The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TBX1  -  T-box 1

Homo sapiens

Synonyms: CAFS, CATCH22, CTHM, DGCR, DGS, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TBX1


Psychiatry related information on TBX1


High impact information on TBX1


Chemical compound and disease context of TBX1


Biological context of TBX1

  • Here we show that although TBX1, TBX2 and the Xenopus T protein (Xbra) share only 50-60% identity within their DNA-binding domains they can bind the same DNA sequence in vitro [21].
  • INTERPRETATION: Our results suggest that the TBX1 mutation is responsible for five major phenotypes in del22q11.2 syndrome [22].
  • Allelic variations at the haploid TBX1 locus do not influence the cardiac phenotype in cases of 22q11 microdeletion [23].
  • The level of BMP4 signaling is critical for the regulation of distinct T-box gene expression domains and growth along the dorso-ventral axis of the optic cup [24].
  • Members of the T-box family of transcription factors share an evolutionarily conserved DNA-binding domain and play significant roles in various processes of embryonic development [25].

Anatomical context of TBX1

  • Human and mouse studies indicate that haploinsufficiency of the transcription factor TBX1 disrupts pharyngeal arch development, resulting in the cardiac and craniofacial features associated with microdeletion of 22q11 (del22q11), the most frequent human deletion syndrome [26].
  • Expression of human TBX1 in adult and fetal tissues, as determined by Northern blot analysis, is similar to that found in the mouse [27].
  • Tbx2 and Tbx3 are closely related T-box proteins that have been implicated in development of a number of different tissues including the mammary gland [28].
  • New T-box family members have been found in vertebrate and invertebrate embryos and the importance of this gene family is illustrated by the discovery that mutations in human TBX5 are responsible for Holt-Oram syndrome, which is characterised by abnormalities in heart and forelimb development [29].
  • The role of Brachyury and other T-box genes in the differentiation of mesoderm and endoderm of vertebrates is well established [30].

Associations of TBX1 with chemical compounds

  • The T-box transcription factor T-bet is expressed in a number of hematopoetic cell types and plays an essential role in the lineage determination of Th1 T-helper cells [31].
  • Thus, we suggest that del22q11 is a contiguous gene syndrome involving dose-sensitive interaction of CRKL and TBX1 and locally aberrant RA signaling [32].
  • One mutant gene contains a single base substitution that changes a tryptophan codon (TGG) to a termination codon (TGA) [33].
  • One mutation consisted of insertion of an adenosine at position 1304 which created a premature termination codon (TAA), whereas the second consisted of deletion of the thymidine at position 1298 which created a premature termination codon (TGA) 23 nucleotides downstream [34].
  • Analysis of over 7000 nucleotides of the gene revealed a single base mutation that altered a CG dinucleotide and converted the codon CGA for arginine at amino acid position alpha 1-732 to TGA, a stop codon [35].

Regulatory relationships of TBX1


Other interactions of TBX1

  • At least seven family members are expressed in the developing mammalian heart, and the human T-box genes TBX1 and TBX5 are mutated in cardiac congenital anomaly syndromes [38].
  • COMT and TBX1 were deleted in all 44 subjects, and PRODH in 40 subjects (19 SZ, 21 NP) [39].
  • Virtual cloning and physical mapping of a human T-box gene, TBX4 [40].
  • RECENT FINDINGS: The identification of candidate genes for heart anomalies, mental illness, and other clinical phenotypes has been reported in the past year with a focus on TBX1 for cardiac and craniofacial phenotypes and COMT and PRODH for psychiatric disorders [41].
  • Truncated forms of cytosolic serine hydroxymethyl transferase (cSHMT), T-box transcription factor 3 (Tbx3) and utrophin were aberrantly expressed in samples from cancer patients as compared to samples from noncancerous cases [42].

Analytical, diagnostic and therapeutic context of TBX1

  • Sequence analysis of the proband band 3 cDNA and genomic DNA showed a C --> T substitution resulting in a nonsense mutation (CGA --> TGA; Arg --> Stop) at the position corresponding to codon 646 in human red cell band 3 cDNA [43].
  • We report the molecular cloning of human and mouse homologs of the selD gene, designated Sps2, which contains an in-frame TGA codon at a site corresponding to the enzyme's putative active site [44].
  • Polymerase chain reaction (PCR) amplification of 576 base pairs of exon h (VIII) with cloning and dideoxy sequencing of cloned DNA from one hemophiliac revealed a single C----T transition in codon 338 that changes an arginine residue codon CGA to a nonsense codon TGA [45].
  • The CATCH 22 acronym outlines the main clinical features of 22q11.2 deletions (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate and hypocalcemia), usually found in DiGeorge (DGS) and velo-cardio-facial (VCFS) syndromes [46].
  • The chemical composition of solution precursors and resultant beta-Co(OH)2 crystallites has been analyzed with UV-vis/FTIR/CHN /XRD/TGA/TEM/SAED methods [47].


