Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU5QWFH)

• DOT Name: Complexin-2 (CPLX2)
• Synonyms: Complexin II; CPX II; Synaphin-1
• Gene Name: CPLX2
• Related Disease:
  Attention deficit hyperactivity disorder
  Alzheimer disease
  Bipolar depression
  Bipolar disorder
  Depression
  Early-onset non-syndromic cataract
  Huntington disease
  Myocardial infarction
  Nervous system disease
  Psychotic disorder
  Schizoaffective disorder
  Schizophrenia
• UniProt ID: CPLX2_HUMAN
• Pfam ID: PF05835
• Sequence:
  MDFVMKQALGGATKDMGKMLGGEEEKDPDAQKKEEERQEALRQQEEERKAKHARMEAERE
  KVRQQIRDKYGLKKKEEKEAEEKAALEQPCEGSLTRPKKAIPAGCGDEEEEEEESILDTV
  LKYLPGPLQDMFKK
• Function: Negatively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. Positively regulates a late step in exocytosis of various cytoplasmic vesicles, such as synaptic vesicles and other secretory vesicles. Also involved in mast cell exocytosis.
• Tissue Specificity: Nervous system. In hippocampus and cerebellum, expressed mainly by excitatory neurons. Down-regulated in brain cortex from patients suffering from Huntington disease, bipolar disorder or major depression. Down-regulated in cerebellum from patients with schizophrenia.
• KEGG Pathway: Sy.ptic vesicle cycle (hsa04721)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Attention deficit hyperactivity disorder	DISL8MX9	Definitive	Genetic Variation	[1]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[2]
Bipolar depression	DISA75FU	Strong	Biomarker	[3]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[3]
Depression	DIS3XJ69	Strong	Altered Expression	[4]
Early-onset non-syndromic cataract	DIS4VPS0	Strong	Genetic Variation	[5]
Huntington disease	DISQPLA4	Strong	Biomarker	[4]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[6]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[4]
Psychotic disorder	DIS4UQOT	Strong	Biomarker	[3]
Schizoaffective disorder	DISLBW6B	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[7]

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 Complexin-2 (CPLX2).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Complexin-2 (CPLX2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Complexin-2 (CPLX2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Complexin-2 (CPLX2).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Complexin-2 (CPLX2).	[11]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Complexin-2 (CPLX2).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Complexin-2 (CPLX2).	[13]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Complexin-2 (CPLX2).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Complexin-2 (CPLX2).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Complexin-2 (CPLX2).	[17]

References

• [1] Genome-wide association study of inattention and hyperactivity-impulsivity measured as quantitative traits.Twin Res Hum Genet. 2013 Apr;16(2):560-74. doi: 10.1017/thg.2013.12.
• [2] The Proteome of the Dentate Terminal Zone of the Perforant Path Indicates Presynaptic Impairment in Alzheimer Disease.Mol Cell Proteomics. 2020 Jan;19(1):128-141. doi: 10.1074/mcp.RA119.001737. Epub 2019 Nov 7.
• [3] Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium.Mol Psychiatry. 2004 Jun;9(6):609-20, 544. doi: 10.1038/sj.mp.4001471.
• [4] Clorgyline-mediated reversal of neurological deficits in a Complexin 2 knockout mouse.Hum Mol Genet. 2010 Sep 1;19(17):3402-12. doi: 10.1093/hmg/ddq252. Epub 2010 Jun 28.
• [5] Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract.Hum Mol Genet. 2014 Nov 15;23(22):6119-28. doi: 10.1093/hmg/ddu315. Epub 2014 Jun 20.
• [6] Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.Atherosclerosis. 2011 Mar;215(1):145-52. doi: 10.1016/j.atherosclerosis.2010.12.005. Epub 2010 Dec 15.
• [7] Complexin2 modulates working memory-related neural activity in patients with schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2015 Mar;265(2):137-45. doi: 10.1007/s00406-014-0550-4. Epub 2014 Oct 9.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [12] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [17] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.