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TBX2 (T-box 2)

Written2005-07Ayse Elif Erson, Elizabeth M. Petty
Departments of Human Genetics and Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA (EMP)

(Note : for Links provided by Atlas : click)


Alias_namesT-box 2
Other aliasFLJ10169
HGNC (Hugo) TBX2
LocusID (NCBI) 6909
Atlas_Id 42485
Location 17q23.2  [Link to chromosome band 17q23]
Location_base_pair Starts at 61399896 and ends at 61409466 bp from pter ( according to hg19-Feb_2009)  [Mapping TBX2.png]
Local_order Genes flanking TBX2 in centromere to telomere direction on 17q23 are:
APPBP2, 17q21-q23, amyloid beta precursor protein (cytoplasmic tail) binding protein 2
TBX2, 17q23, T-box2
PPM1D, 17q23, protein phosphatase 1D magnesium-dependent, delta isoform
LOC440450, 17q23.2 LOC440450
LOC388407, 17q23.2, hypothetical gene supported by BC046200
LOC388406, 17q23.2, hypothetical LOC388406
MGC71999, 17q23.2, alpha-NAC protein
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CPD (17q11.2) / TBX2 (17q23.2)
Note T-box proteins contain a T-domain that has roles in dimerization and DNA binding. TBX2 belongs to the Tbx2 subfamily of T-box transcription factors. Other subfamilies of T-box genes are Brachyury, T-brain1, Tbx1 and Tbx6. TBX2, TBX3, TBX4 and TBX5 belong to the Tbx2 subfamily. TBX2 and TBX3 are the only mammalian T-box factors with reported transcriptional repressor functions.


Note 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.
  The alignment of TBX2 mRNA (3396 bp) to its genomic sequence.
Description 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.
Transcription 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.

Pseudogene No pseudogenes have been reported for TBX2.


Description 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.
Function 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.
Homology 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)


Germinal 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.
Somatic 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 Breast cancer
Note 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 Pancreatic Cancer
Note TBX2 amplification has been detected in 50% of 20 pancreatic cancer cell lines detected by interphase FISH.
Entity Melanomas
Note 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.
Note Analysis of TBX2 in other tumor types has not been widely reported.


