TBX2 (T-box 2)

2005-07-01   Ayse Elif Erson , Elizabeth M. Petty 

Departments of Human Genetics and Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA (EMP)





Genes of the same T-box subfamily are thought to have arisen from duplication and recombination of a single ancestor gene. TBX2 is most closely related to TBX3 (12q24), whereas the other members of the subfamily, TBX4 and TBX5, are more closely related to one another. It is postulated that genes of the same subfamily may have redundant expression patterns and thus potential functional redundancy.
Atlas Image
The alignment of TBX2 mRNA (3396 bp) to its genomic sequence.


TBX2 gene spans 9,5kb. TBX2 gene has 7 exons and the sizes of the exons 1 to 7 are 676, 268, 147, 77, 164, 635, 1413 bps. Exon/intron boundaries of TBX2 and a polymorphism within intron 2 of the gene have also been reported.


TBX2 mRNA is 3396 bp. TBX2 mRNA is expressed in a wide variety of tissues including fetal kidney and fetal lung as well as multiple adult tissues, kidney, lung, placenta, ovary, prostate, spleen, testis and breast. Relatively reduced expression of TBX2 can be detected in heart, white blood cells, small intestine and thymus. Transcript size heterogeneity has been detected for TBX2, possibly due to alternative polyadenylation.
Increased TBX2 mRNA is observed within 2 hours after addition of retinoic acid in B16 mouse melanoma cells due to the presence of a degenerate retinoic acid response element (RARE) between -186 and -163 in the promoter region of the TBX2 gene.

Transcript localisation: Human and mouse TBX2, TBX3, and TBX5 transcripts detected by riboprobes are found asymmetrically across the embryonic neural retina, with highest levels of transcripts within dorsal and peripheral retina. The dorsoventral gradient of TBX2 expression cannot be detected before the ganglion cell layer (GCL) forms and expression is found to be restricted to the inner neuroblastic retina and later to the GCL and inner nuclear layer.
TBX2 transcript is also detected in the optic and otic vesicles at 9.5 dpc, and in the naso-facial mesenchyme, and later in the developing limbs and other internal organ primordia (of lungs and genitalia).
Later at around 8 and 10 dpc, TBX2 is detected in allantois, inflow tract (IFT), outflow tract (OFT) and atrio-ventricular canal (AVC) of the developing mouse heart. Chick heart development is also consistent in terms of similar TBX2 expression patterns.
During mammary development, TBX2 expression is detected at 11.5 dpc in the mesodermal milk lines.


No pseudogenes have been reported for TBX2.



Protein consists of 702 amino acids and is 74.2 kDa. Protein has the T-box DNA binding domain (corresponds to amino acids 96-279) of the T-box family of transcriptional regulators.


In an evolutionarily diverse group of organisms including chick, Xenopus, mouse, and human, TBX2 is involved during development of widely diverse organs and tissues including limbs, kidneys, lungs, mammary glands, heart and craniofacial structures.
In order to identify genes that may be regulated by Tbx2, mouse cDNA microarrays were used to analyze differential gene expression profiles, comparing stably transfected NIH3T3 cells overexpressing Tbx2 with vector-transfected controls. 107 genes were up-regulated (more than or equal to 2-fold) and 66 genes were down-regulated (more than or equal to 2-fold). Among the upregulated genes in the Tbx2-overexpressing cells were: Caveolin, Pleiotrophin, Osteoblast-specific factor-2 and Collagen Type I alpha. Cadherin 3, Tenascin C, and Insulin-like Growth Factor Binding Protein 10/CYR61 (IBP10) were among the genes that are downregulated.
In vitro reporter assays and transgenic mice studies suggest that TBX2 represses the transcription of certain cardiac genes (e.g. Connexin 40, Connexin 43, and Natriuretic Peptide Precursor A) during heart development. TBX2 and TBX3 are also thought to be regulating one another in Hedgehog related signaling pathways during chick limb development.
In addition to developmental functions, evidence suggest that TBX2 also has important roles in cell cycle regulation through repressing the expression of CDKN1A (p21, cyclin-dependent kinase inhibitor) and CDKN2A (p19ARF). In BMI oncogene deficient murine embryonic fibroblasts, TBX2 is shown to repress the CDKN2A promoter and also attenuate the induction of CDKN2A by E2F1, MYC, and HRAS, providing senescence bypass and suggesting TBX2 as a potent immortalizing gene.


C.familiaris: Tbx2, T-box 2 transcription factor
M.musculus: Tbx2, T-box 2
R.norvegicus: Tbx2_predicted, T-box 2 (predicted)
D.melanogaster: bi, bifid
A.gambiae: 1280927, Anopheles gambiae str. PEST ENSANGG00000011542 gene.
C.elegans: tbx-2, T-box family member (47.0 kD)



Despite the high frequency T-box family gene mutations identified as causes of congenital developmental disorders, there have been no mutations reported for TBX2 that cause congenital anomalies. Germline segregation of TBX2 mutations with human diseases has not been identified.


CGH (comparative genomic hybridization), Southern blot, FISH, PCR based techniques and microarray analyses suggest amplification and overexpression of TBX2 in certain cancer cells.

