Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0MBUK5)

• DOT Name: Synaptogyrin-1 (SYNGR1)
• Gene Name: SYNGR1
• Related Disease:
  Psoriasis
  Acute myelogenous leukaemia
  Alzheimer disease
  Anxiety
  Anxiety disorder
  Depression
  Primary biliary cholangitis
  Bipolar disorder
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Schizophrenia
• UniProt ID: SNG1_HUMAN
• PDB ID: 8A6M
• Pfam ID: PF01284
• Sequence:
  MEGGAYGAGKAGGAFDPYTLVRQPHTILRVVSWLFSIVVFGSIVNEGYLNSASEGEEFCI
  YNRNPNACSYGVAVGVLAFLTCLLYLALDVYFPQISSVKDRKKAVLSDIGVSAFWAFLWF
  VGFCYLANQWQVSKPKDNPLNEGTDAARAAIAFSFFSIFTWAGQAVLAFQRYQIGADSAL
  FSQDYMDPSQDSSMPYAPYVEPTGPDPAGMGGTYQQPANTFDTEPQGYQSQGY
• Function: May play a role in regulated exocytosis. Modulates the localization of synaptophysin/SYP into synaptic-like microvesicles and may therefore play a role in synaptic-like microvesicle formation and/or maturation. Involved in the regulation of short-term and long-term synaptic plasticity.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Psoriasis	DIS59VMN	Definitive	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Anxiety	DISIJDBA	Strong	Biomarker	[4]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[4]
Depression	DIS3XJ69	Strong	Biomarker	[4]
Primary biliary cholangitis	DIS43E0O	Strong	Genetic Variation	[1]
Bipolar disorder	DISAM7J2	Limited	Autosomal dominant	[5]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[6]
Systemic lupus erythematosus	DISI1SZ7	Limited	Biomarker	[7]
Schizophrenia	DISSRV2N	No Known	Unknown	[8]

19 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 Synaptogyrin-1 (SYNGR1).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Synaptogyrin-1 (SYNGR1).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Synaptogyrin-1 (SYNGR1).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Synaptogyrin-1 (SYNGR1).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Synaptogyrin-1 (SYNGR1).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Synaptogyrin-1 (SYNGR1).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Synaptogyrin-1 (SYNGR1).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Synaptogyrin-1 (SYNGR1).	[17]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Synaptogyrin-1 (SYNGR1).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Synaptogyrin-1 (SYNGR1).	[19]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Synaptogyrin-1 (SYNGR1).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Synaptogyrin-1 (SYNGR1).	[20]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Synaptogyrin-1 (SYNGR1).	[21]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Synaptogyrin-1 (SYNGR1).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Synaptogyrin-1 (SYNGR1).	[20]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Synaptogyrin-1 (SYNGR1).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Synaptogyrin-1 (SYNGR1).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Synaptogyrin-1 (SYNGR1).	[26]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Synaptogyrin-1 (SYNGR1).	[27]

2 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 Synaptogyrin-1 (SYNGR1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Synaptogyrin-1 (SYNGR1).	[24]

References

• [1] Allele-specific transcription factor binding to common and rare variants associated with disease and gene expression.Hum Genet. 2016 May;135(5):485-497. doi: 10.1007/s00439-016-1654-x. Epub 2016 Mar 18.
• [2] Discovery of epigenetically silenced genes in acute myeloid leukemias.Leukemia. 2007 May;21(5):1026-34. doi: 10.1038/sj.leu.2404611. Epub 2007 Mar 1.
• [3] 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.
• [4] Expression and significance of phosphodiesterase 4B gene in peripheral blood of patients with oral lichen planus.Int J Dermatol. 2019 Mar;58(3):302-310. doi: 10.1111/ijd.14203. Epub 2018 Sep 19.
• [5] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [6] Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.Hum Mol Genet. 2019 Mar 1;28(5):858-874. doi: 10.1093/hmg/ddy395.
• [7] High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry.Nat Genet. 2016 Mar;48(3):323-30. doi: 10.1038/ng.3496. Epub 2016 Jan 25.
• [8] Identification of rare mutations of synaptogyrin 1 gene in patients with schizophrenia. J Psychiatr Res. 2007 Dec;41(12):1027-31. doi: 10.1016/j.jpsychires.2006.08.010. Epub 2006 Oct 17.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] 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.
• [11] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [12] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [13] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [14] 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.
• [15] 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.
• [16] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [17] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [18] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [19] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [20] 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.
• [21] 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.
• [22] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [23] 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.
• [24] 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.
• [25] 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.
• [26] 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.
• [27] 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.