Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWS5V2I)

• DOT Name: Divergent protein kinase domain 1A (DIPK1A)
• Synonyms: Protein FAM69A
• Gene Name: DIPK1A
• Related Disease:
  Diamond-Blackfan anemia
  Mental disorder
  Psychotic disorder
  Myasthenia gravis
• UniProt ID: DIK1A_HUMAN
• Pfam ID: PF12260 ; PF14875
• Sequence:
  MARSLCPGAWLRKPYYLQARFSYVRMKYLFFSWLVVFVGSWIIYVQYSTYTELCRGKDCK
  KIICDKYKTGVIDGPACNSLCVTETLYFGKCLSTKPNNQMYLGIWDNLPGVVKCQMEQAL
  HLDFGTELEPRKEIVLFDKPTRGTTVQKFKEMVYSLFKAKLGDQGNLSELVNLILTVADG
  DKDGQVSLGEAKSAWALLQLNEFLLMVILQDKEHTPKLMGFCGDLYVMESVEYTSLYGIS
  LPWVIELFIPSGFRRSMDQLFTPSWPRKAKIAIGLLEFVEDVFHGPYGNFLMCDTSAKNL
  GYNDKYDLKMVDMRKIVPETNLKELIKDRHCESDLDCVYGTDCRTSCDQSTMKCTSEVIQ
  PNLAKACQLLKDYLLRGAPSEIREELEKQLYSCIALKVTANQMEMEHSLILNNLKTLLWK
  KISYTNDS

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diamond-Blackfan anemia	DISI2SNW	Strong	CausalMutation	[1]
Mental disorder	DIS3J5R8	moderate	Genetic Variation	[2]
Psychotic disorder	DIS4UQOT	moderate	Genetic Variation	[2]
Myasthenia gravis	DISELRCI	Limited	Biomarker	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Divergent protein kinase domain 1A (DIPK1A) affects the response to substance of Vinblastine.	[13]

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 Divergent protein kinase domain 1A (DIPK1A).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Divergent protein kinase domain 1A (DIPK1A).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Divergent protein kinase domain 1A (DIPK1A).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Divergent protein kinase domain 1A (DIPK1A).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Divergent protein kinase domain 1A (DIPK1A).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Divergent protein kinase domain 1A (DIPK1A).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Divergent protein kinase domain 1A (DIPK1A).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Divergent protein kinase domain 1A (DIPK1A).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Divergent protein kinase domain 1A (DIPK1A).	[12]

References

• [1] Target enrichment and high-throughput sequencing of 80 ribosomal protein genes to identify mutations associated with Diamond-Blackfan anaemia. Br J Haematol. 2013 Aug;162(4):530-6. doi: 10.1111/bjh.12397. Epub 2013 May 30.
• [2] A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder.Schizophr Res. 2010 Dec;124(1-3):192-9. doi: 10.1016/j.schres.2010.09.002.
• [3] Profiling of patient-specific myocytes identifies altered gene expression in the ophthalmoplegic subphenotype of myasthenia gravis.Orphanet J Rare Dis. 2019 Jan 29;14(1):24. doi: 10.1186/s13023-019-1003-y.
• [4] 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.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] 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.
• [7] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [8] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.