Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAU2Y3S)

• DOT Name: Coiled-coil domain-containing protein 148 (CCDC148)
• Gene Name: CCDC148
• Related Disease:
  Cardiovascular disease
  Restless legs syndrome
• UniProt ID: CC148_HUMAN
• Sequence:
  MCAASASPDNLVFHMKNEMRNIKYKPVDYQQLRALTEAKKLASASAKLKIRKAMLTSKLS
  KEQTLIKQHKQVWWQEYQRLNEVRCKMESEIKSLLNEENIGNECLCDLTNFEQELSEQQC
  TYLKNVINPIQQLRADLKYRQHHTLQHSHPHIEFNSMKVLEEVDFVKKQLKTVFERLRLE
  QQRIENDLSDWSIKILDHSLEEKTNPLSELPIELESLECPYPDLKSSILSEFYKFTQKYQ
  KKLQDFNLQLEDIYRNCQLSEEDHWIYQAILDQYPGDLFGRRTLYLDMLQRYFPHKSRHD
  LVEHEKYCDQYRFAIEQQNILISNWNKNKKDFIQKAVLTLTEACATHEMESMLAKDKKKQ
  QELCADLKAKVRQWRAHQEEVARLEMEISARRREKEEEKEKLWKKKELLQRAEKKKKIKK
  YWAKKKQKWQEMEMRDLQRLEELKKLIAEQSLKDRERVKYRQELLERRLMEKKEVALQEA
  HEDKERARRLEALRKQVAVVAQFDPVRMMSDTMASKARMGIEIEEEFILQKPLFTLNTYN
  EQQIISDPRLRFELALREAGLHRTLYAKEILPKISPQKPPRKDMESTVFKI

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[1]
Restless legs syndrome	DISNWY00	moderate	Genetic Variation	[2]

5 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 Coiled-coil domain-containing protein 148 (CCDC148).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Coiled-coil domain-containing protein 148 (CCDC148).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Coiled-coil domain-containing protein 148 (CCDC148).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Coiled-coil domain-containing protein 148 (CCDC148).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Coiled-coil domain-containing protein 148 (CCDC148).	[9]

2 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 affects the methylation of Coiled-coil domain-containing protein 148 (CCDC148).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Coiled-coil domain-containing protein 148 (CCDC148).	[8]

References

• [1] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [2] Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis.Lancet Neurol. 2017 Nov;16(11):898-907. doi: 10.1016/S1474-4422(17)30327-7.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [6] 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.
• [7] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.