Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6TFN1O)

• DOT Name: Uncharacterized protein C4orf3 (C4ORF3)
• Synonyms: Hepatitis C virus F protein-transactivated protein 1; HCV F-transactivated protein 1
• Gene Name: C4ORF3
• Related Disease:
  Respiratory syncytial virus infection
  Breast carcinoma
  Dilated cardiomyopathy 1A
  Haemophilia A
  Hemophilia
  Hereditary angioedema
  Lung cancer
  Lung carcinoma
  Myasthenia gravis
  Postmenopausal osteoporosis
  Primary hyperoxaluria type 1
  Advanced cancer
  Breast cancer
  Autism spectrum disorder
  Language disorder
  Neoplasm
  Specific language impairment
• UniProt ID: CD003_HUMAN
• Pfam ID: PF17696
• Sequence:
  MEVDAPGVDGRDGLRERRGFSEGGRQNFDVRPQSGANGLPKHSYWLDLWLFILFDVVVFL
  FVYFLP
• KEGG Pathway: Calcium sig.ling pathway (hsa04020)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Respiratory syncytial virus infection	DIS7FWHY	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Genetic Variation	[3]
Haemophilia A	DIS0RQ2E	Strong	Biomarker	[4]
Hemophilia	DIS1S8P6	Strong	Biomarker	[4]
Hereditary angioedema	DIS8X53J	Strong	Biomarker	[5]
Lung cancer	DISCM4YA	Strong	Biomarker	[6]
Lung carcinoma	DISTR26C	Strong	Biomarker	[6]
Myasthenia gravis	DISELRCI	Strong	Biomarker	[7]
Postmenopausal osteoporosis	DISS0RQZ	Strong	Genetic Variation	[8]
Primary hyperoxaluria type 1	DISS210K	Strong	Biomarker	[9]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[10]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[2]
Autism spectrum disorder	DISXK8NV	Limited	Biomarker	[11]
Language disorder	DISTLKP7	Limited	Biomarker	[11]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]
Specific language impairment	DISEKRML	Limited	Biomarker	[11]

16 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 Uncharacterized protein C4orf3 (C4ORF3).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Uncharacterized protein C4orf3 (C4ORF3).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Uncharacterized protein C4orf3 (C4ORF3).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Uncharacterized protein C4orf3 (C4ORF3).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Uncharacterized protein C4orf3 (C4ORF3).	[16]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Uncharacterized protein C4orf3 (C4ORF3).	[17]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Uncharacterized protein C4orf3 (C4ORF3).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Uncharacterized protein C4orf3 (C4ORF3).	[19]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Uncharacterized protein C4orf3 (C4ORF3).	[20]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Uncharacterized protein C4orf3 (C4ORF3).	[16]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Uncharacterized protein C4orf3 (C4ORF3).	[16]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Uncharacterized protein C4orf3 (C4ORF3).	[16]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Uncharacterized protein C4orf3 (C4ORF3).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Uncharacterized protein C4orf3 (C4ORF3).	[22]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Uncharacterized protein C4orf3 (C4ORF3).	[23]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Uncharacterized protein C4orf3 (C4ORF3).	[24]

References

• [1] A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus.Proc Natl Acad Sci U S A. 2010 May 11;107(19):8800-5. doi: 10.1073/pnas.0912186107. Epub 2010 Apr 26.
• [2] Is axillary lymph node dissection necessary for positive preoperative aspiration cytology lymph node results?.Eur J Surg Oncol. 2020 Apr;46(4 Pt A):504-510. doi: 10.1016/j.ejso.2019.10.043. Epub 2019 Nov 1.
• [3] Comparison of sentinel lymph node biopsy between invasive lobular carcinoma and invasive ductal carcinoma.Breast Cancer. 2018 Sep;25(5):560-565. doi: 10.1007/s12282-018-0852-x. Epub 2018 Mar 13.
• [4] An RNAi therapeutic targeting antithrombin to rebalance the coagulation system and promote hemostasis in hemophilia.Nat Med. 2015 May;21(5):492-7. doi: 10.1038/nm.3847. Epub 2015 Apr 13.
• [5] An investigational RNAi therapeutic targeting Factor XII (ALN-F12) for the treatment of hereditary angioedema.RNA. 2019 Feb;25(2):255-263. doi: 10.1261/rna.068916.118. Epub 2018 Nov 21.
• [6] Bone metastasis target redox-responsive micell for the treatment of lung cancer bone metastasis and anti-bone resorption.Artif Cells Nanomed Biotechnol. 2018;46(sup1):380-391. doi: 10.1080/21691401.2018.1426007. Epub 2018 Jan 16.
• [7] Investigational RNAi Therapeutic Targeting C5 Is Efficacious in Pre-clinical Models of Myasthenia Gravis. Mol Ther Methods Clin Dev. 2019 May 10;13:484-492.
• [8] Clinical characteristics associated with bone mineral density improvement after 1-year alendronate/vitamin d3 or calcitriol treatment: Exploratory results from a phase 3, randomized, controlled trial on postmenopausal osteoporotic women in China.Medicine (Baltimore). 2018 Aug;97(31):e11694. doi: 10.1097/MD.0000000000011694.
• [9] An Investigational RNAi Therapeutic Targeting Glycolate Oxidase Reduces Oxalate Production in Models of Primary Hyperoxaluria.J Am Soc Nephrol. 2017 Feb;28(2):494-503. doi: 10.1681/ASN.2016030338. Epub 2016 Jul 18.
• [10] First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement.Cancer Discov. 2013 Apr;3(4):406-17. doi: 10.1158/2159-8290.CD-12-0429. Epub 2013 Jan 28.
• [11] Language and reading abilities of children with autism spectrum disorders and specific language impairment and their first-degree relatives.Autism Res. 2009 Feb;2(1):22-38. doi: 10.1002/aur.63.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [14] 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.
• [15] 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.
• [16] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [17] 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.
• [18] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [19] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [20] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [21] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [22] 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.
• [23] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [24] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.