Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO2IDDR)

• DOT Name: Syntaxin-2 (STX2)
• Synonyms: Epimorphin
• Gene Name: STX2
• Related Disease:
  Anxiety
  Anxiety disorder
  Bacillary dysentery
  Cleft palate
  Colorectal carcinoma
  Depression
  Enterocolitis
  Gastroenteritis
  Giardiasis
  Hepatitis C virus infection
  Inflammatory bowel disease
  Intestinal disorder
  Isolated cleft palate
  Male infertility
  Nephropathy
  Pancreatitis
  Pulmonary fibrosis
  Renal fibrosis
  Ulcerative colitis
  Von Willebrand disease 1
  Bipolar disorder
  Schizoaffective disorder
  Schizophrenia
  Kidney failure
  Advanced cancer
  Escherichia coli infection
  Neoplasm
  Spermatogenic failure
  Thrombocytopenia
• UniProt ID: STX2_HUMAN
• Pfam ID: PF05739 ; PF00804
• Sequence:
  MRDRLPDLTACRKNDDGDTVVVVEKDHFMDDFFHQVEEIRNSIDKITQYVEEVKKNHSII
  LSAPNPEGKIKEELEDLNKEIKKTANKIRAKLKAIEQSFDQDESGNRTSVDLRIRRTQHS
  VLSRKFVEAMAEYNEAQTLFRERSKGRIQRQLEITGRTTTDDELEEMLESGKPSIFTSDI
  ISDSQITRQALNEIESRHKDIMKLETSIRELHEMFMDMAMFVETQGEMINNIERNVMNAT
  DYVEHAKEETKKAIKYQSKARRKKWIIIAVSVVLVAIIALIIGLSVGK
• Function: Essential for epithelial morphogenesis. May mediate Ca(2+)-regulation of exocytosis acrosomal reaction in sperm.
• KEGG Pathway:
  S.RE interactions in vesicular transport (hsa04130)
  Sy.ptic vesicle cycle (hsa04721)

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Strong	Biomarker	[1]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[1]
Bacillary dysentery	DISFZHKN	Strong	Biomarker	[2]
Cleft palate	DIS6G5TF	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Depression	DIS3XJ69	Strong	Biomarker	[5]
Enterocolitis	DISYACTL	Strong	Biomarker	[6]
Gastroenteritis	DISXQCG5	Strong	Biomarker	[7]
Giardiasis	DISWUNWK	Strong	Biomarker	[8]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[9]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[10]
Intestinal disorder	DISGPMUQ	Strong	Genetic Variation	[11]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[3]
Male infertility	DISY3YZZ	Strong	Biomarker	[12]
Nephropathy	DISXWP4P	Strong	Biomarker	[13]
Pancreatitis	DIS0IJEF	Strong	Biomarker	[14]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[15]
Renal fibrosis	DISMHI3I	Strong	Altered Expression	[16]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[10]
Von Willebrand disease 1	DISUGLZA	Strong	Genetic Variation	[17]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[18]
Schizoaffective disorder	DISLBW6B	moderate	Genetic Variation	[18]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[18]
Kidney failure	DISOVQ9P	Disputed	Biomarker	[13]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[19]
Escherichia coli infection	DISPP65M	Limited	Biomarker	[20]
Neoplasm	DISZKGEW	Limited	Altered Expression	[21]
Spermatogenic failure	DIS3D1AI	Limited	Autosomal recessive	[22]
Thrombocytopenia	DISU61YW	Limited	Biomarker	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Syntaxin-2 (STX2).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Syntaxin-2 (STX2).	[25]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Syntaxin-2 (STX2).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Syntaxin-2 (STX2).	[27]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Syntaxin-2 (STX2).	[28]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Syntaxin-2 (STX2).	[29]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Syntaxin-2 (STX2).	[30]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Syntaxin-2 (STX2).	[31]

1 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 Syntaxin-2 (STX2).	[32]

