Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZEG7K0)

• DOT Name: Conserved oligomeric Golgi complex subunit 5 (COG5)
• Synonyms: COG complex subunit 5; 13S Golgi transport complex 90 kDa subunit; GTC-90; Component of oligomeric Golgi complex 5; Golgi transport complex 1
• Gene Name: COG5
• Related Disease:
  Alzheimer disease
  Atrial fibrillation
  COG5-congenital disorder of glycosylation
  Congenital disorder of glycosylation
  Enterovirus infection
  Friedreich's ataxia
  Osteoarthritis
  Uterine fibroids
  Coronary heart disease
  Familial atrial fibrillation
• UniProt ID: COG5_HUMAN
• Pfam ID: PF20649 ; PF10392
• Sequence:
  MGWVGGRRRDSASPPGRSRSAADDINPAPANMEGGGGSVAVAGLGARGSGAAAATVRELL
  QDGCYSDFLNEDFDVKTYTSQSIHQAVIAEQLAKLAQGISQLDRELHLQVVARHEDLLAQ
  ATGIESLEGVLQMMQTRIGALQGAVDRIKAKIVEPYNKIVARTAQLARLQVACDLLRRII
  RILNLSKRLQGQLQGGSREITKAAQSLNELDYLSQGIDLSGIEVIENDLLFIARARLEVE
  NQAKRLLEQGLETQNPTQVGTALQVFYNLGTLKDTITSVVDGYCATLEENINSALDIKVL
  TQPSQSAVRGGPGRSTMPTPGNTAALRASFWTNMEKLMDHIYAVCGQVQHLQKVLAKKRD
  PVSHICFIEEIVKDGQPEIFYTFWNSVTQALSSQFHMATNSSMFLKQAFEGEYPKLLRLY
  NDLWKRLQQYSQHIQGNFNASGTTDLYVDLQHMEDDAQDIFIPKKPDYDPEKALKDSLQP
  YEAAYLSKSLSRLFDPINLVFPPGGRNPPSSDELDGIIKTIASELNVAAVDTNLTLAVSK
  NVAKTIQLYSVKSEQLLSTQGDASQVIGPLTEGQRRNVAVVNSLYKLHQSVTKVVSSQSS
  FPLAAEQTIISALKAIHALMENAVQPLLTSVGDAIEAIIITMHQEDFSGSLSSSGKPDVP
  CSLYMKELQGFIARVMSDYFKHFECLDFVFDNTEAIAQRAVELFIRHASLIRPLGEGGKM
  RLAADFAQMELAVGPFCRRVSDLGKSYRMLRSFRPLLFQASEHVASSPALGDVIPFSIII
  QFLFTRAPAELKSPFQRAEWSHTRFSQWLDDHPSEKDRLLLIRGALEAYVQSVRSREGKE
  FAPVYPIMVQLLQKAMSALQ
• Function: Required for normal Golgi function.
• Reactome Pathway:
  Intra-Golgi traffic (R-HSA-6811438)
  Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)
  COPI-mediated anterograde transport (R-HSA-6807878)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[2]
COG5-congenital disorder of glycosylation	DISZD56L	Strong	Autosomal recessive	[3]
Congenital disorder of glycosylation	DIS400QP	Strong	Genetic Variation	[4]
Enterovirus infection	DISH2UDP	Strong	Biomarker	[5]
Friedreich's ataxia	DIS5DV35	Strong	Biomarker	[6]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[7]
Uterine fibroids	DISBZRMJ	Strong	Biomarker	[8]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[9]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Conserved oligomeric Golgi complex subunit 5 (COG5).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Conserved oligomeric Golgi complex subunit 5 (COG5).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Conserved oligomeric Golgi complex subunit 5 (COG5).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Conserved oligomeric Golgi complex subunit 5 (COG5).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Conserved oligomeric Golgi complex subunit 5 (COG5).	[14]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Conserved oligomeric Golgi complex subunit 5 (COG5).	[15]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Conserved oligomeric Golgi complex subunit 5 (COG5).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Conserved oligomeric Golgi complex subunit 5 (COG5).	[17]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Conserved oligomeric Golgi complex subunit 5 (COG5).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Conserved oligomeric Golgi complex subunit 5 (COG5).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Conserved oligomeric Golgi complex subunit 5 (COG5).	[19]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Conserved oligomeric Golgi complex subunit 5 (COG5).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Conserved oligomeric Golgi complex subunit 5 (COG5).	[20]

References

• [1] Alzheimer's Disease Assessment Scale-Cognitive subscale variants in mild cognitive impairment and mild Alzheimer's disease: change over time and the effect of enrichment strategies.Alzheimers Res Ther. 2016 Feb 12;8:8. doi: 10.1186/s13195-016-0170-5.
• [2] Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
• [3] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [4] Novel compound heterozygous COG5 mutations in a Chinese male patient with severe clinical symptoms and type IIi congenital disorder of glycosylation: A case report.Exp Ther Med. 2019 Oct;18(4):2695-2700. doi: 10.3892/etm.2019.7834. Epub 2019 Jul 30.
• [5] CRISPR/Cas9-mediated gene knockout screens and target identification via whole-genome sequencing uncover host genes required for picornavirus infection. J Biol Chem. 2017 Jun 23;292(25):10664-10671. doi: 10.1074/jbc.M117.782425. Epub 2017 Apr 26.
• [6] A Mild Form of COG5 Defect Showing Early-Childhood-Onset Friedreich's-Ataxia-Like Phenotypes with Isolated Cerebellar Atrophy.J Korean Med Sci. 2017 Nov;32(11):1885-1890. doi: 10.3346/jkms.2017.32.11.1885.
• [7] Gene expression analysis reveals HBP1 as a key target for the osteoarthritis susceptibility locus that maps to chromosome 7q22.Ann Rheum Dis. 2012 Dec;71(12):2020-7. doi: 10.1136/annrheumdis-2012-201304. Epub 2012 May 14.
• [8] Fusion of HMGA2 to COG5 in uterine leiomyoma.Cancer Genet Cytogenet. 2010 Oct 1;202(1):11-6. doi: 10.1016/j.cancergencyto.2010.06.002.
• [9] Association analyses based on false discovery rate implicate new loci for coronary artery disease.Nat Genet. 2017 Sep;49(9):1385-1391. doi: 10.1038/ng.3913. Epub 2017 Jul 17.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] 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.
• [12] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [13] 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.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [16] 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.
• [17] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [18] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [19] 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.
• [20] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [21] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.