Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT70PISV)

DOT Name T-box transcription factor TBX5 (TBX5)
Synonyms T-box protein 5
Gene Name TBX5
Related Disease
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Holt-Oram syndrome ( )
Arthritis ( )
Atrial fibrillation ( )
Atrial septal defect ( )
Atrioventricular block ( )
Barrett esophagus ( )
Bone osteosarcoma ( )
Cardiac disease ( )
Colon cancer ( )
Colon carcinoma ( )
Colonic neoplasm ( )
Colorectal carcinoma ( )
Congenital deformities of limbs ( )
Depression ( )
Dilated cardiomyopathy ( )
Dilated cardiomyopathy 1A ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Hepatocellular carcinoma ( )
High blood pressure ( )
Lung adenocarcinoma ( )
Myocardial infarction ( )
Neoplasm ( )
Neuroblastoma ( )
Osteoarthritis ( )
Osteosarcoma ( )
Patent ductus arteriosus ( )
Polydactyly ( )
Retinoblastoma ( )
Rheumatoid arthritis ( )
Familial atrial fibrillation ( )
Heart arrhythmia ( )
Prostate cancer ( )
Prostate carcinoma ( )
Small-cell lung cancer ( )
Carcinoma of esophagus ( )
Acute myocardial infarction ( )
Advanced cancer ( )
Aortic valve disease 2 ( )
Arrhythmia ( )
Congenital heart disease ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Heart septal defect ( )
Non-small-cell lung cancer ( )
UniProt ID
TBX5_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2X6U; 2X6V; 4S0H; 5BQD
Pfam ID
PF00907
Sequence
MADADEGFGLAHTPLEPDAKDLPCDSKPESALGAPSKSPSSPQAAFTQQGMEGIKVFLHE
RELWLKFHEVGTEMIITKAGRRMFPSYKVKVTGLNPKTKYILLMDIVPADDHRYKFADNK
WSVTGKAEPAMPGRLYVHPDSPATGAHWMRQLVSFQKLKLTNNHLDPFGHIILNSMHKYQ
PRLHIVKADENNGFGSKNTAFCTHVFPETAFIAVTSYQNHKITQLKIENNPFAKGFRGSD
DMELHRMSRMQSKEYPVVPRSTVRQKVASNHSPFSSESRALSTSSNLGSQYQCENGVSGP
SQDLLPPPNPYPLPQEHSQIYHCTKRKEEECSTTDHPYKKPYMETSPSEEDSFYRSSYPQ
QQGLGASYRTESAQRQACMYASSAPPSEPVPSLEDISCNTWPSMPSYSSCTVTTVQPMDR
LPYQHFSAHFTSGPLVPRLAGMANHGSPQLGEGMFQHQTSVAHQPVVRQCGPQTGLQSPG
TLQPPEFLYSHGVPRTLSPHQYHSVHGVGMVPEWSDNS
Function DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation. Binds to the core DNA motif of NPPA promoter.
Reactome Pathway
Physiological factors (R-HSA-5578768 )
Cardiogenesis (R-HSA-9733709 )
YAP1- and WWTR1 (TAZ)-stimulated gene expression (R-HSA-2032785 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bladder cancer DISUHNM0 Definitive Biomarker [1]
Breast cancer DIS7DPX1 Definitive Genetic Variation [2]
Breast carcinoma DIS2UE88 Definitive Genetic Variation [2]
Holt-Oram syndrome DISBNDZ2 Definitive Autosomal dominant [3]
Arthritis DIST1YEL Strong Biomarker [4]
Atrial fibrillation DIS15W6U Strong Biomarker [5]
Atrial septal defect DISJT76B Strong Biomarker [6]
Atrioventricular block DIS8YLE6 Strong Genetic Variation [7]
Barrett esophagus DIS416Y7 Strong Genetic Variation [8]
Bone osteosarcoma DIST1004 Strong Biomarker [9]
Cardiac disease DISVO1I5 Strong Biomarker [10]
Colon cancer DISVC52G Strong Biomarker [11]
Colon carcinoma DISJYKUO Strong Biomarker [11]
Colonic neoplasm DISSZ04P Strong Posttranslational Modification [11]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [12]
Congenital deformities of limbs DISP4N1Q Strong Genetic Variation [13]
Depression DIS3XJ69 Strong Altered Expression [4]
Dilated cardiomyopathy DISX608J Strong Biomarker [14]
Dilated cardiomyopathy 1A DIS0RK9Z Strong Altered Expression [14]
Endometrial cancer DISW0LMR Strong Biomarker [15]
Endometrial carcinoma DISXR5CY Strong Biomarker [15]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [16]
High blood pressure DISY2OHH Strong Biomarker [17]
Lung adenocarcinoma DISD51WR Strong Genetic Variation [18]
Myocardial infarction DIS655KI Strong Biomarker [19]
Neoplasm DISZKGEW Strong Biomarker [20]
Neuroblastoma DISVZBI4 Strong Biomarker [21]
Osteoarthritis DIS05URM Strong Biomarker [22]
Osteosarcoma DISLQ7E2 Strong Biomarker [9]
