Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8TGV8R)

• DOT Name: BTB/POZ domain-containing protein KCTD2 (KCTD2)
• Synonyms: Potassium channel tetramerization domain-containing protein 2
• Gene Name: KCTD2
• Related Disease:
  Alzheimer disease
  Glioma
• UniProt ID: KCTD2_HUMAN
• Pfam ID: PF02214
• Sequence:
  MAELQLDPAMAGLGGGGGSGVGDGGGPVRGPPSPRPAGPTPRGHGRPAAAVAQPLEPGPG
  PPERAGGGGAARWVRLNVGGTYFVTTRQTLGREPKSFLCRLCCQEDPELDSDKDETGAYL
  IDRDPTYFGPILNYLRHGKLIITKELAEEGVLEEAEFYNIASLVRLVKERIRDNENRTSQ
  GPVKHVYRVLQCQEEELTQMVSTMSDGWKFEQLISIGSSYNYGNEDQAEFLCVVSRELNN
  STNGIVIEPSEKAKILQERGSRM

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]

7 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 BTB/POZ domain-containing protein KCTD2 (KCTD2).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of BTB/POZ domain-containing protein KCTD2 (KCTD2).	[3]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of BTB/POZ domain-containing protein KCTD2 (KCTD2).	[4]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of BTB/POZ domain-containing protein KCTD2 (KCTD2).	[5]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of BTB/POZ domain-containing protein KCTD2 (KCTD2).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of BTB/POZ domain-containing protein KCTD2 (KCTD2).	[7]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of BTB/POZ domain-containing protein KCTD2 (KCTD2).	[8]

References

• [1] ATP5H/KCTD2 locus is associated with Alzheimer's disease risk.Mol Psychiatry. 2014 Jun;19(6):682-7. doi: 10.1038/mp.2013.86. Epub 2013 Jul 16.
• [2] KCTD2, an adaptor of Cullin3 E3 ubiquitin ligase, suppresses gliomagenesis by destabilizing c-Myc.Cell Death Differ. 2017 Apr;24(4):649-659. doi: 10.1038/cdd.2016.151. Epub 2017 Jan 6.
• [3] 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.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [6] 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.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.