Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJX84RI)

• DOT Name: Synaptogyrin-2 (SYNGR2)
• Synonyms: Cellugyrin
• Gene Name: SYNGR2
• Related Disease:
  Lung adenocarcinoma
  Lung carcinoma
  Advanced cancer
• UniProt ID: SNG2_HUMAN
• Pfam ID: PF01284
• Sequence:
  MESGAYGAAKAGGSFDLRRFLTQPQVVARAVCLVFALIVFSCIYGEGYSNAHESKQMYCV
  FNRNEDACRYGSAIGVLAFLASAFFLVVDAYFPQISNATDRKYLVIGDLLFSALWTFLWF
  VGFCFLTNQWAVTNPKDVLVGADSVRAAITFSFFSIFSWGVLASLAYQRYKAGVDDFIQN
  YVDPTPDPNTAYASYPGASVDNYQQPPFTQNAETTEGYQPPPVY
• Function: May play a role in regulated exocytosis. In neuronal cells, modulates the localization of synaptophysin/SYP into synaptic-like microvesicles and may therefore play a role in the formation and/or the maturation of this vesicles. May also play a role in GLUT4 storage and transport to the plasma membrane; (Microbial infection) May play a role in the assembly of cytoplasmic inclusion bodies required for SFTS phlebovirus replication.
• Tissue Specificity: Ubiquitous; low expression in brain.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[1]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[2]

3 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-2 (SYNGR2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Synaptogyrin-2 (SYNGR2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Synaptogyrin-2 (SYNGR2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Synaptogyrin-2 (SYNGR2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Synaptogyrin-2 (SYNGR2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Synaptogyrin-2 (SYNGR2).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Synaptogyrin-2 (SYNGR2).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Synaptogyrin-2 (SYNGR2).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Synaptogyrin-2 (SYNGR2).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Synaptogyrin-2 (SYNGR2).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Synaptogyrin-2 (SYNGR2).	[13]

References

• [1] Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women.Hum Mol Genet. 2016 Feb 1;25(3):620-9. doi: 10.1093/hmg/ddv494. Epub 2016 Jan 4.
• [2] A six-gene model for differentiating benign from malignant thyroid tumors on the basis of gene expression.Surgery. 2005 Dec;138(6):1050-6; discussion 1056-7. doi: 10.1016/j.surg.2005.09.010.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.