Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHW3GEI)

• DOT Name: Syntaxin-7 (STX7)
• Gene Name: STX7
• Related Disease:
  Hepatitis C virus infection
  Microcephaly
  Schizophrenia
  Neoplasm
• UniProt ID: STX7_HUMAN
• Pfam ID: PF05739 ; PF14523
• Sequence:
  MSYTPGVGGDPAQLAQRISSNIQKITQCSVEIQRTLNQLGTPQDSPELRQQLQQKQQYTN
  QLAKETDKYIKEFGSLPTTPSEQRQRKIQKDRLVAEFTTSLTNFQKVQRQAAEREKEFVA
  RVRASSRVSGSFPEDSSKERNLVSWESQTQPQVQVQDEEITEDDLRLIHERESSIRQLEA
  DIMDINEIFKDLGMMIHEQGDVIDSIEANVENAEVHVQQANQQLSRAADYQRKSRKTLCI
  IILILVIGVAIISLIIWGLNH
• Function: May be involved in protein trafficking from the plasma membrane to the early endosome (EE) as well as in homotypic fusion of endocytic organelles. Mediates the endocytic trafficking from early endosomes to late endosomes and lysosomes.
• Tissue Specificity: Highest expression is found in placenta followed by heart, skeletal muscle, kidney and brain. Low expression is found in pancreas, lung and liver.
• KEGG Pathway:
  S.RE interactions in vesicular transport (hsa04130)
  Autophagy - animal (hsa04140)
  Phagosome (hsa04145)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[1]
Microcephaly	DIS2GRD8	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]
Neoplasm	DISZKGEW	Limited	Biomarker	[4]

3 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 Syntaxin-7 (STX7).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Syntaxin-7 (STX7).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Syntaxin-7 (STX7).	[13]

10 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 Syntaxin-7 (STX7).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Syntaxin-7 (STX7).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Syntaxin-7 (STX7).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Syntaxin-7 (STX7).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Syntaxin-7 (STX7).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Syntaxin-7 (STX7).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Syntaxin-7 (STX7).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Syntaxin-7 (STX7).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Syntaxin-7 (STX7).	[16]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Syntaxin-7 (STX7).	[17]

References

• [1] HCV-induced autophagosomes are generated via homotypic fusion of phagophores that mediate HCV RNA replication.PLoS Pathog. 2017 Sep 19;13(9):e1006609. doi: 10.1371/journal.ppat.1006609. eCollection 2017 Sep.
• [2] Mosaic parental germline mutations causing recurrent forms of malformations of cortical development.Eur J Hum Genet. 2016 Apr;24(4):611-4. doi: 10.1038/ejhg.2015.192. Epub 2015 Sep 23.
• [3] Polymorphisms in the trace amine receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia.Am J Hum Genet. 2004 Oct;75(4):624-38. doi: 10.1086/424887. Epub 2004 Aug 24.
• [4] Affinity Proteomics Exploration of Melanoma Identifies Proteins in Serum with Associations to T-Stage and Recurrence.Transl Oncol. 2017 Jun;10(3):385-395. doi: 10.1016/j.tranon.2017.03.002. Epub 2017 Apr 20.
• [5] 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.
• [6] 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.
• [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] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.
• [12] 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.
• [13] 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.
• [14] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [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.
• [17] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.