Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCV4JC1)

• DOT Name: Conserved oligomeric Golgi complex subunit 7 (COG7)
• Synonyms: COG complex subunit 7; Component of oligomeric Golgi complex 7
• Gene Name: COG7
• Related Disease:
  COG7-congenital disorder of glycosylation
  Congenital disorder of glycosylation
  Isolated congenital microcephaly
• UniProt ID: COG7_HUMAN
• Pfam ID: PF10191
• Sequence:
  MDFSKFLADDFDVKEWINAAFRAGSKEAASGKADGHAATLVMKLQLFIQEVNHAVEETSH
  QALQNMPKVLRDVEALKQEASFLKEQMILVKEDIKKFEQDTSQSMQVLVEIDQVKSRMQL
  AAESLQEADKWSTLSADIEETFKTQDIAVISAKLTGMQNSLMMLVDTPDYSEKCVHLEAL
  KNRLEALASPQIVAAFTSQAVDQSKVFVKVFTEIDRMPQLLAYYYKCHKVQLLAAWQELC
  QSDLSLDRQLTGLYDALLGAWHTQIQWATQVFQKPHEVVMVLLIQTLGALMPSLPSCLSN
  GVERAGPEQELTRLLEFYDATAHFAKGLEMALLPHLHEHNLVKVTELVDAVYDPYKPYQL
  KYGDMEESNLLIQMSAVPLEHGEVIDCVQELSHSVNKLFGLASAAVDRCVRFTNGLGTCG
  LLSALKSLFAKYVSDFTSTLQSIRKKCKLDHIPPNSLFQEDWTAFQNSIRIIATCGELLR
  HCGDFEQQLANRILSTAGKYLSDSCSPRSLAGFQESILTDKKNSAKNPWQEYNYLQKDNP
  AEYASLMEILYTLKEKGSSNHNLLAAPRAALTRLNQQAHQLAFDSVFLRIKQQLLLISKM
  DSWNTAGIGETLTDELPAFSLTPLEYISNIGQYIMSLPLNLEPFVTQEDSALELALHAGK
  LPFPPEQGDELPELDNMADNWLGSIARATMQTYCDAILQIPELSPHSAKQLATDIDYLIN
  VMDALGLQPSRTLQHIVTLLKTRPEDYRQVSKGLPRRLATTVATMRSVNY
• 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

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
COG7-congenital disorder of glycosylation	DIS1TIYU	Definitive	Autosomal recessive	[1]
Congenital disorder of glycosylation	DIS400QP	Strong	Biomarker	[2]
Isolated congenital microcephaly	DISUXHZ6	moderate	Genetic Variation	[3]

7 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 7 (COG7).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Conserved oligomeric Golgi complex subunit 7 (COG7).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Conserved oligomeric Golgi complex subunit 7 (COG7).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Conserved oligomeric Golgi complex subunit 7 (COG7).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Conserved oligomeric Golgi complex subunit 7 (COG7).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Conserved oligomeric Golgi complex subunit 7 (COG7).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Conserved oligomeric Golgi complex subunit 7 (COG7).	[13]

3 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 affects the methylation of Conserved oligomeric Golgi complex subunit 7 (COG7).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Conserved oligomeric Golgi complex subunit 7 (COG7).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Conserved oligomeric Golgi complex subunit 7 (COG7).	[12]

References

• [1] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [2] COG7 deficiency in Drosophila generates multifaceted developmental, behavioral and protein glycosylation phenotypes.J Cell Sci. 2017 Nov 1;130(21):3637-3649. doi: 10.1242/jcs.209049. Epub 2017 Sep 7.
• [3] A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.Eur J Hum Genet. 2007 Jun;15(6):638-45. doi: 10.1038/sj.ejhg.5201813. Epub 2007 Mar 14.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] 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.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] 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.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.