Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ3AGSQ)

• DOT Name: Coiled-coil domain-containing protein 34 (CCDC34)
• Synonyms: Renal carcinoma antigen NY-REN-41
• Gene Name: CCDC34
• Related Disease:
  Advanced cancer
  Bladder cancer
  Cervical cancer
  Cervical carcinoma
  Esophageal squamous cell carcinoma
  Pancreatic adenocarcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adult lymphoma
  Colorectal carcinoma
  Lymphoma
  Neoplasm
  Pediatric lymphoma
  Small lymphocytic lymphoma
  Spermatogenic failure 76
• UniProt ID: CCD34_HUMAN
• Pfam ID: PF13904
• Sequence:
  MWAAGRWGPTFPSSYAGFSADCRPRSRPSSDSCSVPMTGARGQGLEVVRSPSPPLPLSCS
  NSTRSLLSPLGHQSFQFDEDDGDGEDEEDVDDEEDVDEDAHDSEAKVASLRGMELQGCAS
  TQVESENNQEEQKQVRLPESRLTPWEVWFIGKEKEERDRLQLKALEELNQQLEKRKEMEE
  REKRKIIAEEKHKEWVQKKNEQKRKEREQKINKEMEEKAAKELEKEYLQEKAKEKYQEWL
  KKKNAEECERKKKEKEKEKQQQAEIQEKKEIAEKKFQEWLENAKHKPRPAAKSYGYANGK
  LTGFYSGNSYPEPAFYNPIPWKPIHMPPPKEAKDLSGRKSKRPVISQPHKSSSLVIHKAR
  SNLCLGTLCRIQR
• Function: Involved in spermatogenesis. Has a probable role in anterograde intraflagellar transport which is essential for the formation of sperm flagella.
• Tissue Specificity: Expressed in sperm.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Bladder cancer	DISUHNM0	Strong	Biomarker	[2]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[1]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[3]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Altered Expression	[4]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[2]
Adult lymphoma	DISK8IZR	Limited	Altered Expression	[5]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[5]
Lymphoma	DISN6V4S	Limited	Altered Expression	[5]
Neoplasm	DISZKGEW	Limited	Altered Expression	[5]
Pediatric lymphoma	DIS51BK2	Limited	Altered Expression	[5]
Small lymphocytic lymphoma	DIS30POX	Limited	Altered Expression	[5]
Spermatogenic failure 76	DISIC9GG	Limited	Unknown	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[12]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[13]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[19]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[20]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Coiled-coil domain-containing protein 34 (CCDC34).	[21]

References

• [1] High Expression of CCDC34 Is Associated with Poor Survival in Cervical Cancer Patients.Med Sci Monit. 2018 Nov 20;24:8383-8390. doi: 10.12659/MSM.913346.
• [2] CCDC34 is up-regulated in bladder cancer and regulates bladder cancer cell proliferation, apoptosis and migration.Oncotarget. 2015 Sep 22;6(28):25856-67. doi: 10.18632/oncotarget.4624.
• [3] Overexpression of Coiled-Coil Domain-Containing Protein 34 (CCDC34) and its Correlation with Angiogenesis in Esophageal Squamous Cell Carcinoma.Med Sci Monit. 2018 Feb 3;24:698-705. doi: 10.12659/msm.908335.
• [4] Expression of Coiled-Coil Domain Containing 34 (CCDC34) and its Prognostic Significance in Pancreatic Adenocarcinoma.Med Sci Monit. 2017 Dec 19;23:6012-6018. doi: 10.12659/msm.907951.
• [5] Overexpression of CCDC34 in colorectal cancer and its involvement in tumor growth, apoptosis and invasion.Mol Med Rep. 2018 Jan;17(1):465-473. doi: 10.3892/mmr.2017.7860. Epub 2017 Oct 24.
• [6] Homozygous mutations in CCDC34 cause male infertility with oligoasthenoteratozoospermia in humans and mice. J Med Genet. 2022 Jul;59(7):710-718. doi: 10.1136/jmedgenet-2021-107919. Epub 2021 Aug 4.
• [7] 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.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [12] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [13] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [14] 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.
• [15] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [16] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [17] 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.
• [18] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [20] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [21] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.