Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWKX0AZ)

• DOT Name: Spermatogenesis-associated protein 20 (SPATA20)
• Synonyms: Sperm-specific protein 411; Ssp411
• Gene Name: SPATA20
• Related Disease:
  Cholangiocarcinoma
  Male infertility
• UniProt ID: SPT20_HUMAN
• Pfam ID: PF03190
• Sequence:
  MLGARAWLGRVLLLPRAGAGLAASRRGSSSRDKDRSATVSSSVPMPAGGKGSHPSSTPQR
  VPNRLIHEKSPYLLQHAYNPVDWYPWGQEAFDKARKENKPIFLSVGYSTCHWCHMMEEES
  FQNEEIGRLLSEDFVSVKVDREERPDVDKVYMTFVQATSSGGGWPMNVWLTPNLQPFVGG
  TYFPPEDGLTRVGFRTVLLRIREQWKQNKNTLLENSQRVTTALLARSEISVGDRQLPPSA
  ATVNNRCFQQLDEGYDEEYGGFAEAPKFPTPVILSFLFSYWLSHRLTQDGSRAQQMALHT
  LKMMANGGIRDHVGQGFHRYSTDRQWHVPHFEKMLYDQAQLAVAYSQAFQLSGDEFYSDV
  AKGILQYVARSLSHRSGGFYSAEDADSPPERGQRPKEGAYYVWTVKEVQQLLPEPVLGAT
  EPLTSGQLLMKHYGLTEAGNISPSQDPKGELQGQNVLTVRYSLELTAARFGLDVEAVRTL
  LNSGLEKLFQARKHRPKPHLDSKMLAAWNGLMVSGYAVTGAVLGQDRLINYATNGAKFLK
  RHMFDVASGRLMRTCYTGPGGTVEHSNPPCWGFLEDYAFVVRGLLDLYEASQESAWLEWA
  LRLQDTQDKLFWDSQGGGYFCSEAELGAGLPLRLKDDQDGAEPSANSVSAHNLLRLHGFT
  GHKDWMDKCVCLLTAFSERMRRVPVALPEMVRALSAQQQTLKQIVICGDRQAKDTKALVQ
  CVHSVYIPNKVLILADGDPSSFLSRQLPFLSTLRRLEDQATAYVCENQACSVPITDPCEL
  RKLLHP
• Function: May play a role in fertility regulation.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[1]
Male infertility	DISY3YZZ	Strong	Biomarker	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Spermatogenesis-associated protein 20 (SPATA20) decreases the response to substance of Arsenic trioxide.	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Spermatogenesis-associated protein 20 (SPATA20).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Spermatogenesis-associated protein 20 (SPATA20).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Spermatogenesis-associated protein 20 (SPATA20).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Spermatogenesis-associated protein 20 (SPATA20).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Spermatogenesis-associated protein 20 (SPATA20).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Spermatogenesis-associated protein 20 (SPATA20).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Spermatogenesis-associated protein 20 (SPATA20).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Spermatogenesis-associated protein 20 (SPATA20).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Spermatogenesis-associated protein 20 (SPATA20).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Spermatogenesis-associated protein 20 (SPATA20).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Spermatogenesis-associated protein 20 (SPATA20).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Spermatogenesis-associated protein 20 (SPATA20).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Spermatogenesis-associated protein 20 (SPATA20).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Spermatogenesis-associated protein 20 (SPATA20).	[14]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Spermatogenesis-associated protein 20 (SPATA20).	[16]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Spermatogenesis-associated protein 20 (SPATA20).	[17]

References

• [1] Comparative proteomic profiling of human bile reveals SSP411 as a novel biomarker of cholangiocarcinoma.PLoS One. 2012;7(10):e47476. doi: 10.1371/journal.pone.0047476. Epub 2012 Oct 31.
• [2] Disruption of Ssp411 causes impaired sperm head formation and male sterility in mice.Biochim Biophys Acta Gen Subj. 2018 Mar;1862(3):660-668. doi: 10.1016/j.bbagen.2017.12.005. Epub 2017 Dec 13.
• [3] 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.
• [4] 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.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [14] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [15] Genome-wide alteration in DNA hydroxymethylation in the sperm from bisphenol A-exposed men. PLoS One. 2017 Jun 5;12(6):e0178535. doi: 10.1371/journal.pone.0178535. eCollection 2017.
• [16] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [17] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.
• [18] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.