Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIF1O1T)

• DOT Name: Testis-specific gene 10 protein (TSGA10)
• Synonyms: Testis development protein NYD-SP7
• Gene Name: TSGA10
• Related Disease:
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Advanced cancer
  Autoimmune disease
  Autoimmune polyendocrine syndrome type 1
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Childhood acute lymphoblastic leukemia
  Colon cancer
  Colonic neoplasm
  Esophageal squamous cell carcinoma
  Haematological malignancy
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Melanoma
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate neoplasm
  Skin neoplasm
  Soft tissue neoplasm
  Systemic lupus erythematosus
  Testicular cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Bladder cancer
  Neoplasm
  Nasopharyngeal carcinoma
  Spermatogenic failure 26
• UniProt ID: TSG10_HUMAN
• Sequence:
  MMRSRSKSPRRPSPTARGANCDVELLKTTTRDREELKCMLEKYERHLAEIQGNVKVLKSE
  RDKIFLLYEQAQEEITRLRREMMKSCKSPKSTTAHAILRRVETERDVAFTDLRRMTTERD
  SLRERLKIAQETAFNEKAHLEQRIEELECTVHNLDDERMEQMSNMTLMKETISTVEKEMK
  SLARKAMDTESELGRQKAENNSLRLLYENTEKDLSDTQRHLAKKKYELQLTQEKIMCLDE
  KIDNFTRQNIAQREEISILGGTLNDLAKEKECLQACLDKKSENIASLGESLAMKEKTISG
  MKNIIAEMEQASRQCTEALIVCEQDVSRMRRQLDETNDELAQIARERDILAHDNDNLQEQ
  FAKAKQENQALSKKLNDTHNELNDIKQKVQDTNLEVNKLKNILKSEESENRQMMEQLRKA
  NEDAENWENKARQSEADNNTLKLELITAEAEGNRLKEKVDSLNREVEQHLNAERSYKSQI
  STLHKSVVKMEEELQKVQFEKVSALADLSSTRELCIKLDSSKELLNRQLVAKDQEIEMRE
  NELDSAHSEIELLRSQMANERISMQNLEALLVANRDKEYQSQIALQEKESEIQLLKEHLC
  LAENKMAIQSRDVAQFRNVVTQLEADLDITKRQLGTERFERERAVQELRRQNYSSNAYHM
  SSTMKPNTKCHSPERAHHRSPDRGLDRSLEENLCYRDF
• Function: Plays a role in spermatogenesis. When overexpressed, prevents nuclear localization of HIF1A.
• Tissue Specificity: Expressed in the testis, in spermatozoa (at protein level) . Expressed in actively dividing fetal tissues, including sternum, intestine, limb, kidney and stomach .

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
Autoimmune polyendocrine syndrome type 1	DISWJP8J	Strong	Biomarker	[4]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[6]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[6]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[7]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[8]
Haematological malignancy	DISCDP7W	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
leukaemia	DISS7D1V	Strong	Altered Expression	[1]
Leukemia	DISNAKFL	Strong	Altered Expression	[1]
Melanoma	DIS1RRCY	Strong	Altered Expression	[7]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[7]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[7]
Prostate cancer	DISF190Y	Strong	Altered Expression	[7]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[7]
Skin neoplasm	DIS16DDV	Strong	Altered Expression	[5]
Soft tissue neoplasm	DISP2OHE	Strong	Altered Expression	[5]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[4]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[6]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	moderate	Biomarker	[3]
Neoplasm	DISZKGEW	moderate	Altered Expression	[9]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[10]
Spermatogenic failure 26	DISG7TDJ	Limited	Unknown	[11]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Testis-specific gene 10 protein (TSGA10).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Testis-specific gene 10 protein (TSGA10).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Testis-specific gene 10 protein (TSGA10).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Testis-specific gene 10 protein (TSGA10).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Testis-specific gene 10 protein (TSGA10).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Testis-specific gene 10 protein (TSGA10).	[16]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Testis-specific gene 10 protein (TSGA10).	[17]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Testis-specific gene 10 protein (TSGA10).	[18]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Testis-specific gene 10 protein (TSGA10).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Testis-specific gene 10 protein (TSGA10).	[18]
Manganese	DMKT129	Investigative	Manganese increases the expression of Testis-specific gene 10 protein (TSGA10).	[21]

References

• [1] Expression of the testis-specific gene, TSGA10, in Iranian patients with acute lymphoblastic leukemia (ALL).Leuk Res. 2006 Jul;30(7):883-9. doi: 10.1016/j.leukres.2005.11.012. Epub 2006 Jan 6.
• [2] Contribution and prognostic value of TSGA10 gene expression in patients with acute myeloid leukemia (AML).Pathol Res Pract. 2019 Mar;215(3):506-511. doi: 10.1016/j.prp.2019.01.003. Epub 2019 Jan 7.
• [3] Expression of Testis-Specific Gene Antigen 10 (TSGA10) is Associated with Apoptosis and Cell Migration in Bladder Cancer Cells and Tumor Stage and Overall Survival in Patients with Bladder Cancer.Med Sci Monit. 2019 Jul 16;25:5289-5298. doi: 10.12659/MSM.915682.
• [4] TSGA10 - A target for autoantibodies in autoimmune polyendocrine syndrome type 1 and systemic lupus erythematosus.Scand J Immunol. 2011 Feb;73(2):147-53. doi: 10.1111/j.1365-3083.2010.02486.x.
• [5] Expression of two testis-specific genes, TSGA10 and SYCP3, in different cancers regarding to their pathological features.Cancer Detect Prev. 2007;31(4):296-302. doi: 10.1016/j.cdp.2007.05.002.
• [6] Identification of new TSGA10 transcript variants in human testis with conserved regulatory RNA elements in 5'untranslated region and distinct expression in breast cancer.Biochim Biophys Acta Gene Regul Mech. 2017 Sep;1860(9):973-982. doi: 10.1016/j.bbagrm.2017.07.007. Epub 2017 Jul 21.
• [7] Over-expression of the testis-specific gene TSGA10 in cancers and its immunogenicity.Microbiol Immunol. 2004;48(4):339-45. doi: 10.1111/j.1348-0421.2004.tb03515.x.
• [8] Effects and interactions of MiR-577 and TSGA10 in regulating esophageal squamous cell carcinoma.Int J Clin Exp Pathol. 2013 Nov 15;6(12):2651-67. eCollection 2013.
• [9] TSGA10 overexpression inhibits angiogenesis of HUVECs: A HIF-2 biased perspective.Microvasc Res. 2020 Mar;128:103952. doi: 10.1016/j.mvr.2019.103952. Epub 2019 Nov 5.
• [10] Metastasis-associated miR-23a from nasopharyngeal carcinoma-derived exosomes mediates angiogenesis by repressing a novel target gene TSGA10.Oncogene. 2018 May;37(21):2873-2889. doi: 10.1038/s41388-018-0183-6. Epub 2018 Mar 9.
• [11] Is our island sinking? Quality levels in operative dentistry as observed on state board examinations. Oper Dent. 1977 Summer;2(3):111-5.
• [12] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [13] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [14] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [15] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] Identification of biomarkers for the initiation of apoptosis in human preneoplastic colonocytes by proteome analysis. Int J Cancer. 2004 Mar 20;109(2):220-9. doi: 10.1002/ijc.11692.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [20] 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.
• [21] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.