Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWZVF89)

• DOT Name: Coiled-coil domain-containing protein 78 (CCDC78)
• Synonyms: hsCCDC78
• Gene Name: CCDC78
• Related Disease:
  Congenital myopathy
  Congenital myopathy with internal nuclei and atypical cores
  Myopathy
  Centronuclear myopathy
• UniProt ID: CCD78_HUMAN
• Pfam ID: PF14739
• Sequence:
  MEHAATTGPRPGPPSRRVENVVLRAKDWLPGAPGGTAVWATSLEAEVPPDLALNKEQQLQ
  ISKELVDIQITTHHLHEQHEAEIFQLKSEILRLESRVLELELRGDGTSQGCAVPVESDPR
  HPRAAAQELRHKAQVPGHSDDHRFQVQPKNTMNPENEQHRLGSGLQGEVKWALEHQEARQ
  QALVTRVATLGRQLQGAREEARAAGQRLATQAVVLCSCQGQLRQAEAENARLQLQLKKLK
  DEYVLRLQHCAWQAVEHADGAGQAPATTALRTFLEATLEDIRAAHRSREQQLARAARSYH
  KRLVDLSRRHEELLVAYRAPGNPQAIFDIASLDLEPLPVPLVTDFSHREDQHGGPGALLS
  SPKKRPGGASQGGTSEPQGLDAASWAQIHQKLRDFSRSTQSWNGSGHSCWSGPRWLKSNF
  LSYRSTWTSTWAGTSTKS
• Function: Component of the deuterosome, a structure that promotes de novo centriole amplification in multiciliated cells that can generate more than 100 centrioles. Deuterosome-mediated centriole amplification occurs in terminally differentiated multiciliated cells (G1/0) and not in S phase. Essential for centriole amplification and is required for CEP152 localization to the deuterosome.
• Tissue Specificity: Expressed primarily in skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital myopathy	DISLSK9G	Strong	Genetic Variation	[1]
Congenital myopathy with internal nuclei and atypical cores	DISVC9AW	Strong	Autosomal dominant	[1]
Myopathy	DISOWG27	Strong	Genetic Variation	[1]
Centronuclear myopathy	DISXBEJO	Limited	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Coiled-coil domain-containing protein 78 (CCDC78).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Coiled-coil domain-containing protein 78 (CCDC78).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Coiled-coil domain-containing protein 78 (CCDC78).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Coiled-coil domain-containing protein 78 (CCDC78).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Coiled-coil domain-containing protein 78 (CCDC78).	[7]

References

• [1] Dominant mutation of CCDC78 in a unique congenital myopathy with prominent internal nuclei and atypical cores. Am J Hum Genet. 2012 Aug 10;91(2):365-71. doi: 10.1016/j.ajhg.2012.06.012. Epub 2012 Jul 19.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] 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.
• [4] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [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] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.