Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLLVHH0)

• DOT Name: Uncharacterized protein C16orf74 (C16ORF74)
• Gene Name: C16ORF74
• Related Disease:
  Matthew-Wood syndrome
  Non-insulin dependent diabetes
  Pancreatic cancer
  Neoplasm
• UniProt ID: CP074_HUMAN
• Pfam ID: PF15366
• Sequence:
  MGLKMSCLKGFQMCVSSSSSSHDEAPVLNDKHLDVPDIIITPPTPTGMMLPRDLGSTVWL
  DETGSCPDDGEIDPEA
• Tissue Specificity: .Not expressed in pancreatic duct cells (at protein level). Abundantly expressed in the pancreas and weakly expressed in the thyroid.; [Isoform 2]: Not expressed in pancreatic duct cells (at protein level). Abundantly expressed in the lymph node and weakly expressed in the stomach, trachea and bone marrow.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[2]
Pancreatic cancer	DISJC981	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Limited	Biomarker	[3]

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 Uncharacterized protein C16orf74 (C16ORF74).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Uncharacterized protein C16orf74 (C16ORF74).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Uncharacterized protein C16orf74 (C16ORF74).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Uncharacterized protein C16orf74 (C16ORF74).	[5]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Uncharacterized protein C16orf74 (C16ORF74).	[6]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Uncharacterized protein C16orf74 (C16ORF74).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Uncharacterized protein C16orf74 (C16ORF74).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Uncharacterized protein C16orf74 (C16ORF74).	[11]

References

• [1] Role of Dimerized C16orf74 in Aggressive Pancreatic Cancer: A Novel Therapeutic Target.Mol Cancer Ther. 2020 Jan;19(1):187-198. doi: 10.1158/1535-7163.MCT-19-0491. Epub 2019 Oct 9.
• [2] Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes.Nat Commun. 2016 Jan 28;7:10531. doi: 10.1038/ncomms10531.
• [3] Molecular targeting of cell-permeable peptide inhibits pancreatic ductal adenocarcinoma cell proliferation.Oncotarget. 2017 Oct 19;8(69):113662-113672. doi: 10.18632/oncotarget.21939. eCollection 2017 Dec 26.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [7] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [8] 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.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] 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.
• [11] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.