Patent ductus arteriosus DIS9P8YS Strong Genetic Variation [23]
Polydactyly DIS25BMZ Strong Biomarker [24]
Retinoblastoma DISVPNPB Strong Biomarker [25]
Rheumatoid arthritis DISTSB4J Strong Biomarker [26]
Familial atrial fibrillation DISL4AGF moderate Biomarker [27]
Heart arrhythmia DISLKUNL Moderate Autosomal dominant [28]
Prostate cancer DISF190Y moderate Biomarker [29]
Prostate carcinoma DISMJPLE moderate Biomarker [29]
Small-cell lung cancer DISK3LZD moderate Altered Expression [30]
Carcinoma of esophagus DISS6G4D Disputed Biomarker [31]
Acute myocardial infarction DISE3HTG Limited Genetic Variation [32]
Advanced cancer DISAT1Z9 Limited Biomarker [33]
Aortic valve disease 2 DISOMB0X Limited CausalMutation [34]
Arrhythmia DISFF2NI Limited Genetic Variation [35]
Congenital heart disease DISQBA23 Limited Genetic Variation [23]
Coronary atherosclerosis DISKNDYU Limited Genetic Variation [10]
Coronary heart disease DIS5OIP1 Limited Altered Expression [32]
Heart septal defect DISQ5C5J Limited Genetic Variation [23]
Non-small-cell lung cancer DIS5Y6R9 Limited Genetic Variation [36]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of T-box transcription factor TBX5 (TBX5). [37]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of T-box transcription factor TBX5 (TBX5). [39]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of T-box transcription factor TBX5 (TBX5). [41]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of T-box transcription factor TBX5 (TBX5). [38]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of T-box transcription factor TBX5 (TBX5). [40]
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References

1 Expression of type-IV collagenases in human tumor cell lines that can form liver colonies in chick embryos.Int J Cancer. 1994 Jan 2;56(1):46-51. doi: 10.1002/ijc.2910560109.
2 In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci.Mamm Genome. 2015 Feb;26(1-2):57-79. doi: 10.1007/s00335-014-9551-x. Epub 2015 Jan 1.
3 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
4 Down-regulation of miR-10a-5p in synoviocytes contributes to TBX5-controlled joint inflammation.J Cell Mol Med. 2018 Jan;22(1):241-250. doi: 10.1111/jcmm.13312. Epub 2017 Aug 7.
5 A calcium transport mechanism for atrial fibrillation in Tbx5-mutant mice.Elife. 2019 Mar 21;8:e41814. doi: 10.7554/eLife.41814.
6 Morphogenesis and molecular considerations on congenital cardiac septal defects.Ann Med. 2014 Dec;46(8):640-52. doi: 10.3109/07853890.2014.959557. Epub 2014 Oct 13.
7 SNP rs3825214 in TBX5 is associated with lone atrial fibrillation in Chinese Han population.PLoS One. 2013 May 24;8(5):e64966. doi: 10.1371/journal.pone.0064966. Print 2013.
8 The Barrett-associated variants at GDF7 and TBX5 also increase esophageal adenocarcinoma risk.Cancer Med. 2016 May;5(5):888-91. doi: 10.1002/cam4.641. Epub 2016 Jan 18.
9 Inhibitory Effects of Indomethacin in Human MNNG/HOS Osteosarcoma Cell Line InVitro.Cancer Invest. 2020 Jan;38(1):23-36. doi: 10.1080/07357907.2019.1698592. Epub 2019 Dec 16.
10 A HAND to TBX5 Explains the Link Between Thalidomide and Cardiac Diseases.Sci Rep. 2017 May 3;7(1):1416. doi: 10.1038/s41598-017-01641-3.
11 Epigenetic inactivation of T-box transcription factor 5, a novel tumor suppressor gene, is associated with colon cancer.Oncogene. 2010 Dec 9;29(49):6464-74. doi: 10.1038/onc.2010.370. Epub 2010 Aug 30.
12 Wnt, RSPO and Hippo Signalling in the Intestine and Intestinal Stem Cells.Genes (Basel). 2018 Jan 8;9(1):20. doi: 10.3390/genes9010020.
13 Structural basis of TBX5-DNA recognition: the T-box domain in its DNA-bound and -unbound form.J Mol Biol. 2010 Jul 2;400(1):71-81. doi: 10.1016/j.jmb.2010.04.052. Epub 2010 May 5.
14 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.