Implicated in

Entity name
Breast cancer
TBX2 has been found to be amplified and overexpressed in breast cancer cell lines and primary tumors. TBX2 resides on the chromosomal band 17q23 that is frequently amplified in breast cancer cells. Evidence suggests presence of distinct proximal and distal amplicons on 17q23 with defined boundaries. TBX2 seems to be at the center of the distal amplicon. In addition to breast cancer cell line data, a study of tissue microarray of 372 primary tumors found TBX2 amplification in 8.6% of the cases. Moreover, preferential amplification and overexpression of TBX2 have been detected in BRCA1 and BRCA2 mutated breast tumors compared to sporadic controls.
Entity name
Pancreatic Cancer
TBX2 amplification has been detected in 50% of 20 pancreatic cancer cell lines detected by interphase FISH.
Entity name
TBX2 overexpression in melanoma cell lines is thought to target histone deacetylase 1 to the CDKN1A initiator. Expression of a dominant-negative Tbx2 leads to displacement of histone deacetylase 1 with up-regulation of CDKN1A expression, and the induction of replicative senescence in CDKN2A-null B16 melanoma cells. In human melanoma cells, expression of the same dominant negative TBX2 results with reduced growth and induction of senescence-associated heterochromatin foci.


Pubmed IDLast YearTitleAuthors
110340672000Multiple genes at 17q23 undergo amplification and overexpression in breast cancer.Bärlund M et al
145951872003Tension-induced reduction in connexin 43 expression in cranial sutures is linked to transcriptional regulation by TBX2.Borke JL et al
150937292004T-box binding protein type two (TBX2) is an immediate early gene target in retinoic-acid-treated B16 murine melanoma cells.Boskovic G et al
85300341995Cloning and mapping of a human gene (TBX2) sharing a highly conserved protein motif with the Drosophila omb gene.Campbell C et al
94349491998Genomic structure of TBX2 indicates conservation with distantly related T-box genes.Campbell CE et al
88539871996Expression of the T-box family genes, Tbx1-Tbx5, during early mouse development.Chapman DL et al
113778192001Microarray analysis of Tbx2-directed gene expression: a possible role in osteogenesis.Chen J et al
153548642004Tbx2 represses expression of Connexin43 in osteoblastic-like cells.Chen JR et al
150427002004T-box transcription factor Tbx2 represses differentiation and formation of the cardiac chambers.Christoffels VM et al
117740342001Overexpressed genes/ESTs and characterization of distinct amplicons on 17q23 in breast cancer cells.Erson AE et al
96515161998Expression of T-box genes Tbx2-Tbx5 during chick organogenesis.Gibson-Brown JJ et al
120233022002Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation.Habets PE et al
85976361995Identification, characterization, and localization to chromosome 17q21-22 of the human TBX2 homolog, member of a conserved developmental gene family.Law DJ et al
123785292002Frequent amplification of 8q24, 11q, 17q, and 20q-specific genes in pancreatic cancer.Mahlamäki EH et al
126685952003T-box genes in human disorders.Packham EA et al
155806132005T-box genes and heart development: putting the "T" in heart.Plageman TF Jr et al
149967262004Tbx2 directly represses the expression of the p21(WAF1) cyclin-dependent kinase inhibitor.Prince S et al
114835872001Virtual genome scan: a tool for restriction landmark-based scanning of the human genome.Rouillard JM et al
153000072004The role of Tbx2 and Tbx3 in mammary development and tumorigenesis.Rowley M et al
120972572002TBX2 is preferentially amplified in BRCA1- and BRCA2-related breast tumors.Sinclair CS et al
117266082001Expression of Drosophila omb-related T-box genes in the developing human and mouse neural retina.Sowden JC et al
158434142005Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation.Stennard FA et al
147238462004Tbx Genes Specify Posterior Digit Identity through Shh and BMP Signaling.Suzuki T et al
157816392005Tbx2 is overexpressed and plays an important role in maintaining proliferation and suppression of senescence in melanomas.Vance KW et al
120933832002The T-box family.Wilson V et al
110876292000Expression of chick Tbx-2, Tbx-3, and Tbx-5 genes during early heart development: evidence for BMP2 induction of Tbx2.Yamada M et al

Other Information

Locus ID:

NCBI: 6909
MIM: 600747
HGNC: 11597
Ensembl: ENSG00000121068


dbSNP: 6909
ClinVar: 6909
TCGA: ENSG00000121068


Gene IDTranscript IDUniprot

Expression (GTEx)


Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs


Pubmed IDYearTitleCitations
157816392005Tbx2 is overexpressed and plays an important role in maintaining proliferation and suppression of senescence in melanomas.84
188295432008Tbx3 represses E-cadherin expression and enhances melanoma invasiveness.61
120007492002The T-box repressors TBX2 and TBX3 specifically regulate the tumor suppressor gene p14ARF via a variant T-site in the initiator.52
192660772009Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966.48
199605412010The T-box transcription factor Tbx2: its role in development and possible implication in cancer.42
222849682012Genome-wide analysis of CpG island methylation in bladder cancer identified TBX2, TBX3, GATA2, and ZIC4 as pTa-specific prognostic markers.37
203489482010T-box 2 represses NDRG1 through an EGR1-dependent mechanism to drive the proliferation of breast cancer cells.32
228444642012The T box transcription factor TBX2 promotes epithelial-mesenchymal transition and invasion of normal and malignant breast epithelial cells.26
205348142010The retinoblastoma protein modulates Tbx2 functional specificity.22
194532612009High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men.20


Ayse Elif Erson ; Elizabeth M. Petty

TBX2 (T-box 2)

Atlas Genet Cytogenet Oncol Haematol. 2005-07-01

Online version: http://atlasgeneticsoncology.org/gene/42485/tbx2id42485ch17q23