Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK4O2C1)

• DOT Name: Uncharacterized protein C3orf38 (C3ORF38)
• Gene Name: C3ORF38
• Related Disease: Schizophrenia
• UniProt ID: CC038_HUMAN
• Pfam ID: PF15008
• Sequence:
  MEMSGLSFSEMEGCRNLLGLLDNDEIMALCDTVTNRLVQPQDRQDAVHAILAYSQSAEEL
  LRRRKVHREVIFKYLATQGIVIPPATEKHNLIQHAKDYWQKQPQLKLKETPEPVTKTEDI
  HLFQQQVKEDKKAEKVDFRRLGEEFCHWFFGLLNSQNPFLGPPQDEWGPQHFWHDVKLRF
  YYNTSEQNVMDYHGAEIVSLRLLSLVKEEFLFLSPNLDSHGLKCASSPHGLVMVGVAGTV
  HRGNTCLGIFEQIFGLIRCPFVENTWKIKFINLKIMGESSLAPGTLPKPSVKFEQSDLEA
  FYNVITVCGTNEVRHNVKQASDSGTGDQV
• Function: May be involved in apoptosis regulation.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Uncharacterized protein C3orf38 (C3ORF38) increases the Hepatotoxicity ADR of Acetaminophen.	[11]
NAPQI	DM8F5LR	Investigative	Uncharacterized protein C3orf38 (C3ORF38) affects the response to substance of NAPQI.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Uncharacterized protein C3orf38 (C3ORF38).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Uncharacterized protein C3orf38 (C3ORF38).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Uncharacterized protein C3orf38 (C3ORF38).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Uncharacterized protein C3orf38 (C3ORF38).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Uncharacterized protein C3orf38 (C3ORF38).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Uncharacterized protein C3orf38 (C3ORF38).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Uncharacterized protein C3orf38 (C3ORF38).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Uncharacterized protein C3orf38 (C3ORF38).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Uncharacterized protein C3orf38 (C3ORF38).	[10]

References

• [1] Genome-wide association study of paliperidone efficacy.Pharmacogenet Genomics. 2017 Jan;27(1):7-18. doi: 10.1097/FPC.0000000000000250.
• [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] 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.
• [5] 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.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [11] Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.