  1. Developing models of DiGeorge syndrome. Epstein, J.A. Trends Genet. (2001) [Pubmed]
  2. The T-box repressors TBX2 and TBX3 specifically regulate the tumor suppressor gene p14ARF via a variant T-site in the initiator. Lingbeek, M.E., Jacobs, J.J., van Lohuizen, M. J. Biol. Chem. (2002) [Pubmed]
  3. Assessment of association between variants and haplotypes of the remaining TBX1 gene and manifestations of congenital heart defects in 22q11.2 deletion patients. Rauch, A., Devriendt, K., Koch, A., Rauch, R., Gewillig, M., Kraus, C., Weyand, M., Singer, H., Reis, A., Hofbeck, M. J. Med. Genet. (2004) [Pubmed]
  4. T-box binding protein type two (TBX2) is an immediate early gene target in retinoic-acid-treated B16 murine melanoma cells. Boskovic, G., Niles, R.M. Exp. Cell Res. (2004) [Pubmed]
  5. Tbx1 is regulated by tissue-specific forkhead proteins through a common Sonic hedgehog-responsive enhancer. Yamagishi, H., Maeda, J., Hu, T., McAnally, J., Conway, S.J., Kume, T., Meyers, E.N., Yamagishi, C., Srivastava, D. Genes Dev. (2003) [Pubmed]
  6. Disruption of the clathrin heavy chain-like gene (CLTCL) associated with features of DGS/VCFS: a balanced (21;22)(p12;q11) translocation. Holmes, S.E., Riazi, M.A., Gong, W., McDermid, H.E., Sellinger, B.T., Hua, A., Chen, F., Wang, Z., Zhang, G., Roe, B., Gonzalez, I., McDonald-McGinn, D.M., Zackai, E., Emanuel, B.S., Budarf, M.L. Hum. Mol. Genet. (1997) [Pubmed]
  7. Temporal perception in velo-cardio-facial syndrome. Debbané, M., Glaser, B., Gex-Fabry, M., Eliez, S. Neuropsychologia. (2005) [Pubmed]
  8. Association study of a promoter polymorphism of UFD1L gene with schizophrenia. De Luca, A., Pasini, A., Amati, F., Botta, A., Spalletta, G., Alimenti, S., Caccamo, F., Conti, E., Trakalo, J., Macciardi, F., Dallapiccola, B., Novelli, G. Am. J. Med. Genet. (2001) [Pubmed]
  9. A multiple case study of verbal short-term memory in velo-cardio-facial syndrome. Majerus, S., Glaser, B., Van der Linden, M., Eliez, S. Journal of intellectual disability research : JIDR. (2006) [Pubmed]
  10. Transient global amnesia: neuropsychological findings after single and multiple attacks. Gallassi, R., Stracciari, A., Morreale, A., Lorusso, S., Rebucci, G.G., Lugaresi, E. Eur. Neurol. (1993) [Pubmed]
  11. Homozygous silencing of T-box transcription factor EOMES leads to microcephaly with polymicrogyria and corpus callosum agenesis. Baala, L., Briault, S., Etchevers, H.C., Laumonnier, F., Natiq, A., Amiel, J., Boddaert, N., Picard, C., Sbiti, A., Asermouh, A., Attié-Bitach, T., Encha-Razavi, F., Munnich, A., Sefiani, A., Lyonnet, S. Nat. Genet. (2007) [Pubmed]
  12. Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation. Hiroi, Y., Kudoh, S., Monzen, K., Ikeda, Y., Yazaki, Y., Nagai, R., Komuro, I. Nat. Genet. (2001) [Pubmed]
  13. TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Merscher, S., Funke, B., Epstein, J.A., Heyer, J., Puech, A., Lu, M.M., Xavier, R.J., Demay, M.B., Russell, R.G., Factor, S., Tokooya, K., Jore, B.S., Lopez, M., Pandita, R.K., Lia, M., Carrion, D., Xu, H., Schorle, H., Kobler, J.B., Scambler, P., Wynshaw-Boris, A., Skoultchi, A.I., Morrow, B.E., Kucherlapati, R. Cell (2001) [Pubmed]
  14. The T-box transcription factor gene TBX22 is mutated in X-linked cleft palate and ankyloglossia. Braybrook, C., Doudney, K., Marçano, A.C., Arnason, A., Bjornsson, A., Patton, M.A., Goodfellow, P.J., Moore, G.E., Stanier, P. Nat. Genet. (2001) [Pubmed]
  15. Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome. Guris, D.L., Fantes, J., Tara, D., Druker, B.J., Imamoto, A. Nat. Genet. (2001) [Pubmed]
