Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDEA7YO)

• DOT Name: Conserved oligomeric Golgi complex subunit 8 (COG8)
• Synonyms: COG complex subunit 8; Component of oligomeric Golgi complex 8
• Gene Name: COG8
• Related Disease:
  COG8-congenital disorder of glycosylation
  ALG2-congenital disorder of glycosylation
  Alveolar soft part sarcoma
  Arthrogryposis
  Colorectal carcinoma
  Congenital disorder of glycosylation
  Dandy-Walker syndrome
  Developmental and epileptic encephalopathy, 36
  Esophageal cancer
  Gastric cancer
  Hepatocellular carcinoma
  Lung cancer
• UniProt ID: COG8_HUMAN
• Pfam ID: PF04124
• Sequence:
  MATAATIPSVATATAAALGEVEDEGLLASLFRDRFPEAQWRERPDVGRYLRELSGSGLER
  LRREPERLAEERAQLLQQTRDLAFANYKTFIRGAECTERIHRLFGDVEASLGRLLDRLPS
  FQQSCRNFVKEAEEISSNRRMNSLTLNRHTEILEILEIPQLMDTCVRNSYYEEALELAAY
  VRRLERKYSSIPVIQGIVNEVRQSMQLMLSQLIQQLRTNIQLPACLRVIGYLRRMDVFTE
  AELRVKFLQARDAWLRSILTAIPNDDPYFHITKTIEASRVHLFDIITQYRAIFSDEDPLL
  PPAMGEHTVNESAIFHGWVLQKVSQFLQVLETDLYRGIGGHLDSLLGQCMYFGLSFSRVG
  ADFRGQLAPVFQRVAISTFQKAIQETVEKFQEEMNSYMLISAPAILGTSNMPAAVPATQP
  GTLQPPMVLLDFPPLACFLNNILVAFNDLRLCCPVALAQDVTGALEDALAKVTKIILAFH
  RAEEAAFSSGEQELFVQFCTVFLEDLVPYLNRCLQVLFPPAQIAQTLGIPPTQLSKYGNL
  GHVNIGAIQEPLAFILPKRETLFTLDDQALGPELTAPAPEPPAEEPRLEPAGPACPEGGR
  AETQAEPPSVGP
• 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

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
COG8-congenital disorder of glycosylation	DIS0L4MR	Definitive	Autosomal recessive	[1]
ALG2-congenital disorder of glycosylation	DISIVO8V	Strong	Biomarker	[2]
Alveolar soft part sarcoma	DISLKJKZ	Strong	Altered Expression	[3]
Arthrogryposis	DISC81CM	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Congenital disorder of glycosylation	DIS400QP	Strong	Biomarker	[4]
Dandy-Walker syndrome	DIS4HC6W	Strong	Biomarker	[4]
Developmental and epileptic encephalopathy, 36	DISG4MY5	Strong	Biomarker	[4]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[3]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Lung cancer	DISCM4YA	Strong	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Conserved oligomeric Golgi complex subunit 8 (COG8).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Conserved oligomeric Golgi complex subunit 8 (COG8).	[6]
Selenium	DM25CGV	Approved	Selenium increases the expression of Conserved oligomeric Golgi complex subunit 8 (COG8).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Conserved oligomeric Golgi complex subunit 8 (COG8).	[8]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Conserved oligomeric Golgi complex subunit 8 (COG8).	[10]

1 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 8 (COG8).	[9]

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] A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation. Hum Mol Genet. 2007 Apr 1;16(7):717-30. doi: 10.1093/hmg/ddl476. Epub 2007 Jan 12.
• [3] TMED6-COG8 is a novel molecular marker of TFE3 translocation renal cell carcinoma.Int J Clin Exp Pathol. 2015 Mar 1;8(3):2690-9. eCollection 2015.
• [4] The first case of antenatal presentation in COG8-congenital disorder of glycosylation with a novel splice site mutation and an extended phenotype.Am J Med Genet A. 2019 Mar;179(3):480-485. doi: 10.1002/ajmg.a.61030. Epub 2019 Jan 28.
• [5] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [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] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.