Details of Drug Off-Target (DOT)

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

• DOT Name: Coiled-coil domain-containing protein 62 (CCDC62)
• Synonyms: Protein TSP-NY; Protein aaa
• Gene Name: CCDC62
• Related Disease:
  Advanced cancer
  Gastric cancer
  Serum sickness
  Stomach cancer
  Testicular cancer
  Male infertility
  Prion disease
  Parkinson disease
  Essential tremor
  Parkinsonian disorder
• UniProt ID: CCD62_HUMAN
• Sequence:
  MNPPAAFLAGRQNIGSEVEISTIEKQRKELQLLIGELKDRDKELNDMVAVHQQQLLSWEE
  DRQKVLTLEERCSKLEGELHKRTEIIRSLTKKVKALESNQMECQTALQKTQLQLQEMAQK
  ATHSSLLSEDLEARNETLSNTLVELSAQVGQLQAREQALTTMIKLKDKDIIEAVNHIADC
  SGKFKMLEHALRDAKMAETCIVKEKQDYKQKLKALKIEVNKLKEDLNEKTTENNEQREEI
  IRLKQEKSCLHDELLFTVEREKRKDELLNIAKSKQERTNSELHNLRQIYVKQQSDLQFLN
  FNVENSQELIQMYDSKMEESKALDSSRDMCLSDLENNHPKVDIKREKNQKSLFKDQKFEA
  MLVQQNRSDKSSCDECKEKKQQIDTVFGEKSVITLSSIFTKDLVEKHNLPWSLGGKTQIE
  PENKITLCKIHTKSPKCHGTGVQNEGKQPSETPTLSDEKQWHDVSVYLGLTNCPSSKHPE
  KLDVECQDQMERSEISCCQKNEACLGESGMCDSKCCHPSNFIIEAPGHMSDVEWMSIFKP
  SKMQRIVRLKSGCTCSESICGTQHDSPASELIAIQDSHSLGSSKSALREDETESSSNKKN
  SPTSLLIYKDAPAFNEKASIVLPSQDDFSPTSKLQRLLAESRQMVTDLELSTLLPISHEN
  LTGSATNKSEVPEESAQKNTFVSY
• Function: Nuclear receptor coactivator that can enhance preferentially estrogen receptors ESR1 and ESR2 transactivation. Modulates also progesterone/PGR, glucocorticoid/NR3C1 and androgen/AR receptors transactivation, although at lower level; little effect on vitamin D receptor/VDR. Required for normal spermiogenesis. It probably plays a role in acrosome formation.
• Tissue Specificity: Highly expressed in adult testis. Expressed in both prostate epithelial and stromal cells, with predominant expression in epithelial cells (at protein level) . Not detected in prostate by RT-PCR . Overexpressed in various cancers.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Gastric cancer	DISXGOUK	Definitive	Altered Expression	[1]
Serum sickness	DIS0MRKJ	Definitive	Biomarker	[1]
Stomach cancer	DISKIJSX	Definitive	Altered Expression	[1]
Testicular cancer	DIS6HNYO	Definitive	Biomarker	[1]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[2]
Prion disease	DISOUMB0	Strong	Genetic Variation	[3]
Parkinson disease	DISQVHKL	moderate	Genetic Variation	[4]
Essential tremor	DIS7GBKQ	Disputed	Biomarker	[5]
Parkinsonian disorder	DISHGY45	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Coiled-coil domain-containing protein 62 (CCDC62).	[7]
Fenfluramine	DM0762O	Phase 3	Fenfluramine increases the expression of Coiled-coil domain-containing protein 62 (CCDC62).	[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 Coiled-coil domain-containing protein 62 (CCDC62).	[9]

References

• [1] Identification of CCDC62-2 as a novel cancer/testis antigen and its immunogenicity.Int J Cancer. 2009 May 15;124(10):2347-52. doi: 10.1002/ijc.24220.
• [2] A nonsense mutation in Ccdc62 gene is responsible for spermiogenesis defects and male infertility in repro29/repro29 mice.Biol Reprod. 2017 Mar 1;96(3):587-597. doi: 10.1095/biolreprod.116.141408.
• [3] Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP.Hum Mol Genet. 2012 Apr 15;21(8):1897-906. doi: 10.1093/hmg/ddr607. Epub 2011 Dec 30.
• [4] A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci.Nat Genet. 2017 Oct;49(10):1511-1516. doi: 10.1038/ng.3955. Epub 2017 Sep 11.
• [5] Genetics of Parkinson's disease and essential tremor.Curr Opin Neurol. 2011 Aug;24(4):318-23. doi: 10.1097/WCO.0b013e3283484b87.
• [6] Association of Parkinson disease risk loci with mild parkinsonian signs in older persons.JAMA Neurol. 2014 Apr;71(4):429-35. doi: 10.1001/jamaneurol.2013.6222.
• [7] 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.
• [8] Fenfluramine-induced gene dysregulation in human pulmonary artery smooth muscle and endothelial cells. Pulm Circ. 2011 Jul-Sep;1(3):405-18. doi: 10.4103/2045-8932.87310.
• [9] 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.