Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK0DEGH)

• DOT Name: Synapsin-2 (SYN2)
• Synonyms: Synapsin II
• Gene Name: SYN2
• Related Disease:
  Alzheimer disease
  Atrial septal defect
  Autism
  Autism spectrum disorder
  B-cell lymphoma
  Epilepsy, idiopathic generalized
  Hairy cell leukaemia
  Major depressive disorder
  Mood disorder
  Neoplasm
  Osteoporosis
  Type-1/2 diabetes
  Urticaria
  Alcohol dependence
  Nervous system inflammation
• UniProt ID: SYN2_HUMAN
• Pfam ID: PF02078 ; PF02750 ; PF10581
• Sequence:
  MMNFLRRRLSDSSFIANLPNGYMTDLQRPEPQQPPPPPPPGPGAASASAAPPTASPGPER
  RPPPASAPAPQPAPTPSVGSSFFSSLSQAVKQTAASAGLVDAPAPAPAAARKAKVLLVVD
  EPHADWAKCFRGKKVLGDYDIKVEQAEFSELNLVAHADGTYAVDMQVLRNGTKVVRSFRP
  DFVLIRQHAFGMAENEDFRHLIIGMQYAGLPSINSLESIYNFCDKPWVFAQLVAIYKTLG
  GEKFPLIEQTYYPNHKEMLTLPTFPVVVKIGHAHSGMGKVKVENHYDFQDIASVVALTQT
  YATAEPFIDSKYDIRVQKIGNNYKAYMRTSISGNWKTNTGSAMLEQIAMSDRYKLWVDTC
  SEMFGGLDICAVKAVHGKDGKDYIFEVMDCSMPLIGEHQVEDRQLITELVISKMNQLLSR
  TPALSPQRPLTTQQPQSGTLKDPDSSKTPPQRPPPQGGPGQPQGMQPPGKVLPPRRLPPG
  PSLPPSSSSSSSSSSSAPQRPGGPTTHGDAPSSSSSLAEAQPPLAAPPQKPQPHPQLNKS
  QSLTNAFSFSESSFFRSSANEDEAKAETIRSLRKSFASLFSD
• Function: Neuronal phosphoprotein that coats synaptic vesicles, binds to the cytoskeleton, and is believed to function in the regulation of neurotransmitter release. May play a role in noradrenaline secretion by sympathetic neurons.
• Tissue Specificity: Central and peripheral nervous systems.
• Reactome Pathway:
  Dopamine Neurotransmitter Release Cycle (R-HSA-212676)
  Serotonin Neurotransmitter Release Cycle (R-HSA-181429)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Altered Expression	[1]
Atrial septal defect	DISJT76B	Strong	Biomarker	[2]
Autism	DISV4V1Z	Strong	Biomarker	[3]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[4]
Epilepsy, idiopathic generalized	DISODZC9	Strong	Genetic Variation	[5]
Hairy cell leukaemia	DISTD2E5	Strong	Biomarker	[6]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[7]
Mood disorder	DISLVMWO	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Osteoporosis	DISF2JE0	Strong	Biomarker	[9]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[10]
Urticaria	DIS9WQAI	Strong	Biomarker	[11]
Alcohol dependence	DIS4ZSCO	moderate	Genetic Variation	[12]
Nervous system inflammation	DISB3X5A	Limited	Altered Expression	[13]

8 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 Synapsin-2 (SYN2).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Synapsin-2 (SYN2).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Synapsin-2 (SYN2).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Synapsin-2 (SYN2).	[17]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Synapsin-2 (SYN2).	[18]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Synapsin-2 (SYN2).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Synapsin-2 (SYN2).	[21]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Synapsin-2 (SYN2).	[23]

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 Synapsin-2 (SYN2).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Synapsin-2 (SYN2).	[22]

References

• [1] Human Alzheimer's disease synaptic O-GlcNAc site mapping and iTRAQ expression proteomics with ion trap mass spectrometry.Amino Acids. 2011 Mar;40(3):765-79. doi: 10.1007/s00726-010-0645-9. Epub 2010 Jun 19.
• [2] The Knockout of Synapsin II in Mice Impairs Social Behavior and Functional Connectivity Generating an ASD-like Phenotype.Cereb Cortex. 2017 Oct 1;27(10):5014-5023. doi: 10.1093/cercor/bhx207.
• [3] SYN2 is an autism predisposing gene: loss-of-function mutations alter synaptic vesicle cycling and axon outgrowth.Hum Mol Genet. 2014 Jan 1;23(1):90-103. doi: 10.1093/hmg/ddt401. Epub 2013 Aug 15.
• [4] Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B-cell lymphoma cells and their association with clinical features.Cancer Med. 2016 Aug;5(8):1802-9. doi: 10.1002/cam4.753. Epub 2016 May 17.
• [5] Association of GABRA6 1519 T>C (rs3219151) and Synapsin II (rs37733634) gene polymorphisms with the development of idiopathic generalized epilepsy.Epilepsy Res. 2014 Oct;108(8):1267-73. doi: 10.1016/j.eplepsyres.2014.07.001. Epub 2014 Jul 18.
• [6] Synaptojanin 2 is recognized by HLA class II-restricted hairy cell leukemia-specific T cells.Leukemia. 2003 Dec;17(12):2467-73. doi: 10.1038/sj.leu.2403174.
• [7] DNA hypomethylation of Synapsin II CpG islands associates with increased gene expression in bipolar disorder and major depression.BMC Psychiatry. 2016 Aug 11;16(1):286. doi: 10.1186/s12888-016-0989-0.
• [8] A case of nasal low-grade non-intestinal-type adenocarcinoma with aberrant CDX2 expression and a novel SYN2-PPARG gene fusion in a 13-year-old girl.Virchows Arch. 2019 May;474(5):619-623. doi: 10.1007/s00428-019-02524-w. Epub 2019 Jan 21.
• [9] Integration of summary data from GWAS and eQTL studies identified novel causal BMD genes with functional predictions.Bone. 2018 Aug;113:41-48. doi: 10.1016/j.bone.2018.05.012. Epub 2018 May 12.
• [10] Contributions of mTOR Activation-Mediated Upregulation of Synapsin II and Neurite Outgrowth to Hyperalgesia in STZ-Induced Diabetic Rats.ACS Chem Neurosci. 2019 May 15;10(5):2385-2396. doi: 10.1021/acschemneuro.8b00680. Epub 2019 Feb 28.
• [11] Patterns of gene dysregulation in the frontal cortex of patients with HIV encephalitis.J Neuroimmunol. 2004 Dec;157(1-2):163-75. doi: 10.1016/j.jneuroim.2004.08.026.
• [12] An analysis of synapsin II, a neuronal phosphoprotein, in postmortem brain tissue from alcoholic and neuropsychiatrically ill adults and medically ill children and young adults.Arch Gen Psychiatry. 1990 Dec;47(12):1149-56. doi: 10.1001/archpsyc.1990.01810240069011.
• [13] Serum Neuroinflammatory Disease-Induced Central Nervous System Proteins Predict Clinical Onset of Experimental Autoimmune Encephalomyelitis.Front Immunol. 2017 Jul 17;8:812. doi: 10.3389/fimmu.2017.00812. eCollection 2017.
• [14] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [15] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [16] 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.
• [17] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [18] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [19] 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.
• [20] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [21] 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.
• [22] 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.
• [23] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.