References

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• [2] Rapid SNP Detection and Genotyping of Bacterial Pathogens by Pyrosequencing.Methods Mol Biol. 2017;1492:203-220. doi: 10.1007/978-1-4939-6442-0_15.
• [3] Inhibition of periderm removal in all-trans retinoic acid-induced cleft palate in mice.Exp Ther Med. 2017 Oct;14(4):3393-3398. doi: 10.3892/etm.2017.4938. Epub 2017 Aug 16.
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• [7] Strong association between shiga toxin-producing Escherichia coli O157 and virulence genes stx2 and eae as possible explanation for predominance of serogroup O157 in patients with haemolytic uraemic syndrome.Eur J Clin Microbiol Infect Dis. 2003 Dec;22(12):726-30. doi: 10.1007/s10096-003-1025-0. Epub 2003 Nov 12.
• [8] Multicenter evaluation of the new QIAstat Gastrointestinal Panel for the rapid syndromic testing of acute gastroenteritis.Eur J Clin Microbiol Infect Dis. 2019 Nov;38(11):2103-2112. doi: 10.1007/s10096-019-03646-4. Epub 2019 Jul 27.
• [9] HIV and HCV Co-Culture Promotes Profibrogenic Gene Expression through an Epimorphin-Mediated ERK Signaling Pathway in Hepatic Stellate Cells.PLoS One. 2016 Jun 30;11(6):e0158386. doi: 10.1371/journal.pone.0158386. eCollection 2016.
• [10] Altered expression of epimorphin in ulcerative colitis.J Gastroenterol Hepatol. 2003 May;18(5):570-7. doi: 10.1046/j.1440-1746.2003.02972.x.
• [11] Shiga toxin 2 translocation across intestinal epithelium is linked to virulence of Shiga toxin-producing Escherichia coli in humans.Microbiology (Reading). 2018 Apr;164(4):509-516. doi: 10.1099/mic.0.000645. Epub 2018 Mar 13.
• [12] A new ENU-induced mutant mouse with defective spermatogenesis caused by a nonsense mutation of the syntaxin 2/epimorphin (Stx2/Epim) gene.J Reprod Dev. 2008 Apr;54(2):122-8. doi: 10.1262/jrd.19186. Epub 2008 Feb 14.
• [13] Direct acute tubular damage contributes to Shigatoxin-mediated kidney failure.J Pathol. 2014 Sep;234(1):120-33. doi: 10.1002/path.4388. Epub 2014 Jul 25.
• [14] Pancreatitis-Induced Depletion of Syntaxin 2 Promotes Autophagy and Increases Basolateral Exocytosis.Gastroenterology. 2018 May;154(6):1805-1821.e5. doi: 10.1053/j.gastro.2018.01.025. Epub 2018 Jan 31.
• [15] Epimorphin expression in interstitial pneumonia.Respir Res. 2005 Jan 16;6(1):6. doi: 10.1186/1465-9921-6-6.
• [16] Involvement of epimorphin in the repair of experimental renal fibrosis in mice.Lab Invest. 2010 Jun;90(6):867-80. doi: 10.1038/labinvest.2010.50. Epub 2010 Mar 1.
• [17] Effect of genetic variation in STXBP5 and STX2 on von Willebrand factor and bleeding phenotype in type 1 von Willebrand disease patients.PLoS One. 2012;7(7):e40624. doi: 10.1371/journal.pone.0040624. Epub 2012 Jul 6.
• [18] Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.Transl Psychiatry. 2017 Oct 24;7(10):e1249. doi: 10.1038/tp.2017.210.
• [19] Analysis of CYP1A1 and COMT polymorphisms in women with cervical cancer.Genet Mol Res. 2015 Dec 29;14(4):18965-73. doi: 10.4238/2015.December.29.3.
• [20] Cytotoxic effects of Shiga toxin-2 on human extravillous trophoblast cell lines.Reproduction. 2019 Mar;157(3):297-304. doi: 10.1530/REP-18-0581.
• [21] The efficacy of recombinant human soluble thrombomodulin for the treatment of shiga toxin-associated hemolytic uremic syndrome model mice.Nephrol Dial Transplant. 2015 Jun;30(6):969-77. doi: 10.1093/ndt/gfv004. Epub 2015 Feb 17.
• [22] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [23] Alternative pathway activation of complement by Shiga toxin promotes exuberant C3a formation that triggers microvascular thrombosis.J Immunol. 2011 Jul 1;187(1):172-80. doi: 10.4049/jimmunol.1100491. Epub 2011 Jun 3.
• [24] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [25] 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.
• [26] 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.
• [27] 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.
• [28] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [29] 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.
• [30] 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.
• [31] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [32] 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.