Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAZ9QDX)

• DOT Name: T-box transcription factor TBX15 (TBX15)
• Synonyms: T-box protein 15; T-box transcription factor TBX14; T-box protein 14
• Gene Name: TBX15
• Related Disease:
  Pelviscapular dysplasia
  Epithelial ovarian cancer
  Neoplasm
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Advanced cancer
  Alopecia
  Androgenetic alopecia
  Baldness, male pattern
• UniProt ID: TBX15_HUMAN
• Pfam ID: PF00907
• Sequence:
  MSERRRSAVALSSRAHAFSVEALIGSNKKRKLRDWEEKGLDLSMEALSPAGPLGDTEDAA
  AHGLEPHPDSEQSTGSDSEVLTERTSCSFSTHTDLASGAAGPVPAAMSSMEEIQVELQCA
  DLWKRFHDIGTEMIITKAGRRMFPAMRVKITGLDPHQQYYIAMDIVPVDNKRYRYVYHSS
  KWMVAGNADSPVPPRVYIHPDSLASGDTWMRQVVSFDKLKLTNNELDDQGHIILHSMHKY
  QPRVHVIRKDFSSDLSPTKPVPVGDGVKTFNFPETVFTTVTAYQNQQITRLKIDRNPFAK
  GFRDSGRNRTGLEAIMETYAFWRPPVRTLTFEDFTTMQKQQGGSTGTSPTTSSTGTPSPS
  ASSHLLSPSCSPPTFHLAPNTFNVGCRESQLCNLNLSDYPPCARSNMAALQSYPGLSDSG
  YNRLQSGTTSATQPSETFMPQRTPSLISGIPTPPSLPGNSKMEAYGGQLGSFPTSQFQYV
  MQAGNAASSSSSPHMFGGSHMQQSSYNAFSLHNPYNLYGYNFPTSPRLAASPEKLSASQS
  TLLCSSPSNGAFGERQYLPSGMEHSMHMISPSPNNQQATNTCDGRQYGAVPGSSSQMSVH
  MV
• Function: Probable transcriptional regulator involved in the development of the skeleton of the limb, vertebral column and head. Acts by controlling the number of mesenchymal precursor cells and chondrocytes.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pelviscapular dysplasia	DISPNJ3R	Definitive	Autosomal recessive	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Obesity	DIS47Y1K	Strong	Biomarker	[4]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[2]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Altered Expression	[5]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[5]
Thyroid cancer	DIS3VLDH	moderate	Biomarker	[6]
Thyroid gland carcinoma	DISMNGZ0	moderate	Biomarker	[6]
Thyroid tumor	DISLVKMD	moderate	Biomarker	[6]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[5]
Alopecia	DIS37HU4	Limited	Genetic Variation	[7]
Androgenetic alopecia	DISSJR1P	Limited	Genetic Variation	[8]
Baldness, male pattern	DIS9C9RO	Limited	Genetic Variation	[8]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of T-box transcription factor TBX15 (TBX15).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of T-box transcription factor TBX15 (TBX15).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of T-box transcription factor TBX15 (TBX15).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of T-box transcription factor TBX15 (TBX15).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of T-box transcription factor TBX15 (TBX15).	[13]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of T-box transcription factor TBX15 (TBX15).	[13]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of T-box transcription factor TBX15 (TBX15).	[14]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of T-box transcription factor TBX15 (TBX15).	[15]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of T-box transcription factor TBX15 (TBX15).	[16]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of T-box transcription factor TBX15 (TBX15).	[19]

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 increases the methylation of T-box transcription factor TBX15 (TBX15).	[17]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the methylation of T-box transcription factor TBX15 (TBX15).	[18]

References

• [1] TBX15 mutations cause craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature in Cousin syndrome. Am J Hum Genet. 2008 Nov;83(5):649-55. doi: 10.1016/j.ajhg.2008.10.011.
• [2] Ovarian cancer detection by DNA methylation in cervical scrapings.Clin Epigenetics. 2019 Nov 27;11(1):166. doi: 10.1186/s13148-019-0773-3.
• [3] Distinct DNA methylation alterations are associated with cribriform architecture and intraductal carcinoma in Gleason pattern 4 prostate tumors.Oncol Lett. 2017 Jul;14(1):390-396. doi: 10.3892/ol.2017.6140. Epub 2017 May 9.
• [4] Tbx15 is required for adipocyte browning induced by adrenergic signaling pathway.Mol Metab. 2019 Oct;28:48-57. doi: 10.1016/j.molmet.2019.07.004. Epub 2019 Jul 5.
• [5] NF-B Mediates the Expression of TBX15 in Cancer Cells.PLoS One. 2016 Jun 21;11(6):e0157761. doi: 10.1371/journal.pone.0157761. eCollection 2016.
• [6] Novel antiapoptotic effect of TBX15: overexpression of TBX15 reduces apoptosis in cancer cells.Apoptosis. 2015 Oct;20(10):1338-46. doi: 10.1007/s10495-015-1155-8.
• [7] Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
• [8] GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk.Nat Commun. 2017 Nov 17;8(1):1584. doi: 10.1038/s41467-017-01490-8.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [11] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [13] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [14] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [17] 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.
• [18] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [19] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.