Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5IBQ62)

• DOT Name: Syntaxin-12 (STX12)
• Gene Name: STX12
• Related Disease:
  Cholelithiasis
  Chronic pancreatitis
• UniProt ID: STX12_HUMAN
• PDB ID: 2DNX
• Pfam ID: PF05739 ; PF14523
• Sequence:
  MSYGPLDMYRNPGPSGPQLRDFSSIIQTCSGNIQRISQATAQIKNLMSQLGTKQDSSKLQ
  ENLQQLQHSTNQLAKETNELLKELGSLPLPLSTSEQRQQRLQKERLMNDFSAALNNFQAV
  QRRVSEKEKESIARARAGSRLSAEERQREEQLVSFDSHEEWNQMQSQEDEVAITEQDLEL
  IKERETAIRQLEADILDVNQIFKDLAMMIHDQGDLIDSIEANVESSEVHVERATEQLQRA
  AYYQKKSRKKMCILVLVLSVIILILGLIIWLVYKTK
• Function: SNARE promoting fusion of transport vesicles with target membranes. Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane, and may therefore function in the endocytic recycling pathway. Through complex formation with GRIP1, GRIA2 and NSG1 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting.
• KEGG Pathway: Phagosome (hsa04145)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholelithiasis	DISERLZB	Strong	Genetic Variation	[1]
Chronic pancreatitis	DISBUOMJ	Limited	Biomarker	[2]

12 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 Syntaxin-12 (STX12).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Syntaxin-12 (STX12).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Syntaxin-12 (STX12).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Syntaxin-12 (STX12).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Syntaxin-12 (STX12).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Syntaxin-12 (STX12).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Syntaxin-12 (STX12).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Syntaxin-12 (STX12).	[11]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Syntaxin-12 (STX12).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Syntaxin-12 (STX12).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Syntaxin-12 (STX12).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Syntaxin-12 (STX12).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Syntaxin-12 (STX12).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Syntaxin-12 (STX12).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Syntaxin-12 (STX12).	[14]

References

• [1] A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease.Nat Genet. 2007 Aug;39(8):995-9. doi: 10.1038/ng2101. Epub 2007 Jul 15.
• [2] STX12 lncRNA/miR-148a/SMAD5 participate in the regulation of pancreatic stellate cell activation through a mechanism involving competing endogenous RNA.Pancreatology. 2017 Mar-Apr;17(2):237-246. doi: 10.1016/j.pan.2017.01.010. Epub 2017 Feb 1.
• [3] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] 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.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res. 2012 Apr 1;18(7):1979-91. doi: 10.1158/1078-0432.CCR-11-2113. Epub 2012 Feb 20.
• [13] 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.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [15] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.