Details of Drug Off-Target (DOT)

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

• DOT Name: Synaptogyrin-3 (SYNGR3)
• Gene Name: SYNGR3
• Related Disease:
  Congenital diarrhea 5 with tufting enteropathy
  Alzheimer disease
• UniProt ID: SNG3_HUMAN
• Pfam ID: PF01284
• Sequence:
  MEGASFGAGRAGAALDPVSFARRPQTLLRVASWVFSIAVFGPIVNEGYVNTDSGPELRCV
  FNGNAGACRFGVALGLGAFLACAAFLLLDVRFQQISSVRDRRRAVLLDLGFSGLWSFLWF
  VGFCFLTNQWQRTAPGPATTQAGDAARAAIAFSFFSILSWVALTVKALQRFRLGTDMSLF
  ATEQLSTGASQAYPGYPVGSGVEGTETYQSPPFTETLDTSPKGYQVPAY
• Function: May play a role in regulated exocytosis. May indirectly regulate the activity of the plasma membrane dopamine transporter SLC6A3 and thereby regulate dopamine transport back from the synaptic cleft into the presynaptic terminal.
• Tissue Specificity: Expressed in brain and placenta.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital diarrhea 5 with tufting enteropathy	DISPAMX4	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Synaptogyrin-3 (SYNGR3).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Synaptogyrin-3 (SYNGR3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Synaptogyrin-3 (SYNGR3).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Synaptogyrin-3 (SYNGR3).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Synaptogyrin-3 (SYNGR3).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Synaptogyrin-3 (SYNGR3).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Synaptogyrin-3 (SYNGR3).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Synaptogyrin-3 (SYNGR3).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Synaptogyrin-3 (SYNGR3).	[11]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Synaptogyrin-3 (SYNGR3).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Synaptogyrin-3 (SYNGR3).	[12]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Synaptogyrin-3 (SYNGR3).	[13]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine decreases the expression of Synaptogyrin-3 (SYNGR3).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Synaptogyrin-3 (SYNGR3).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Synaptogyrin-3 (SYNGR3).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Synaptogyrin-3 (SYNGR3).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Synaptogyrin-3 (SYNGR3).	[7]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Synaptogyrin-3 (SYNGR3).	[17]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of Synaptogyrin-3 (SYNGR3).	[18]

References

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• [2] Age-related changes in gene expression are accelerated in Alzheimer's disease.Synapse. 2011 Sep;65(9):971-4. doi: 10.1002/syn.20933. Epub 2011 Apr 11.
• [3] 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.
• [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] 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.
• [7] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [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] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] 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.
• [13] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [16] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [17] 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.
• [18] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.