Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN1GGCN)

• DOT Name: Casein kinase I isoform gamma-3 (CSNK1G3)
• Synonyms: CKI-gamma 3; EC 2.7.11.1
• Gene Name: CSNK1G3
• Related Disease: Tourette syndrome
• UniProt ID: KC1G3_HUMAN
• PDB ID: 2CHL; 2IZR; 2IZS; 2IZT; 2IZU; 4G16; 4G17; 4HGL; 4HGS; 6GRO
• EC Number: 2.7.11.1
• Pfam ID: PF12605 ; PF00069
• Sequence:
  MENKKKDKDKSDDRMARPSGRSGHNTRGTGSSSSGVLMVGPNFRVGKKIGCGNFGELRLG
  KNLYTNEYVAIKLEPMKSRAPQLHLEYRFYKQLGSGDGIPQVYYFGPCGKYNAMVLELLG
  PSLEDLFDLCDRTFSLKTVLMIAIQLISRMEYVHSKNLIYRDVKPENFLIGRPGNKTQQV
  IHIIDFGLAKEYIDPETKKHIPYREHKSLTGTARYMSINTHLGKEQSRRDDLEALGHMFM
  YFLRGSLPWQGLKADTLKERYQKIGDTKRATPIEVLCENFPEMATYLRYVRRLDFFEKPD
  YDYLRKLFTDLFDRKGYMFDYEYDWIGKQLPTPVGAVQQDPALSSNREAHQHRDKMQQSK
  NQSADHRAAWDSQQANPHHLRAHLAADRHGGSVQVVSSTNGELNTDDPTAGRSNAPITAP
  TEVEVMDETKCCCFFKRRKRKTIQRHK
• Function: Serine/threonine-protein kinase. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Regulates fast synaptic transmission mediated by glutamate.
• KEGG Pathway: Hedgehog sig.ling pathway (hsa04340)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tourette syndrome	DISX9D54	Limited	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Casein kinase I isoform gamma-3 (CSNK1G3).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Casein kinase I isoform gamma-3 (CSNK1G3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Casein kinase I isoform gamma-3 (CSNK1G3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Casein kinase I isoform gamma-3 (CSNK1G3).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Casein kinase I isoform gamma-3 (CSNK1G3).	[6]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Casein kinase I isoform gamma-3 (CSNK1G3).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Casein kinase I isoform gamma-3 (CSNK1G3).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Casein kinase I isoform gamma-3 (CSNK1G3).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Casein kinase I isoform gamma-3 (CSNK1G3).	[9]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.