Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGU44V9)

• DOT Name: Protein FAM32A (FAM32A)
• Synonyms: Ovarian tumor-associated gene 12; OTAG-12
• Gene Name: FAM32A
• Related Disease:
  Epithelial ovarian cancer
  Ovarian neoplasm
• UniProt ID: FA32A_HUMAN
• PDB ID: 6QDV; 7W5A; 7W5B; 8C6J
• Pfam ID: PF08555
• Sequence:
  MEAYEQVQKGPLKLKGVAELGVTKRKKKKKDKDKAKLLEAMGTSKKNEEEKRRGLDKRTP
  AQAAFEKMQEKRQMERILKKASKTHKQRVEDFNRHLDTLTEHYDIPKVSWTK
• Function: Isoform 1, but not isoform 2 or isoform 3, may induce G2 arrest and apoptosis. May also increase cell sensitivity to apoptotic stimuli.
• Tissue Specificity: Expressed in ovary, with isoform 1 being predominant.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Limited	Altered Expression	[1]
Ovarian neoplasm	DISEAFTY	Limited	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Protein FAM32A (FAM32A).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein FAM32A (FAM32A).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein FAM32A (FAM32A).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein FAM32A (FAM32A).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein FAM32A (FAM32A).	[6]
Selenium	DM25CGV	Approved	Selenium increases the expression of Protein FAM32A (FAM32A).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein FAM32A (FAM32A).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein FAM32A (FAM32A).	[10]

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 increases the methylation of Protein FAM32A (FAM32A).	[8]

References

• [1] Anti-proliferative and pro-apoptotic actions of a novel human and mouse ovarian tumor-associated gene OTAG-12: downregulation, alternative splicing and drug sensitization.Oncogene. 2011 Jun 23;30(25):2874-87. doi: 10.1038/onc.2011.11. Epub 2011 Feb 21.
• [2] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.