Multiple genes at 17q23 undergo amplification and overexpression in breast cancer.
Bärlund M, Monni O, Kononen J, Cornelison R, Torhorst J, Sauter G, Kallioniemi OLLI-P, Kallioniemi A
Cancer research. 2000 ; 60 (19) : 5340-5344.
PMID 11034067
Tension-induced reduction in connexin 43 expression in cranial sutures is linked to transcriptional regulation by TBX2.
Borke JL, Yu JC, Isales CM, Wagle N, Do NN, Chen JR, Bollag RJ
Annals of plastic surgery. 2003 ; 51 (5) : 499-504.
PMID 14595187
T-box binding protein type two (TBX2) is an immediate early gene target in retinoic-acid-treated B16 murine melanoma cells.
Boskovic G, Niles RM
Experimental cell research. 2004 ; 295 (2) : 281-289.
PMID 15093729
Cloning and mapping of a human gene (TBX2) sharing a highly conserved protein motif with the Drosophila omb gene.
Campbell C, Goodrich K, Casey G, Beatty B
Genomics. 1995 ; 28 (2) : 255-260.
PMID 8530034
Genomic structure of TBX2 indicates conservation with distantly related T-box genes.
Campbell CE, Casey G, Goodrich K
Mammalian genome : official journal of the International Mammalian Genome Society. 1998 ; 9 (1) : 70-73.
PMID 9434949
Expression of the T-box family genes, Tbx1-Tbx5, during early mouse development.
Chapman DL, Garvey N, Hancock S, Alexiou M, Agulnik SI, Gibson-Brown JJ, Cebra-Thomas J, Bollag RJ, Silver LM, Papaioannou VE
Developmental dynamics : an official publication of the American Association of Anatomists. 1996 ; 206 (4) : 379-390.
PMID 8853987
Microarray analysis of Tbx2-directed gene expression: a possible role in osteogenesis.
Chen J, Zhong Q, Wang J, Cameron RS, Borke JL, Isales CM, Bollag RJ
Molecular and cellular endocrinology. 2001 ; 177 (1-2) : 43-54.
PMID 11377819
Tbx2 represses expression of Connexin43 in osteoblastic-like cells.
Chen JR, Chatterjee B, Meyer R, Yu JC, Borke JL, Isales CM, Kirby ML, Lo CW, Bollag RJ
Calcified tissue international. 2004 ; 74 (6) : 561-573.
PMID 15354864
T-box transcription factor Tbx2 represses differentiation and formation of the cardiac chambers.
Christoffels VM, Hoogaars WM, Tessari A, Clout DE, Moorman AF, Campione M
Developmental dynamics : an official publication of the American Association of Anatomists. 2004 ; 229 (4) : 763-770.
PMID 15042700
Overexpressed genes/ESTs and characterization of distinct amplicons on 17q23 in breast cancer cells.
Erson AE, Niell BL, DeMers SK, Rouillard JM, Hanash SM, Petty EM
Neoplasia (New York, N.Y.). 2001 ; 3 (6) : 521-526.
PMID 11774034
Expression of T-box genes Tbx2-Tbx5 during chick organogenesis.
Gibson-Brown JJ, I Agulnik S, Silver LM, Papaioannou VE
Mechanisms of development. 1998 ; 74 (1-2) : 165-169.
PMID 9651516
Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation.
Habets PE, Moorman AF, Clout DE, van Roon MA, Lingbeek M, van Lohuizen M, Campione M, Christoffels VM
Genes & development. 2002 ; 16 (10) : 1234-1246.
PMID 12023302
Identification, characterization, and localization to chromosome 17q21-22 of the human TBX2 homolog, member of a conserved developmental gene family.
Law DJ, Gebuhr T, Garvey N, Agulnik SI, Silver LM
Mammalian genome : official journal of the International Mammalian Genome Society. 1995 ; 6 (11) : 793-797.
PMID 8597636
Frequent amplification of 8q24, 11q, 17q, and 20q-specific genes in pancreatic cancer.
Mahlamäki EH, Bärlund M, Tanner M, Gorunova L, Höglund M, Karhu R, Kallioniemi A
Genes, chromosomes & cancer. 2002 ; 35 (4) : 353-358.
PMID 12378529
T-box genes in human disorders.
Packham EA, Brook JD
Human molecular genetics. 2003 ; 12 Spec No 1 : R37-R44.
PMID 12668595
T-box genes and heart development: putting the T in heart.
Plageman TF Jr, Yutzey KE
Developmental dynamics : an official publication of the American Association of Anatomists. 2005 ; 232 (1) : 11-20.
PMID 15580613
Tbx2 directly represses the expression of the p21(WAF1) cyclin-dependent kinase inhibitor.
Prince S, Carreira S, Vance KW, Abrahams A, Goding CR
Cancer research. 2004 ; 64 (5) : 1669-1674.
PMID 14996726
Virtual genome scan: a tool for restriction landmark-based scanning of the human genome.
Rouillard JM, Erson AE, Kuick R, Asakawa J, Wimmer K, Muleris M, Petty EM, Hanash S
Genome research. 2001 ; 11 (8) : 1453-1459.
PMID 11483587
The role of Tbx2 and Tbx3 in mammary development and tumorigenesis.
Rowley M, Grothey E, Couch FJ
Journal of mammary gland biology and neoplasia. 2004 ; 9 (2) : 109-118.
PMID 15300007
TBX2 is preferentially amplified in BRCA1- and BRCA2-related breast tumors.
Sinclair CS, Adem C, Naderi A, Soderberg CL, Johnson M, Wu K, Wadum L, Couch VL, Sellers TA, Schaid D, Slezak J, Fredericksen Z, Ingle JN, Hartmann L, Jenkins RB, Couch FJ
Cancer research. 2002 ; 62 (13) : 3587-3591.
PMID 12097257
Expression of Drosophila omb-related T-box genes in the developing human and mouse neural retina.
Sowden JC, Holt JK, Meins M, Smith HK, Bhattacharya SS
Investigative ophthalmology & visual science. 2001 ; 42 (13) : 3095-3102.
PMID 11726608
Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation.
Stennard FA, Costa MW, Lai D, Biben C, Furtado MB, Solloway MJ, McCulley DJ, Leimena C, Preis JI, Dunwoodie SL, Elliott DE, Prall OW, Black BL, Fatkin D, Harvey RP
Development (Cambridge, England). 2005 ; 132 (10) : 2451-2462.
PMID 15843414
Tbx Genes Specify Posterior Digit Identity through Shh and BMP Signaling.
Suzuki T, Takeuchi J, Koshiba-Takeuchi K, Ogura T
Developmental cell. 2004 ; 6 (1) : 43-53.
PMID 14723846
Tbx2 is overexpressed and plays an important role in maintaining proliferation and suppression of senescence in melanomas.
Vance KW, Carreira S, Brosch G, Goding CR
Cancer research. 2005 ; 65 (6) : 2260-2268.
PMID 15781639
The T-box family.
Wilson V, Conlon FL
Genome biology. 2002 ; 3 (6) : page REVIEWS3008.
PMID 12093383
Expression of chick Tbx-2, Tbx-3, and Tbx-5 genes during early heart development: evidence for BMP2 induction of Tbx2.
Yamada M, Revelli JP, Eichele G, Barron M, Schwartz RJ
Developmental biology. 2000 ; 228 (1) : 95-105.
PMID 11087629


