Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ4MG1Q)

• DOT Name: Mitochondrial protein C2orf69 (C2ORF69)
• Gene Name: C2ORF69
• Related Disease: Combined oxidative phosphorylation deficiency 53
• UniProt ID: CB069_HUMAN
• Pfam ID: PF10561
• Sequence:
  MWGFRLLRSPPLLLLLPQLGIGNASSCSQARTMNPGGSGGARCSLSAEVRRRQCLQLSTV
  PGADPQRSNELLLLAAAGEGLERQDLPGDPAKEEPQPPPQHHVLYFPGDVQNYHEIMTRH
  PENYQWENWSLENVATILAHRFPNSYIWVIKCSRMHLHKFSCYDNFVKSNMFGAPEHNTD
  FGAFKHLYMLLVNAFNLSQNSLSKKSLNVWNKDSIASNCRSSPSHTTNGCQGEKVRTCEK
  SDESAMSFYPPSLNDASFTLIGFSKGCVVLNQLLFELKEAKKDKNIDAFIKSIRTMYWLD
  GGHSGGSNTWVTYPEVLKEFAQTGIIVHTHVTPYQVRDPMRSWIGKEHKKFVQILGDLGM
  QVTSQIHFTKEAPSIENHFRVHEVF
• Function: May play a role in the respiratory chain.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Combined oxidative phosphorylation deficiency 53	DISVPP8Z	Strong	Autosomal recessive	[1]

8 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 Mitochondrial protein C2orf69 (C2ORF69).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mitochondrial protein C2orf69 (C2ORF69).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial protein C2orf69 (C2ORF69).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Mitochondrial protein C2orf69 (C2ORF69).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitochondrial protein C2orf69 (C2ORF69).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Mitochondrial protein C2orf69 (C2ORF69).	[9]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Mitochondrial protein C2orf69 (C2ORF69).	[10]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Mitochondrial protein C2orf69 (C2ORF69).	[11]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Mitochondrial protein C2orf69 (C2ORF69).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Mitochondrial protein C2orf69 (C2ORF69).	[7]

References

• [1] C2orf69 mutations disrupt mitochondrial function and cause a multisystem human disorder with recurring autoinflammation. J Clin Invest. 2021 Jun 15;131(12):e143078. doi: 10.1172/JCI143078.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [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] 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.
• [9] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [11] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.