  16. T-bet, a Th1 transcription factor, is up-regulated in T cells from patients with aplastic anemia. Solomou, E.E., Keyvanfar, K., Young, N.S. Blood (2006) [Pubmed]
  17. Mistranslation of a TGA termination codon as tryptophan in recombinant platelet-derived growth factor expressed in Escherichia coli. Lu, K.V., Rohde, M.F., Thomason, A.R., Kenney, W.C., Lu, H.S. Biochem. J. (1995) [Pubmed]
  18. Dimethylsulfone as a growth substrate for novel methylotrophic species of Hyphomicrobium and Arthrobacter. Borodina, E., Kelly, D.P., Rainey, F.A., Ward-Rainey, N.L., Wood, A.P. Arch. Microbiol. (2000) [Pubmed]
  19. The in vitro hydrolysis of poly(ester urethane)s consisting of poly[(R)-3-hydroxybutyrate] and poly(ethylene glycol). Loh, X.J., Tan, K.K., Li, X., Li, J. Biomaterials (2006) [Pubmed]
  20. Enzymes of dimethylsulfone metabolism and the phylogenetic characterization of the facultative methylotrophs Arthrobacter sulfonivorans sp. nov., Arthrobacter methylotrophus sp. nov., and Hyphomicrobium sulfonivorans sp. nov. Borodina, E., Kelly, D.P., Schumann, P., Rainey, F.A., Ward-Rainey, N.L., Wood, A.P. Arch. Microbiol. (2002) [Pubmed]
  21. Differential DNA binding and transcription modulation by three T-box proteins, T, TBX1 and TBX2. Sinha, S., Abraham, S., Gronostajski, R.M., Campbell, C.E. Gene (2000) [Pubmed]
  22. Role of TBX1 in human del22q11.2 syndrome. Yagi, H., Furutani, Y., Hamada, H., Sasaki, T., Asakawa, S., Minoshima, S., Ichida, F., Joo, K., Kimura, M., Imamura, S., Kamatani, N., Momma, K., Takao, A., Nakazawa, M., Shimizu, N., Matsuoka, R. Lancet (2003) [Pubmed]
  23. Allelic variations at the haploid TBX1 locus do not influence the cardiac phenotype in cases of 22q11 microdeletion. Voelckel, M.A., Girardot, L., Giusiano, B., Levy, N., Philip, N. Ann. Genet. (2004) [Pubmed]
  24. The level of BMP4 signaling is critical for the regulation of distinct T-box gene expression domains and growth along the dorso-ventral axis of the optic cup. Behesti, H., Holt, J.K., Sowden, J.C. BMC Dev. Biol. (2006) [Pubmed]
  25. T-box genes in the ascidian Ciona intestinalis: characterization of cDNAs and spatial expression. Takatori, N., Hotta, K., Mochizuki, Y., Satoh, G., Mitani, Y., Satoh, N., Satou, Y., Takahashi, H. Dev. Dyn. (2004) [Pubmed]
  26. Tbx1 regulates fibroblast growth factors in the anterior heart field through a reinforcing autoregulatory loop involving forkhead transcription factors. Hu, T., Yamagishi, H., Maeda, J., McAnally, J., Yamagishi, C., Srivastava, D. Development (2004) [Pubmed]
  27. Isolation and characterization of a gene from the DiGeorge chromosomal region homologous to the mouse Tbx1 gene. Chieffo, C., Garvey, N., Gong, W., Roe, B., Zhang, G., Silver, L., Emanuel, B.S., Budarf, M.L. Genomics (1997) [Pubmed]
  28. The role of Tbx2 and Tbx3 in mammary development and tumorigenesis. Rowley, M., Grothey, E., Couch, F.J. Journal of mammary gland biology and neoplasia. (2004) [Pubmed]
  29. Brachyury and the T-box genes. Smith, J. Curr. Opin. Genet. Dev. (1997) [Pubmed]
  30. Brachyury, the blastopore and the evolution of the mesoderm. Technau, U. Bioessays (2001) [Pubmed]
  31. T-box proteins differentially activate the expression of the endogenous interferon gamma gene versus transfected reporter genes in non-immune cells. Butz, N.V., Gronostajski, R.M., Campbell, C.E. Gene (2006) [Pubmed]
  32. Dose-dependent interaction of Tbx1 and Crkl and locally aberrant RA signaling in a model of del22q11 syndrome. Guris, D.L., Duester, G., Papaioannou, V.E., Imamoto, A. Dev. Cell (2006) [Pubmed]