This paper should be referenced as such :
Erson, AE ; Petty, EM
TBX2 (T-box 2)
Atlas Genet Cytogenet Oncol Haematol. 2005;9(4):300-302.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]

Solid Tumors TT_t1717q11q23ID102473

External links

HGNC (Hugo)TBX2   11597
Entrez_Gene (NCBI)TBX2  6909  T-box transcription factor 2
GeneCards (Weizmann)TBX2
Ensembl hg19 (Hinxton)ENSG00000121068 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000121068 [Gene_View]  ENSG00000121068 [Sequence]  chr17:61399896-61409466 [Contig_View]  TBX2 [Vega]
ICGC DataPortalENSG00000121068
TCGA cBioPortalTBX2
AceView (NCBI)TBX2
Genatlas (Paris)TBX2
SOURCE (Princeton)TBX2
Genetics Home Reference (NIH)TBX2
Genomic and cartography
GoldenPath hg38 (UCSC)TBX2  -     chr17:61399896-61409466 +  17q23.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TBX2  -     17q23.2   [Description]    (hg19-Feb_2009)
GoldenPathTBX2 - 17q23.2 [CytoView hg19]  TBX2 - 17q23.2 [CytoView hg38]
Mapping of homologs : NCBITBX2 [Mapview hg19]  TBX2 [Mapview hg38]
OMIM600747   618223   
Gene and transcription
Genbank (Entrez)AB209378 AK001031 AK127429 AL832900 AW006595
RefSeq transcript (Entrez)NM_005994
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)TBX2
Alternative Splicing GalleryENSG00000121068
Gene ExpressionTBX2 [ NCBI-GEO ]   TBX2 [ EBI - ARRAY_EXPRESS ]   TBX2 [ SEEK ]   TBX2 [ MEM ]
Gene Expression Viewer (FireBrowse)TBX2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)6909
GTEX Portal (Tissue expression)TBX2
Human Protein AtlasENSG00000121068-TBX2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)TBX2
DMDM Disease mutations6909
Blocks (Seattle)TBX2
Human Protein Atlas [tissue]ENSG00000121068-TBX2 [tissue]
IPIIPI00940256   IPI00555938   IPI00956369   IPI00925935   
Protein Interaction databases
Ontologies - Pathways
Huge Navigator TBX2 [HugePedia]
snp3D : Map Gene to Disease6909
BioCentury BCIQTBX2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6909
Chemical/Pharm GKB GenePA36360
Clinical trialTBX2
canSAR (ICR)TBX2 (select the gene name)
DataMed IndexTBX2
PubMed69 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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