Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJR84YR)

• DOT Name: Uncharacterized protein C21orf58 (C21ORF58)
• Gene Name: C21ORF58
• Related Disease: Adenocarcinoma
• UniProt ID: CU058_HUMAN
• Pfam ID: PF15248
• Sequence:
  MARSRLPATSLRKPWKLDRQKLPSPDSGHSLLCGWSPGGKARPAGNTGAWAPAEQFFPAS
  NRTREGGGLWPPLPLQSSPAAPTMLDSSAAEQVTRLTLKLLGQKLEQERQNVEGGPEGLH
  LEPGNEDRPDDALQTALKRRRDLLQRLREQHLLDELSRAQAWSGPSRGALGSALPPELPP
  TGILPTASPSPLAPDPPRIILPTVPQPPATIIQQLPQQPLIAQIPPPQAFPTQRSGSIKE
  DMVELLLLQNAQVHQLVLQNWMLKALPPALQDPPHVPPRVPRAARPRLPAVHHHHHHHHA
  VWPPGAATVLQPAPSLWTPGPP
• Tissue Specificity: Expressed in skin and fetal lung.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[1]

2 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 C21orf58 (C21ORF58).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Uncharacterized protein C21orf58 (C21ORF58).	[12]

11 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 Uncharacterized protein C21orf58 (C21ORF58).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Uncharacterized protein C21orf58 (C21ORF58).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Uncharacterized protein C21orf58 (C21ORF58).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Uncharacterized protein C21orf58 (C21ORF58).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Uncharacterized protein C21orf58 (C21ORF58).	[6]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Uncharacterized protein C21orf58 (C21ORF58).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Uncharacterized protein C21orf58 (C21ORF58).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 affects the expression of Uncharacterized protein C21orf58 (C21ORF58).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Uncharacterized protein C21orf58 (C21ORF58).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Uncharacterized protein C21orf58 (C21ORF58).	[11]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Uncharacterized protein C21orf58 (C21ORF58).	[13]

References

• [1] Isolation and characterization of human lung cancer antigens by serological screening with autologous antibodies.Cancer Lett. 2011 Feb 1;301(1):57-62. doi: 10.1016/j.canlet.2010.10.024. Epub 2010 Nov 20.
• [2] 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.
• [3] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] 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.
• [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] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.