Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU27AN5)

• DOT Name: BTB/POZ domain-containing protein KCTD18 (KCTD18)
• Gene Name: KCTD18
• Related Disease: Restless legs syndrome
• UniProt ID: KCD18_HUMAN
• Pfam ID: PF02214 ; PF19321
• Sequence:
  MEGHKAEEEVLDVLRLNVGGCIYTARRESLCRFKDSMLASMFSGRFPLKTDESGACVIDR
  DGRLFKYLLDYLHGEVQIPTDEQTRIALQEEADYFGIPYPYSLSDHLANEMETYSLRSNI
  ELKKALTDFCDSYGLVCNKPTVWVLHYLNTSGASCESRIIGVYATKTDGTDAIEKQLGGR
  IHSKGIFKREAGNNVQYIWSYYSVAELKKMMDAFDAWEGKGVSYWRVPHELIECWTLEER
  PLLGSLRHMAPIRKRRLITFNEADESVNYKTGPKPVRFLGPSTSTQIKVKNSASVTVSPA
  SAIQTSAGATANRFQSGSRRKAAQRSAPSRATALVGTGAPGHPQASPGAASAENGGTHLP
  PAKVLLSDKKPTPQRVIKLKRTPLCATAPCLPSPTATRQANSLKPLPGEAARALGVRTEN
  GKNKGN

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Restless legs syndrome	DISNWY00	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of BTB/POZ domain-containing protein KCTD18 (KCTD18).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of BTB/POZ domain-containing protein KCTD18 (KCTD18).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of BTB/POZ domain-containing protein KCTD18 (KCTD18).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of BTB/POZ domain-containing protein KCTD18 (KCTD18).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of BTB/POZ domain-containing protein KCTD18 (KCTD18).	[7]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of BTB/POZ domain-containing protein KCTD18 (KCTD18).	[8]

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 decreases the methylation of BTB/POZ domain-containing protein KCTD18 (KCTD18).	[5]

References

• [1] Fine-mapping of restless legs locus 4 (RLS4) identifies a haplotype over the SPATS2L and KCTD18 genes.J Mol Neurosci. 2013 Mar;49(3):600-5. doi: 10.1007/s12031-012-9891-5. Epub 2012 Oct 2.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [8] 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.