  33. Internalization-defective LDL receptors produced by genes with nonsense and frameshift mutations that truncate the cytoplasmic domain. Lehrman, M.A., Goldstein, J.L., Brown, M.S., Russell, D.W., Schneider, W.J. Cell (1985) [Pubmed]
  34. Nonsense mutations affect C1 inhibitor messenger RNA levels in patients with type I hereditary angioneurotic edema. Frangi, D., Cicardi, M., Sica, A., Colotta, F., Agostoni, A., Davis, A.E. J. Clin. Invest. (1991) [Pubmed]
  35. Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy). Ahmad, N.N., Ala-Kokko, L., Knowlton, R.G., Jimenez, S.A., Weaver, E.J., Maguire, J.I., Tasman, W., Prockop, D.J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  36. Association analysis of novel TBX21 variants with asthma phenotypes. Chung, H.T., Kim, L.H., Park, B.L., Lee, J.H., Park, H.S., Choi, B.W., Hong, S.J., Chae, S.C., Kim, J.J., Park, C.S., Shin, H.D. Hum. Mutat. (2003) [Pubmed]
  37. T-bet Binding to Newly Identified Target Gene Promoters Is Cell Type-independent but Results in Variable Context-dependent Functional Effects. Beima, K.M., Miazgowicz, M.M., Lewis, M.D., Yan, P.S., Huang, T.H., Weinmann, A.S. J. Biol. Chem. (2006) [Pubmed]
  38. T-box transcription factors and their roles in regulatory hierarchies in the developing heart. Stennard, F.A., Harvey, R.P. Development (2005) [Pubmed]
  39. Molecular characterization of deletion breakpoints in adults with 22q11 deletion syndrome. Weksberg, R., Stachon, A.C., Squire, J.A., Moldovan, L., Bayani, J., Meyn, S., Chow, E., Bassett, A.S. Hum. Genet. (2007) [Pubmed]
  40. Virtual cloning and physical mapping of a human T-box gene, TBX4. Yi, C.H., Russ, A., Brook, J.D. Genomics (2000) [Pubmed]
  41. Velo-cardio-facial syndrome. Shprintzen, R.J., Higgins, A.M., Antshel, K., Fremont, W., Roizen, N., Kates, W. Curr. Opin. Pediatr. (2005) [Pubmed]
  42. Increased expression of cSHMT, Tbx3 and utrophin in plasma of ovarian and breast cancer patients. Lomnytska, M., Dubrovska, A., Hellman, U., Volodko, N., Souchelnytskyi, S. Int. J. Cancer (2006) [Pubmed]
  43. Defective anion transport and marked spherocytosis with membrane instability caused by hereditary total deficiency of red cell band 3 in cattle due to a nonsense mutation. Inaba, M., Yawata, A., Koshino, I., Sato, K., Takeuchi, M., Takakuwa, Y., Manno, S., Yawata, Y., Kanzaki, A., Sakai, J., Ban, A., Ono, K., Maede, Y. J. Clin. Invest. (1996) [Pubmed]
  44. Identification of a novel selD homolog from eukaryotes, bacteria, and archaea: is there an autoregulatory mechanism in selenocysteine metabolism? Guimarães, M.J., Peterson, D., Vicari, A., Cocks, B.G., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Ferrick, D.A., Kastelein, R.A., Bazan, J.F., Zlotnik, A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  45. A codon 338 nonsense mutation in the factor IX gene in unrelated hemophilia B patients: factor IX338 New York. Driscoll, M.C., Bouhassira, E., Aledort, L.M. Blood (1989) [Pubmed]
  46. UFD1L, a developmentally expressed ubiquitination gene, is deleted in CATCH 22 syndrome. Pizzuti, A., Novelli, G., Ratti, A., Amati, F., Mari, A., Calabrese, G., Nicolis, S., Silani, V., Marino, B., Scarlato, G., Ottolenghi, S., Dallapiccola, B. Hum. Mol. Genet. (1997) [Pubmed]
  47. Arresting butterfly-like intermediate nanocrystals of beta-Co(OH)2 via ethylenediamine-mediated synthesis. Sampanthar, J.T., Zeng, H.C. J. Am. Chem. Soc. (2002) [Pubmed]
WikiGenes - Universities