Details of Drug Off-Target (DOT)

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

• DOT Name: Testis-specific Y-encoded-like protein 1 (TSPYL1)
• Synonyms: TSPY-like protein 1
• Gene Name: TSPYL1
• Related Disease:
  Azoospermia
  Depression
  Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome
  Major depressive disorder
  Male infertility
  Sudden infant death-dysgenesis of the testes syndrome
• UniProt ID: TSYL1_HUMAN
• Pfam ID: PF00956
• Sequence:
  MSGLDGVKRTTPLQTHSIIISDQVPSDQDAHQYLRLRDQSEATQVMAEPGEGGSETVALP
  PPPPSEEGGVPQDAAGRGGTPQIRVVGGRGHVAIKAGQEEGQPPAEGLAAASVVMAADRS
  LKKGVQGGEKALEICGAQRSASELTAGAEAEAEEVKTGKCATVSAAVAERESAEVVKEGL
  AEKEVMEEQMEVEEQPPEGEEIEVAEEDRLEEEAREEEGPWPLHEALRMDPLEAIQLELD
  TVNAQADRAFQQLEHKFGRMRRHYLERRNYIIQNIPGFWMTAFRNHPQLSAMIRGQDAEM
  LRYITNLEVKELRHPRTGCKFKFFFRRNPYFRNKLIVKEYEVRSSGRVVSLSTPIIWRRG
  HEPQSFIRRNQDLICSFFTWFSDHSLPESDKIAEIIKEDLWPNPLQYYLLREGVRRARRR
  PLREPVEIPRPFGFQSG
• Tissue Specificity: Expressed in testis, ovary, liver, spleen, brain, kidney, prostate, lung, liver, and heart.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Azoospermia	DIS94181	Strong	Genetic Variation	[1]
Depression	DIS3XJ69	Strong	Genetic Variation	[2]
Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome	DISD21FA	Strong	Altered Expression	[3]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[1]
Sudden infant death-dysgenesis of the testes syndrome	DIS7C4ZZ	Strong	Autosomal recessive	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Testis-specific Y-encoded-like protein 1 (TSPYL1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Testis-specific Y-encoded-like protein 1 (TSPYL1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Testis-specific Y-encoded-like protein 1 (TSPYL1).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Testis-specific Y-encoded-like protein 1 (TSPYL1).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Testis-specific Y-encoded-like protein 1 (TSPYL1).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Testis-specific Y-encoded-like protein 1 (TSPYL1).	[12]

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 Testis-specific Y-encoded-like protein 1 (TSPYL1).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Testis-specific Y-encoded-like protein 1 (TSPYL1).	[9]

References

• [1] Should TSPYL1 mutation screening be included in routine diagnostics of male idiopathic infertility?.Fertil Steril. 2012 Feb;97(2):402-6. doi: 10.1016/j.fertnstert.2011.11.002. Epub 2011 Dec 2.
• [2] Dual Roles for the TSPYL Family in Mediating Serotonin Transport and the Metabolism of Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder.Clin Pharmacol Ther. 2020 Mar;107(3):662-670. doi: 10.1002/cpt.1692. Epub 2019 Nov 30.
• [3] Identification of novel candidate genes for globin regulation in erythroid cells containing large deletions of the human beta-globin gene cluster.Blood Cells Mol Dis. 2006 Sep-Oct;37(2):82-90. doi: 10.1016/j.bcmd.2006.07.003. Epub 2006 Sep 6.
• [4] Mapping of sudden infant death with dysgenesis of the testes syndrome (SIDDT) by a SNP genome scan and identification of TSPYL loss of function. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11689-94. doi: 10.1073/pnas.0401194101. Epub 2004 Jul 23.
• [5] 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.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.