Details of Drug Off-Target (DOT)

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

• DOT Name: Uncharacterized protein C8orf34 (C8ORF34)
• Synonyms: Protein VEST-1
• Gene Name: C8ORF34
• Related Disease:
  Advanced cancer
  Narcolepsy
• UniProt ID: CH034_HUMAN
• Pfam ID: PF17824
• Sequence:
  MSSPLASELSELAALRPGFRLSAPHARVAPRAATHARGRGRASHAGQPRLRSSCPGPSPG
  KRRVVPSGGAQPRVLPALSSRSHLFPMASHPQTRIQAYLEKNKIGPLFEELMTKLITETP
  DQPIPFLIDHLQSKQGNRGQLQRTLSGSAALWAESEKSESKGTRRDFRSYDKPWQLNAKK
  PKKSKSDLAVSNISPPSPDSKSLPRSVEHPKWNWRTKPQSRDFDELNHILQESKKLGKAL
  ENLSRSIAISDELDKETVTFNSSLLRPRVIGEWIGREENDADPLAAEMLQPPIPRSKNDQ
  WESEDSGSSPAGSLKMEPKNKGLKQQQQQHKKLLAAMLSQDSFESIHSPTPSVTEEDIDN
  EDDAMELLEDLNDLRMEGVTTLVPSGSKFNQGRPTYPAEPQAKVTLNICSRCARLQGDNL
  EERTEESLPILHSPDEKIPDSFDSLPGTEEALMEEGDEFEKASKLTGPGEASSGVGHSLK
  NYMEEDESLKQLQVVHQPWILPSDTESEGVEAEQEKRSADLLLCVPCSSCPTLVYSGL

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Irinotecan	DMP6SC2	Approved	Uncharacterized protein C8orf34 (C8ORF34) increases the Drug toxicity ADR of Irinotecan.	[10]

7 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 Uncharacterized protein C8orf34 (C8ORF34).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Uncharacterized protein C8orf34 (C8ORF34).	[4]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Uncharacterized protein C8orf34 (C8ORF34).	[5]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Uncharacterized protein C8orf34 (C8ORF34).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Uncharacterized protein C8orf34 (C8ORF34).	[5]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Uncharacterized protein C8orf34 (C8ORF34).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Uncharacterized protein C8orf34 (C8ORF34).	[9]

2 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 Uncharacterized protein C8orf34 (C8ORF34).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Uncharacterized protein C8orf34 (C8ORF34).	[8]

References

• [1] Cancer risk susceptibility loci in a Swedish population.Oncotarget. 2017 Nov 25;8(66):110300-110310. doi: 10.18632/oncotarget.22687. eCollection 2017 Dec 15.
• [2] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [3] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [4] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [5] 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.
• [6] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] A genome-wide association study for irinotecan-related severe toxicities in patients with advanced non-small-cell lung cancer. Pharmacogenomics J. 2013 Oct;13(5):417-22. doi: 10.1038/tpj.2012.24. Epub 2012 Jun 5.