Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFBVS0P)

• DOT Name: Solute carrier family 35 member G2 (SLC35G2)
• Synonyms: Transmembrane protein 22
• Gene Name: SLC35G2
• Related Disease:
  Clear cell renal carcinoma
  Melanoma
  Renal cell carcinoma
  Mitochondrial complex I deficiency
• UniProt ID: S35G2_HUMAN
• Pfam ID: PF00892
• Sequence:
  MDTSPSRKYPVKKRVKIHPNTVMVKYTSHYPQPGDDGYEEINEGYGNFMEENPKKGLLSE
  MKKKGRAFFGTMDTLPPPTEDPMINEIGQFQSFAEKNIFQSRKMWIVLFGSALAHGCVAL
  ITRLVSDRSKVPSLELIFIRSVFQVLSVLVVCYYQEAPFGPSGYRLRLFFYGVCNVISIT
  CAYTSFSIVPPSNGTTMWRATTTVFSAILAFLLVDEKMAYVDMATVVCSILGVCLVMIPN
  IVDEDNSLLNAWKEAFGYTMTVMAGLTTALSMIVYRSIKEKISMWTALFTFGWTGTIWGI
  STMFILQEPIIPLDGETWSYLIAICVCSTAAFLGVYYALDKFHPALVSTVQHLEIVVAMV
  LQLLVLHIFPSIYDVFGGVIIMISVFVLAGYKLYWRNLRKQDYQEILDSPIK

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[1]
Melanoma	DIS1RRCY	Strong	Biomarker	[2]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[1]
Mitochondrial complex I deficiency	DIS13M7V	Limited	Autosomal recessive	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Solute carrier family 35 member G2 (SLC35G2) affects the response to substance of Topotecan.	[18]

12 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 Solute carrier family 35 member G2 (SLC35G2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Solute carrier family 35 member G2 (SLC35G2).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Solute carrier family 35 member G2 (SLC35G2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Solute carrier family 35 member G2 (SLC35G2).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Solute carrier family 35 member G2 (SLC35G2).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Solute carrier family 35 member G2 (SLC35G2).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Solute carrier family 35 member G2 (SLC35G2).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Solute carrier family 35 member G2 (SLC35G2).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Solute carrier family 35 member G2 (SLC35G2).	[13]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Solute carrier family 35 member G2 (SLC35G2).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Solute carrier family 35 member G2 (SLC35G2).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Solute carrier family 35 member G2 (SLC35G2).	[17]

3 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 decreases the methylation of Solute carrier family 35 member G2 (SLC35G2).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Solute carrier family 35 member G2 (SLC35G2).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Solute carrier family 35 member G2 (SLC35G2).	[14]

References

• [1] Involvement of TMEM22 overexpression in the growth of renal cell carcinoma cells.Oncol Rep. 2009 Feb;21(2):305-12.
• [2] Silencing of Peroxiredoxin 2 and aberrant methylation of 33 CpG islands in putative promoter regions in human malignant melanomas.Cancer Res. 2006 Jun 15;66(12):6080-6. doi: 10.1158/0008-5472.CAN-06-0157.
• [3] 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.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [15] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [16] 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.
• [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] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.