Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUIQ81Q)

• DOT Name: Synaptosomal-associated protein 25 (SNAP25)
• Synonyms: SNAP-25; Super protein; SUP; Synaptosomal-associated 25 kDa protein
• Gene Name: SNAP25
• Related Disease:
  Infantile spasm
  Congenital myasthenic syndrome 18
  Obsolete presynaptic congenital myasthenic syndrome
• UniProt ID: SNP25_HUMAN
• PDB ID: 1KIL; 1XTG; 2N1T; 3DDA; 3DDB; 3RK2; 3RK3; 3RL0; 3ZUR; 5W7I; 5W7J; 6JLH
• Pfam ID: PF00835
• Sequence:
  MAEDADMRNELEEMQRRADQLADESLESTRRMLQLVEESKDAGIRTLVMLDEQGEQLERI
  EEGMDQINKDMKEAEKNLTDLGKFCGLCVCPCNKLKSSDAYKKAWGNNQDGVVASQPARV
  VDEREQMAISGGFIRRVTNDARENEMDENLEQVSGIIGNLRHMALDMGNEIDTQNRQIDR
  IMEKADSNKTRIDEANQRATKMLGSG
• Function: t-SNARE involved in the molecular regulation of neurotransmitter release. May play an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesicle docking and membrane fusion. Regulates plasma membrane recycling through its interaction with CENPF. Modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 in pancreatic beta cells.
• Tissue Specificity: Neurons of the neocortex, hippocampus, piriform cortex, anterior thalamic nuclei, pontine nuclei, and granule cells of the cerebellum.
• KEGG Pathway:
  Sy.ptic vesicle cycle (hsa04721)
  Insulin secretion (hsa04911)
• Reactome Pathway:
  Norepinephrine Neurotransmitter Release Cycle (R-HSA-181430)
  Glutamate Neurotransmitter Release Cycle (R-HSA-210500)
  Dopamine Neurotransmitter Release Cycle (R-HSA-212676)
  Acetylcholine Neurotransmitter Release Cycle (R-HSA-264642)
  Regulation of insulin secretion (R-HSA-422356)
  Other interleukin signaling (R-HSA-449836)
  Toxicity of botulinum toxin type A (botA) (R-HSA-5250968)
  Toxicity of botulinum toxin type C (botC) (R-HSA-5250971)
  Toxicity of botulinum toxin type E (botE) (R-HSA-5250992)
  Neutrophil degranulation (R-HSA-6798695)
  GABA synthesis, release, reuptake and degradation (R-HSA-888590)
  Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)
  Serotonin Neurotransmitter Release Cycle (R-HSA-181429)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Infantile spasm	DISZSKDG	Definitive	Autosomal dominant	[1]
Congenital myasthenic syndrome 18	DIS1GVCK	Strong	Autosomal dominant	[2]
Obsolete presynaptic congenital myasthenic syndrome	DISCATK3	Supportive	Autosomal dominant	[2]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Clozapine	DMFC71L	Approved	Synaptosomal-associated protein 25 (SNAP25) affects the response to substance of Clozapine.	[22]
Haloperidol	DM96SE0	Approved	Synaptosomal-associated protein 25 (SNAP25) affects the response to substance of Haloperidol.	[22]
Olanzapine	DMPFN6Y	Approved	Synaptosomal-associated protein 25 (SNAP25) affects the response to substance of Olanzapine.	[22]
Risperidone	DMN6DXL	Approved	Synaptosomal-associated protein 25 (SNAP25) affects the response to substance of Risperidone.	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Synaptosomal-associated protein 25 (SNAP25).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Synaptosomal-associated protein 25 (SNAP25).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Synaptosomal-associated protein 25 (SNAP25).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Synaptosomal-associated protein 25 (SNAP25).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Synaptosomal-associated protein 25 (SNAP25).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Synaptosomal-associated protein 25 (SNAP25).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Synaptosomal-associated protein 25 (SNAP25).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Synaptosomal-associated protein 25 (SNAP25).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Synaptosomal-associated protein 25 (SNAP25).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Synaptosomal-associated protein 25 (SNAP25).	[12]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Synaptosomal-associated protein 25 (SNAP25).	[10]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Synaptosomal-associated protein 25 (SNAP25).	[13]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine decreases the expression of Synaptosomal-associated protein 25 (SNAP25).	[14]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Synaptosomal-associated protein 25 (SNAP25).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Synaptosomal-associated protein 25 (SNAP25).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Synaptosomal-associated protein 25 (SNAP25).	[18]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Synaptosomal-associated protein 25 (SNAP25).	[19]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Synaptosomal-associated protein 25 (SNAP25).	[20]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Synaptosomal-associated protein 25 (SNAP25).	[21]

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 increases the methylation of Synaptosomal-associated protein 25 (SNAP25).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Synaptosomal-associated protein 25 (SNAP25).	[17]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and intellectual disability. Neurology. 2014 Dec 9;83(24):2247-55. doi: 10.1212/WNL.0000000000001079. Epub 2014 Nov 7.
• [3] Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Toxicol Sci. 2023 Sep 28;195(2):169-183. doi: 10.1093/toxsci/kfad076.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [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] Casodex treatment induces hypoxia-related gene expression in the LNCaP prostate cancer progression model. BMC Urol. 2005 Mar 24;5:5.
• [14] Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse. Neuropsychopharmacology. 2006 Oct;31(10):2304-12. doi: 10.1038/sj.npp.1301089. Epub 2006 May 3.
• [15] 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.
• [16] 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.
• [17] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [18] 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.
• [19] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [20] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [21] Vesicle transport related protein Synaptotagmin-1 mediates paraquat transport to antagonize paraquat toxicity. Toxicology. 2022 Apr 30;472:153180. doi: 10.1016/j.tox.2022.153180. Epub 2022 Apr 18.
• [22] The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia. Neurosci Lett. 2005 May 6;379(2):81-9. doi: 10.1016/j.neulet.2004.12.037. Epub 2005 Jan 26.