis. Experimental lineage‐tracing and functional studies further reveal that TBX4‐expressing mesenchymal progenitors serve as a major source of myofibroblasts contributing to extracellular matrix remodeling and pathologic fibrotic responses, while genetic screening in patients with heritable pulmonary arterial hypertension has confirmed TBX4 as a pathogenic contributor. These converging data highlight TBX4 as a central transcriptional regulator in lung organogenesis and disease pathogenesis, with potential implications as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also suggests that TBX4 expression may extend its clinical relevance into oncology. In pancreatic ductal adenocarcinoma, for instance, reduced TBX4 expression correlates with adverse prognostic outcomes, indicating a potential role as a tumor biomarker and implying that TBX4-mediated transcriptional networks might influence tumor biology in contexts beyond embryonic development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ernie M H F Bongers, Pascal H G Duijf, Sylvia E M van Beersum, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Computed tomographic findings in TBX4 mutation: a common cause of severe pulmonary artery hypertension in children."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Radiol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00247-023-05848-7"}], "href": "https://doi.org/10.1007/s00247-023-05848-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38191808"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38191808"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Meijuan Zong, Meng Meng, Liang Li "}, {"type": "b", "children": [{"type": "t", "text": "Low expression of TBX4 predicts poor prognosis in patients with stage II pancreatic ductal adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms12084953"}], "href": "https://doi.org/10.3390/ijms12084953"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21954337"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21954337"}]}]}]}
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| Synonyms | ICPPS |
| Proteins | TBX4_HUMAN |
| NCBI Gene ID | 9496 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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TBX4 has 4,243 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 95 datasets.
Click the + buttons to view associations for TBX4 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Achilles Cell Line Gene Essentiality Profiles | cell lines with fitness changed by TBX4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset. | |
| Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles | tissues with high or low expression of TBX4 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of TBX4 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of TBX4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| BioGPS Cell Line Gene Expression Profiles | cell lines with high or low expression of TBX4 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of TBX4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| BioGPS Mouse Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of TBX4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset. | |
| Carcinogenome Chemical Perturbation Carcinogenicity Signatures | small molecule perturbations changing expression of TBX4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of TBX4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| CCLE Cell Line Gene Expression Profiles | cell lines with high or low expression of TBX4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| CellMarker Gene-Cell Type Associations | cell types associated with TBX4 gene from the CellMarker Gene-Cell Type Associations dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of TBX4 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of TBX4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of TBX4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| ClinVar Gene-Phenotype Associations | phenotypes associated with TBX4 gene from the curated ClinVar Gene-Phenotype Associations dataset. | |
| ClinVar Gene-Phenotype Associations 2025 | phenotypes associated with TBX4 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing TBX4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with TBX4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with TBX4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of TBX4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with TBX4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| CTD Gene-Disease Associations | diseases associated with TBX4 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by TBX4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with TBX4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with TBX4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with TBX4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with TBX4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with TBX4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at TBX4 gene from the ENCODE Histone Modification Site Profiles dataset. | |
| ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of TBX4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of TBX4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| ESCAPE Omics Signatures of Genes and Proteins for Stem Cells | PubMedIDs of publications reporting gene signatures containing TBX4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
| GAD Gene-Disease Associations | diseases associated with TBX4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
| GAD High Level Gene-Disease Associations | diseases associated with TBX4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset. | |
| GDSC Cell Line Gene Expression Profiles | cell lines with high or low expression of TBX4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with TBX4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing TBX4 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of TBX4 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of TBX4 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of TBX4 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of TBX4 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of TBX4 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of TBX4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving TBX4 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving TBX4 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving TBX4 gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing TBX4 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Cellular Component Annotations 2025 | cellular components containing TBX4 protein from the curated GO Cellular Component Annotations 2025 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by TBX4 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2023 | molecular functions performed by TBX4 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by TBX4 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of TBX4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of TBX4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GTEx Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of TBX4 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with TBX4 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| GWASdb SNP-Disease Associations | diseases associated with TBX4 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset. | |
| GWASdb SNP-Phenotype Associations | phenotypes associated with TBX4 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of TBX4 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HPA Cell Line Gene Expression Profiles | cell lines with high or low expression of TBX4 gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of TBX4 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| HPA Tissue Protein Expression Profiles | tissues with high or low expression of TBX4 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
| HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of TBX4 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
| HPO Gene-Disease Associations | phenotypes associated with TBX4 gene by mapping known disease genes to disease phenotypes from the HPO Gene-Disease Associations dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with TBX4 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| IMPC Knockout Mouse Phenotypes | phenotypes of mice caused by TBX4 gene knockout from the IMPC Knockout Mouse Phenotypes dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for TBX4 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of TBX4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Mouse Transcription Factor Targets 2025 | transcription factors regulating expression of TBX4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of TBX4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of TBX4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles | cell lines with TBX4 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of TBX4 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LINCS L1000 CMAP Chemical Perturbation Consensus Signatures | small molecule perturbations changing expression of TBX4 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by TBX4 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| MiRTarBase microRNA Targets | microRNAs targeting TBX4 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of TBX4 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| MPO Gene-Phenotype Associations | phenotypes of transgenic mice caused by TBX4 gene mutations from the MPO Gene-Phenotype Associations dataset. | |
| NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles | drug perturbations changing expression of TBX4 gene from the NIBR DRUG-seq U2OS MoA Box dataset. | |
| OMIM Gene-Disease Associations | phenotypes associated with TBX4 gene from the curated OMIM Gene-Disease Associations dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for TBX4 from the Pathway Commons Protein-Protein Interactions dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of TBX4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations | gene perturbations changing expression of TBX4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving TBX4 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving TBX4 protein from the Wikipathways PFOCR 2024 dataset. | |
| Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles | cell types and tissues with high or low DNA methylation of TBX4 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at TBX4 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of TBX4 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of TBX4 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of TBX4 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
| TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of TBX4 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of TBX4 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of TBX4 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of TBX4 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with TBX4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with TBX4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
