Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKQH4N4)

• DOT Name: Conserved oligomeric Golgi complex subunit 2 (COG2)
• Synonyms: COG complex subunit 2; Component of oligomeric Golgi complex 2; Low density lipoprotein receptor defect C-complementing protein
• Gene Name: COG2
• Related Disease:
  Hypobetalipoproteinemia
  Non-insulin dependent diabetes
  Cardiovascular disease
  Congenital disorder of glycosylation
  Congenital disorder of glycosylation, type IIq
  Constipation
  Familial hypercholesterolemia
  Hypercholesterolemia, familial, 1
  Gastric cancer
  Stomach cancer
  Coronary heart disease
  Rheumatoid arthritis
• UniProt ID: COG2_HUMAN
• Pfam ID: PF06148 ; PF12022
• Sequence:
  MEKSRMNLPKGPDTLCFDKDEFMKEDFDVDHFVSDCRKRVQLEELRDDLELYYKLLKTAM
  VELINKDYADFVNLSTNLVGMDKALNQLSVPLGQLREEVLSLRSSVSEGIRAVDERMSKQ
  EDIRKKKMCVLRLIQVIRSVEKIEKILNSQSSKETSALEASSPLLTGQILERIATEFNQL
  QFHAVQSKGMPLLDKVRPRIAGITAMLQQSLEGLLLEGLQTSDVDIIRHCLRTYATIDKT
  RDAEALVGQVLVKPYIDEVIIEQFVESHPNGLQVMYNKLLEFVPHHCRLLREVTGGAISS
  EKGNTVPGYDFLVNSVWPQIVQGLEEKLPSLFNPGNPDAFHEKYTISMDFVRRLERQCGS
  QASVKRLRAHPAYHSFNKKWNLPVYFQIRFREIAGSLEAALTDVLEDAPAESPYCLLASH
  RTWSSLRRCWSDEMFLPLLVHRLWRLTLQILARYSVFVNELSLRPISNESPKEIKKPLVT
  GSKEPSITQGNTEDQGSGPSETKPVVSISRTQLVYVVADLDKLQEQLPELLEIIKPKLEM
  IGFKNFSSISAALEDSQSSFSACVPSLSSKIIQDLSDSCFGFLKSALEVPRLYRRTNKEV
  PTTASSYVDSALKPLFQLQSGHKDKLKQAIIQQWLEGTLSESTHKYYETVSDVLNSVKKM
  EESLKRLKQARKTTPANPVGPSGGMSDDDKIRLQLALDVEYLGEQIQKLGLQASDIKSFS
  ALAELVAAAKDQATAEQP
• Function: Required for normal Golgi morphology and 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
Hypobetalipoproteinemia	DIS0TPI3	Definitive	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[2]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[3]
Congenital disorder of glycosylation	DIS400QP	Strong	Genetic Variation	[4]
Congenital disorder of glycosylation, type IIq	DISN2XAD	Strong	Autosomal recessive	[4]
Constipation	DISRQXWI	Strong	Biomarker	[5]
Familial hypercholesterolemia	DISC06IX	Strong	Biomarker	[6]
Hypercholesterolemia, familial, 1	DISU411W	Strong	Biomarker	[6]
Gastric cancer	DISXGOUK	moderate	Biomarker	[7]
Stomach cancer	DISKIJSX	moderate	Biomarker	[7]
Coronary heart disease	DIS5OIP1	Disputed	Biomarker	[8]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[9]

7 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 Conserved oligomeric Golgi complex subunit 2 (COG2).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Conserved oligomeric Golgi complex subunit 2 (COG2).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Conserved oligomeric Golgi complex subunit 2 (COG2).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Conserved oligomeric Golgi complex subunit 2 (COG2).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Conserved oligomeric Golgi complex subunit 2 (COG2).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Conserved oligomeric Golgi complex subunit 2 (COG2).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Conserved oligomeric Golgi complex subunit 2 (COG2).	[17]

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 2 (COG2).	[16]

References

• [1] PCSK9 dominant negative mutant results in increased LDL catabolic rate and familial hypobetalipoproteinemia.Arterioscler Thromb Vasc Biol. 2009 Dec;29(12):2191-7. doi: 10.1161/ATVBAHA.109.194191. Epub 2009 Sep 17.
• [2] Real-life achievement of lipid-lowering treatment targets in the DIAbetes and LifEstyle Cohort Twente: systemic assessment of pharmacological and nutritional factors.Nutr Diabetes. 2018 Apr 25;8(1):24. doi: 10.1038/s41387-018-0028-y.
• [3] Relationship between Long Interspersed Nuclear Element-1 DNA Methylation in Leukocytes and Dyslipidemia in the Japanese General Population.J Atheroscler Thromb. 2018 Dec 1;25(12):1231-1239. doi: 10.5551/jat.43570. Epub 2018 Apr 7.
• [4] Mutations in COG2 encoding a subunit of the conserved oligomeric golgi complex cause a congenital disorder of glycosylation. Clin Genet. 2015 May;87(5):455-60. doi: 10.1111/cge.12417. Epub 2014 May 24.
• [5] A randomized trial of the effects of flaxseed to manage constipation, weight, glycemia, and lipids in constipated patients with type 2 diabetes.Nutr Metab (Lond). 2018 May 9;15:36. doi: 10.1186/s12986-018-0273-z. eCollection 2018.
• [6] LDL apheresis in Japan.Transfus Apher Sci. 2017 Oct;56(5):677-681. doi: 10.1016/j.transci.2017.08.014. Epub 2017 Aug 31.
• [7] Prediction of three lipid derivatives for postoperative gastric cancer mortality: the Fujian prospective investigation of cancer (FIESTA) study.BMC Cancer. 2018 Aug 6;18(1):785. doi: 10.1186/s12885-018-4596-y.
• [8] Patients With High Genome-Wide Polygenic Risk Scores for Coronary Artery Disease May Receive Greater Clinical Benefit From Alirocumab Treatment in the ODYSSEY OUTCOMES Trial.Circulation. 2020 Feb 25;141(8):624-636. doi: 10.1161/CIRCULATIONAHA.119.044434. Epub 2019 Nov 11.
• [9] Association of serum lipids with autoantibodies and inflammatory markers in rheumatoid arthritis patients.Clin Chim Acta. 2018 Nov;486:282-290. doi: 10.1016/j.cca.2018.08.028. Epub 2018 Aug 18.
• [10] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [11] 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.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] 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.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] 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.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.