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Structural highlights

Disease

[TBX5_HUMAN] Holt-Oram syndrome. The disease is caused by mutations affecting the gene represented in this entry. Defects in TBX5 are associated with susceptibility to dilated cardiomyopathy (DCM). A disorder characterized by ventricular and impaired systolic function, resulting in heart failure and arrhythmia. Patient are at risk of premature death.^{[1] [2]} [NKX25_HUMAN] Athyreosis;Familial isolated congenital asplenia;Atrial septal defect - atrioventricular conduction defects;Atrial septal defect, ostium secundum type;Hypoplastic left heart syndrome;Tetralogy of Fallot;Familial atrial fibrillation;Familial progressive cardiac conduction defect;Thyroid hypoplasia;Ventricular septal defect. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

[TBX5_HUMAN] DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation.^{[3] [4] [5]} [NKX25_HUMAN] Implicated in commitment to and/or differentiation of the myocardial lineage. Acts as a transcriptional activator of ANF in cooperation with GATA4 (By similarity). It is transcriptionally controlled by PBX1 and acts as a transcriptional repressor of CDKN2B (By similarity). It is required for spleen development.^[6]

References

1. ↑ Zhang XL, Qiu XB, Yuan F, Wang J, Zhao CM, Li RG, Xu L, Xu YJ, Shi HY, Hou XM, Qu XK, Xu YW, Yang YQ. TBX5 loss-of-function mutation contributes to familial dilated cardiomyopathy. Biochem Biophys Res Commun. 2015 Mar 27;459(1):166-71. doi:, 10.1016/j.bbrc.2015.02.094. Epub 2015 Feb 26. PMID:25725155 doi:http://dx.doi.org/10.1016/j.bbrc.2015.02.094
2. ↑ Zhou W, Zhao L, Jiang JQ, Jiang WF, Yang YQ, Qiu XB. A novel TBX5 loss-of-function mutation associated with sporadic dilated cardiomyopathy. Int J Mol Med. 2015 Jul;36(1):282-8. doi: 10.3892/ijmm.2015.2206. Epub 2015 May, 11. PMID:25963046 doi:http://dx.doi.org/10.3892/ijmm.2015.2206
3. ↑ Zhang XL, Qiu XB, Yuan F, Wang J, Zhao CM, Li RG, Xu L, Xu YJ, Shi HY, Hou XM, Qu XK, Xu YW, Yang YQ. TBX5 loss-of-function mutation contributes to familial dilated cardiomyopathy. Biochem Biophys Res Commun. 2015 Mar 27;459(1):166-71. doi:, 10.1016/j.bbrc.2015.02.094. Epub 2015 Feb 26. PMID:25725155 doi:http://dx.doi.org/10.1016/j.bbrc.2015.02.094
4. ↑ Zhou W, Zhao L, Jiang JQ, Jiang WF, Yang YQ, Qiu XB. A novel TBX5 loss-of-function mutation associated with sporadic dilated cardiomyopathy. Int J Mol Med. 2015 Jul;36(1):282-8. doi: 10.3892/ijmm.2015.2206. Epub 2015 May, 11. PMID:25963046 doi:http://dx.doi.org/10.3892/ijmm.2015.2206
5. ↑ Li QY, Newbury-Ecob RA, Terrett JA, Wilson DI, Curtis AR, Yi CH, Gebuhr T, Bullen PJ, Robson SC, Strachan T, Bonnet D, Lyonnet S, Young ID, Raeburn JA, Buckler AJ, Law DJ, Brook JD. Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nat Genet. 1997 Jan;15(1):21-9. PMID:8988164 doi:http://dx.doi.org/10.1038/ng0197-21
6. ↑ Koss M, Bolze A, Brendolan A, Saggese M, Capellini TD, Bojilova E, Boisson B, Prall OW, Elliott DA, Solloway M, Lenti E, Hidaka C, Chang CP, Mahlaoui N, Harvey RP, Casanova JL, Selleri L. Congenital asplenia in mice and humans with mutations in a Pbx/Nkx2-5/p15 module. Dev Cell. 2012 May 15;22(5):913-26. doi: 10.1016/j.devcel.2012.02.009. Epub 2012 , May 3. PMID:22560297 doi:http://dx.doi.org/10.1016/j.devcel.2012.02.009