Details of Drug Off-Target (DOT)

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

• DOT Name: Conserved oligomeric Golgi complex subunit 6 (COG6)
• Synonyms: COG complex subunit 6; Component of oligomeric Golgi complex 6
• Gene Name: COG6
• Related Disease:
  Isolated congenital microcephaly
  Primary biliary cholangitis
  COG6-ongenital disorder of glycosylation
  Congenital disorder of glycosylation
  Developmental and epileptic encephalopathy, 36
  Non-immune hydrops fetalis
  Psoriasis
  Systemic lupus erythematosus
  Uterine fibroids
  Intellectual disability
  Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome
  Anhidrosis
  Rheumatoid arthritis
  Asthma
  Coronary heart disease
• UniProt ID: COG6_HUMAN
• Pfam ID: PF20653 ; PF06419
• Sequence:
  MAEGSGEVVAVSATGAANGLNNGAGGTSATTCNPLSRKLHKILETRLDNDKEMLEALKAL
  STFFVENSLRTRRNLRGDIERKSLAINEEFVSIFKEVKEELESISEDVQAMSNCCQDMTS
  RLQAAKEQTQDLIVKTTKLQSESQKLEIRAQVADAFLSKFQLTSDEMSLLRGTREGPITE
  DFFKALGRVKQIHNDVKVLLRTNQQTAGLEIMEQMALLQETAYERLYRWAQSECRTLTQE
  SCDVSPVLTQAMEALQDRPVLYKYTLDEFGTARRSTVVRGFIDALTRGGPGGTPRPIEMH
  SHDPLRYVGDMLAWLHQATASEKEHLEALLKHVTTQGVEENIQEVVGHITEGVCRPLKVR
  IEQVIVAEPGAVLLYKISNLLKFYHHTISGIVGNSATALLTTIEEMHLLSKKIFFNSLSL
  HASKLMDKVELPPPDLGPSSALNQTLMLLREVLASHDSSVVPLDARQADFVQVLSCVLDP
  LLQMCTVSASNLGTADMATFMVNSLYMMKTTLALFEFTDRRLEMLQFQIEAHLDTLINEQ
  ASYVLTRVGLSYIYNTVQQHKPEQGSLANMPNLDSVTLKAAMVQFDRYLSAPDNLLIPQL
  NFLLSATVKEQIVKQSTELVCRAYGEVYAAVMNPINEYKDPENILHRSPQQVQTLLS
• 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

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Isolated congenital microcephaly	DISUXHZ6	Definitive	Biomarker	[1]
Primary biliary cholangitis	DIS43E0O	Definitive	Genetic Variation	[2]
COG6-ongenital disorder of glycosylation	DISLXP0T	Strong	Autosomal recessive	[3]
Congenital disorder of glycosylation	DIS400QP	Strong	Genetic Variation	[4]
Developmental and epileptic encephalopathy, 36	DISG4MY5	Strong	Biomarker	[1]
Non-immune hydrops fetalis	DISPUY8C	Strong	Genetic Variation	[4]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[2]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[5]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[6]
Intellectual disability	DISMBNXP	moderate	Biomarker	[7]
Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome	DISX2SLW	Supportive	Autosomal recessive	[7]
Anhidrosis	DISYLSTC	Disputed	Genetic Variation	[8]
Rheumatoid arthritis	DISTSB4J	Disputed	Genetic Variation	[5]
Asthma	DISW9QNS	Limited	Genetic Variation	[9]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[10]

10 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 Conserved oligomeric Golgi complex subunit 6 (COG6).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Conserved oligomeric Golgi complex subunit 6 (COG6).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Conserved oligomeric Golgi complex subunit 6 (COG6).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Conserved oligomeric Golgi complex subunit 6 (COG6).	[14]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Conserved oligomeric Golgi complex subunit 6 (COG6).	[15]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Conserved oligomeric Golgi complex subunit 6 (COG6).	[16]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Conserved oligomeric Golgi complex subunit 6 (COG6).	[17]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Conserved oligomeric Golgi complex subunit 6 (COG6).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Conserved oligomeric Golgi complex subunit 6 (COG6).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Conserved oligomeric Golgi complex subunit 6 (COG6).	[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 decreases the methylation of Conserved oligomeric Golgi complex subunit 6 (COG6).	[19]

References

• [1] Compound heterozygous variants of the COG6 gene in a Chinese patient with deficiency of subunit 6 of the conserved oligomeric Golgi complex (COG6-CDG).Eur J Med Genet. 2019 Jan;62(1):44-46. doi: 10.1016/j.ejmg.2018.04.017. Epub 2018 Apr 28.
• [2] Allele-specific transcription factor binding to common and rare variants associated with disease and gene expression.Hum Genet. 2016 May;135(5):485-497. doi: 10.1007/s00439-016-1654-x. Epub 2016 Mar 18.
• [3] Fatal outcome due to deficiency of subunit 6 of the conserved oligomeric Golgi complex leading to a new type of congenital disorders of glycosylation. Hum Mol Genet. 2010 Sep 15;19(18):3623-33. doi: 10.1093/hmg/ddq278. Epub 2010 Jul 6.
• [4] Nonimmune hydrops fetalis and congenital disorders of glycosylation: A systematic literature review.J Inherit Metab Dis. 2020 Mar;43(2):223-233. doi: 10.1002/jimd.12162. Epub 2019 Nov 8.
• [5] A combined large-scale meta-analysis identifies COG6 as a novel shared risk locus for rheumatoid arthritis and systemic lupus erythematosus.Ann Rheum Dis. 2017 Jan;76(1):286-294. doi: 10.1136/annrheumdis-2016-209436. Epub 2016 May 18.
• [6] Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis.Nat Commun. 2019 Oct 24;10(1):4857. doi: 10.1038/s41467-019-12536-4.
• [7] A novel syndrome of hypohidrosis and intellectual disability is linked to COG6 deficiency. J Med Genet. 2013 Jul;50(7):431-6. doi: 10.1136/jmedgenet-2013-101527. Epub 2013 Apr 20.
• [8] Crisponi/CISS1 syndrome: A case series.Am J Med Genet A. 2016 May;170A(5):1236-41. doi: 10.1002/ajmg.a.37569. Epub 2016 Jan 24.
• [9] Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.Am J Hum Genet. 2019 Apr 4;104(4):665-684. doi: 10.1016/j.ajhg.2019.02.022. Epub 2019 Mar 28.
• [10] Polymorphism in miRNA-1 target site and circulating miRNA-1 phenotype are associated with the decreased risk and prognosis of coronary artery disease.Int J Clin Exp Pathol. 2014 Jul 15;7(8):5093-102. eCollection 2014.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] 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.
• [15] 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.
• [16] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [17] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [18] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [19] 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.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.