15 Combined genetic mutations and DNA-methylated genes as biomarkers for endometrial cancer detection from cervical scrapings.Clin Epigenetics. 2019 Nov 28;11(1):170. doi: 10.1186/s13148-019-0765-3.
16 c-MET and HGF mRNA expression in hepatocellular carcinoma: correlation with clinicopathological features and survival.Anticancer Res. 2013 Aug;33(8):3241-5.
17 Genome-wide association study of blood pressure and hypertension.Nat Genet. 2009 Jun;41(6):677-87. doi: 10.1038/ng.384. Epub 2009 May 10.
18 Multiplex Diagnosis of Oncogenic Fusion and MET Exon Skipping by Molecular Counting Using Formalin-Fixed Paraffin Embedded Lung Adenocarcinoma Tissues.J Thorac Oncol. 2016 Feb;11(2):203-12. doi: 10.1016/j.jtho.2015.10.005. Epub 2015 Dec 19.
19 Key Regulators of Cardiovascular Differentiation and Regeneration: Harnessing the Potential of Direct Reprogramming to Treat Heart Failure.J Card Fail. 2020 Jan;26(1):80-84. doi: 10.1016/j.cardfail.2019.09.005. Epub 2019 Sep 18.
20 A novel peptide targets CD105 for tumour imaging invivo.Oncol Rep. 2018 Nov;40(5):2935-2943. doi: 10.3892/or.2018.6643. Epub 2018 Aug 14.
21 Double-deleted vaccinia virus in virotherapy for refractory and metastatic pediatric solid tumors.Mol Oncol. 2013 Oct;7(5):944-54. doi: 10.1016/j.molonc.2013.05.004. Epub 2013 Jun 14.
22 Analysis of methylation datasets identified significantly changed genes and functional pathways in osteoarthritis.Clin Rheumatol. 2019 Dec;38(12):3529-3538. doi: 10.1007/s10067-019-04700-4. Epub 2019 Aug 2.
23 Association of NKX2-5, GATA4, and TBX5 polymorphisms with congenital heart disease in Egyptian children.Mol Genet Genomic Med. 2019 May;7(5):e612. doi: 10.1002/mgg3.612. Epub 2019 Mar 4.
24 Holt-Oram syndrome: a clinical genetic study.J Med Genet. 1996 Apr;33(4):300-7. doi: 10.1136/jmg.33.4.300.
25 Osteosarcoma cell lines display variable individual reactions on wildtype p53 and Rb tumour-suppressor transgenes.J Gene Med. 2005 Apr;7(4):407-19. doi: 10.1002/jgm.684.
26 Down-regulation of miR-10a-5p promotes proliferation and restricts apoptosis via targeting T-box transcription factor 5 in inflamed synoviocytes.Biosci Rep. 2018 Apr 13;38(2):BSR20180003. doi: 10.1042/BSR20180003. Print 2018 Apr 27.
27 Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
28 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
29 Low concentrations of alendronate increase the local invasive potential of osteoblastic sarcoma cell lines via connexin 43 activation.Pathol Res Pract. 2011 Jul 15;207(7):417-22. doi: 10.1016/j.prp.2011.04.007. Epub 2011 Jun 12.
30 Combined MET inhibition and topoisomerase I inhibition block cell growth of small cell lung cancer.Mol Cancer Ther. 2014 Mar;13(3):576-84. doi: 10.1158/1535-7163.MCT-13-0109. Epub 2013 Dec 10.
31 Overexpression of GML promotes radiation-induced cell cycle arrest and apoptosis.Biochem Biophys Res Commun. 1997 Dec 18;241(2):481-5. doi: 10.1006/bbrc.1997.7818.
32 Identification and functional analysis of genetic variants in TBX5 gene promoter in patients with acute myocardial infarction.BMC Cardiovasc Disord. 2019 Nov 27;19(1):265. doi: 10.1186/s12872-019-1237-6.
33 Tip60-dependent acetylation of KDM2B promotes osteosarcoma carcinogenesis.J Cell Mol Med. 2019 Sep;23(9):6154-6163. doi: 10.1111/jcmm.14497. Epub 2019 Jun 20.
34 The diagnostic value of next generation sequencing in familial nonsyndromic congenital heart defects.Am J Med Genet A. 2015 Aug;167A(8):1822-9. doi: 10.1002/ajmg.a.37108. Epub 2015 Apr 30.
35 Fetal Arrhythmias: Genetic Background and Clinical Implications.Pediatr Cardiol. 2019 Feb;40(2):247-256. doi: 10.1007/s00246-018-2008-3. Epub 2018 Nov 26.
36 Optimization of Routine Testing for MET Exon 14 Splice Site Mutations in NSCLC Patients.J Thorac Oncol. 2018 Dec;13(12):1873-1883. doi: 10.1016/j.jtho.2018.08.2023. Epub 2018 Sep 7.
37 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
38 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
39 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
40 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
41 Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.