Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBLVF8V)

• DOT Name: Semaphorin-3G (SEMA3G)
• Synonyms: Semaphorin sem2
• Gene Name: SEMA3G
• Related Disease:
  Glioma
  Neoplasm
  Nephropathy
  Obesity
• UniProt ID: SEM3G_HUMAN
• Pfam ID: PF00047 ; PF01403
• Sequence:
  MAPSAWAICWLLGGLLLHGGSSGPSPGPSVPRLRLSYRDLLSANRSAIFLGPQGSLNLQA
  MYLDEYRDRLFLGGLDALYSLRLDQAWPDPREVLWPPQPGQREECVRKGRDPLTECANFV
  RVLQPHNRTHLLACGTGAFQPTCALITVGHRGEHVLHLEPGSVESGRGRCPHEPSRPFAS
  TFIDGELYTGLTADFLGREAMIFRSGGPRPALRSDSDQSLLHDPRFVMAARIPENSDQDN
  DKVYFFFSETVPSPDGGSNHVTVSRVGRVCVNDAGGQRVLVNKWSTFLKARLVCSVPGPG
  GAETHFDQLEDVFLLWPKAGKSLEVYALFSTVSAVFQGFAVCVYHMADIWEVFNGPFAHR
  DGPQHQWGPYGGKVPFPRPGVCPSKMTAQPGRPFGSTKDYPDEVLQFARAHPLMFWPVRP
  RHGRPVLVKTHLAQQLHQIVVDRVEAEDGTYDVIFLGTDSGSVLKVIALQAGGSAEPEEV
  VLEELQVFKVPTPITEMEISVKRQMLYVGSRLGVAQLRLHQCETYGTACAECCLARDPYC
  AWDGASCTHYRPSLGKRRFRRQDIRHGNPALQCLGQSQEEEAVGLVAATMVYGTEHNSTF
  LECLPKSPQAAVRWLLQRPGDEGPDQVKTDERVLHTERGLLFRRLSRFDAGTYTCTTLEH
  GFSQTVVRLALVVIVASQLDNLFPPEPKPEEPPARGGLASTPPKAWYKDILQLIGFANLP
  RVDEYCERVWCRGTTECSGCFRSRSRGKQARGKSWAGLELGKKMKSRVHAEHNRTPREVE
  AT
• Function: Has chemorepulsive activities for sympathetic axons. Ligand of NRP2.
• KEGG Pathway: Axon guidance (hsa04360)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Definitive	Altered Expression	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Nephropathy	DISXWP4P	Definitive	Biomarker	[3]
Obesity	DIS47Y1K	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Semaphorin-3G (SEMA3G).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin affects the expression of Semaphorin-3G (SEMA3G).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Semaphorin-3G (SEMA3G).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Semaphorin-3G (SEMA3G).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Semaphorin-3G (SEMA3G).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Semaphorin-3G (SEMA3G).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Semaphorin-3G (SEMA3G).	[11]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Semaphorin-3G (SEMA3G).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Semaphorin-3G (SEMA3G).	[13]
Lindane	DMB8CNL	Approved	Lindane decreases the expression of Semaphorin-3G (SEMA3G).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Semaphorin-3G (SEMA3G).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Semaphorin-3G (SEMA3G).	[16]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Semaphorin-3G (SEMA3G).	[9]

1 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 increases the methylation of Semaphorin-3G (SEMA3G).	[14]

References

• [1] Semaphorin, neuropilin and VEGF expression in glial tumours: SEMA3G, a prognostic marker?.Br J Cancer. 2008 Oct 7;99(7):1153-60. doi: 10.1038/sj.bjc.6604641. Epub 2008 Sep 9.
• [2] Effects of SEMA3G on migration and invasion of glioma cells.Oncol Rep. 2012 Jul;28(1):269-75. doi: 10.3892/or.2012.1796. Epub 2012 May 4.
• [3] A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation.Sci Rep. 2016 May 16;6:25955. doi: 10.1038/srep25955.
• [4] Mechanism of SEMA3G knockdown-mediated attenuation of high-fat diet-induced obesity.J Endocrinol. 2020 Jan;244(1):223-236. doi: 10.1530/JOE-19-0029.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [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] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] 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.
• [12] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] 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.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.