Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE8VSSO)

• DOT Name: Coiled-coil domain-containing protein 66 (CCDC66)
• Gene Name: CCDC66
• Related Disease:
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Inherited retinal dystrophy
  Lung adenocarcinoma
  Retinitis pigmentosa
  Retinopathy
  Acute myelogenous leukaemia
  Gastric cancer
  Stomach cancer
  Hirschsprung disease
• UniProt ID: CCD66_HUMAN
• Pfam ID: PF15236
• Sequence:
  MNLGDGLKLETELLDGKTKLILSPYEHKSKISVKMGNKAKIAKCPLRTKTGHILKSTQDT
  CIGSEKLLQKKPVGSETSQAKGEKNGMTFSSTKDLCKQCIDKDCLHIQKEISPATPNMQK
  TRNTVNTSLVGKQKPHKKHITAENMKSSLVCLTQDQLQQILMTVNQGNRSLSLTENGKEA
  KSQYSLYLNSISNQPKDENIMGLFKKTEMVSSVPAENKSVLNEHQETSKQCEQKIAIENE
  WKPADIFSTLGERECDRSSLEAKKAQWRKELDEQVALKKKEKEVSEKWNDPWKKSESDKI
  IWEKHQILDQSRETVLLEHPFSAVKQELQRKWIEELNKQIEDDRQRKIEEKIIYSKGEEH
  DRWAMHFDSLKSYPGSQSQLFSQSTHKQPEYFCVSPDTQELADVSSVCTPTTGSQVEPSE
  EEHIAKPIKDVVMANSKKTNFLRSMTALLDPAQIEERDRRRQKQLEHQKAITAQVEEKRR
  KKQLEEEQRKKEEQEEELRLAQEREEMQKQYEEDILKQKQKEEIMTLKTNELFQTMQRAQ
  ELAQRLKQEQRIRELAQKGHDTSRLIKNLGVDTIQMEYNASNISNSRHDSDEISGKMNTY
  MNSTTSKKDTGVQTDDLNIGIFTNAESHCGSLMERDITNCSSPEISAELIGQFSTKKNKQ
  ELTQDKGASLEKENNRCNDQCNQFTRIEKQTKHMKKYPKRPDWNINKPPKRYIPASEKYP
  KQLQKQREEKKVRRQMELLHLVEKNNPGHLSQNRGISPEIFHSSHQETESKLRWHLVKKE
  EEPLNIHSFSKERSPSSPVPVVKNRTQQTQNTLHLPLKNSSYERENLISGSNQTELSSGI
  SESSHFIPYVRTNEIYYLDPDAPLSGPSTQDPQYQNSQDCGQKRQLFDSDCVRDPLLNPN
  MVKNRDRQQAILKGLSELRQGLLQKQKELESSLLPLAENQEESFGSSF
• Function: Microtubule-binding protein required for ciliogenesis. May function in ciliogenesis by mediating the transport of proteins like BBS4 to the cilium, but also through the organization of the centriolar satellites. Plays a role in retina morphogenesis and/or homeostasis.
• Tissue Specificity: Widely expressed (at protein level) . Expressed in retina, mainly in photoreceptors but also in outer plexiform and ganglion cell layers (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Inherited retinal dystrophy	DISGGL77	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[4]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[5]
Retinopathy	DISB4B0F	Strong	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[6]
Gastric cancer	DISXGOUK	Disputed	Biomarker	[7]
Stomach cancer	DISKIJSX	Disputed	Biomarker	[7]
Hirschsprung disease	DISUUSM1	Limited	Altered Expression	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Coiled-coil domain-containing protein 66 (CCDC66).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Coiled-coil domain-containing protein 66 (CCDC66).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Coiled-coil domain-containing protein 66 (CCDC66).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coiled-coil domain-containing protein 66 (CCDC66).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Coiled-coil domain-containing protein 66 (CCDC66).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Coiled-coil domain-containing protein 66 (CCDC66).	[13]

References

• [1] Noncoding Effects of Circular RNA CCDC66 Promote Colon Cancer Growth and Metastasis.Cancer Res. 2017 May 1;77(9):2339-2350. doi: 10.1158/0008-5472.CAN-16-1883. Epub 2017 Mar 1.
• [2] Plasma circular RNA panel acts as a novel diagnostic biomarker for colorectal cancer.Clin Biochem. 2019 Dec;74:60-68. doi: 10.1016/j.clinbiochem.2019.10.012. Epub 2019 Oct 26.
• [3] Genome-wide linkage and sequence analysis challenge CCDC66 as a human retinal dystrophy candidate gene and support a distinct NMNAT1-related fundus phenotype. Clin Genet. 2018 Jan;93(1):149-154. doi: 10.1111/cge.13022. Epub 2017 May 9.
• [4] The role of HGF-MET pathway and CCDC66 cirRNA expression in EGFR resistance and epithelial-to-mesenchymal transition of lung adenocarcinoma cells.J Hematol Oncol. 2018 May 31;11(1):74. doi: 10.1186/s13045-018-0557-9.
• [5] Ccdc66 null mutation causes retinal degeneration and dysfunction.Hum Mol Genet. 2011 Sep 15;20(18):3620-31. doi: 10.1093/hmg/ddr282. Epub 2011 Jun 16.
• [6] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [7] Circ-CCDC66 accelerates proliferation and invasion of gastric cancer via binding to miRNA-1238-3p.Eur Rev Med Pharmacol Sci. 2019 May;23(10):4164-4172. doi: 10.26355/eurrev_201905_17919.
• [8] Circular RNA CCDC66 targets DCX to regulate cell proliferation and migration by sponging miR-488-3p in Hirschsprung's disease.J Cell Physiol. 2019 Jul;234(7):10576-10587. doi: 10.1002/jcp.27733. Epub 2018 Nov 15.
• [9] 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.
• [10] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [11] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [12] 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.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.