Details of Drug Off-Target (DOT)

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

• DOT Name: Protein CUSTOS (C12ORF43)
• Gene Name: C12ORF43
• Related Disease: Coronary atherosclerosis
• UniProt ID: CSTOS_HUMAN
• Sequence:
  MAAPSGTVSDSESSNSSSDAEELERCREAAMPAWGLEQRPHVAGKPRAGAANSQLSTSQP
  SLRHKVNEHEQDGNELQTTPEFRAHVAKKLGALLDSFITISEAAKEPAKAKVQKVALEDD
  GFRLFFTSVPGGREKEESPQPRRKRQPSSSSEDSDEEWRRCREAAVSASDILQESAIHSP
  GTVEKEAKKKRKLKKKAKKVASVDSAVAATTPTSMATVQKQKSGELNGDQVSLGTKKKKK
  AKKASETSPFPPAKSATAIPAN
• Function: Plays a role in the regulation of Wnt signaling pathway during early development.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[1]

3 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 Protein CUSTOS (C12ORF43).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein CUSTOS (C12ORF43).	[3]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein CUSTOS (C12ORF43).	[5]

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 affects the methylation of Protein CUSTOS (C12ORF43).	[4]

References

• [1] A Single-Nucleotide Polymorphism in C12orf43 Region is Associated with the Risk of Coronary Artery Disease in a Pakistani Cohort.Biochem Genet. 2016 Oct;54(5):676-84. doi: 10.1007/s10528-016-9746-9. Epub 2016 Jun 4.
• [2] 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.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] 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.
• [5] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.