Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6U94UE)

DOT Name Conserved oligomeric Golgi complex subunit 4 (COG4)
Synonyms COG complex subunit 4; Component of oligomeric Golgi complex 4
Gene Name COG4
Related Disease
COG4-congenital disorder of glycosylation ( )
ALG2-congenital disorder of glycosylation ( )
Microcephalic osteodysplastic dysplasia, Saul-Wilson type ( )
Retinitis pigmentosa ( )
Sensorineural hearing loss disorder ( )
Cone dystrophy ( )
Precancerous condition ( )
Retinitis pigmentosa 3 ( )
UniProt ID
COG4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3HR0
Pfam ID
PF20662 ; PF08318 ; PF20663
Sequence
MADLDSPPKLSGVQQPSEGVGGGRCSEISAELIRSLTELQELEAVYERLCGEEKVVEREL
DALLEQQNTIESKMVTLHRMGPNLQLIEGDAKQLAGMITFTCNLAENVSSKVRQLDLAKN
RLYQAIQRADDILDLKFCMDGVQTALRSEDYEQAAAHTHRYLCLDKSVIELSRQGKEGSM
IDANLKLLQEAEQRLKAIVAEKFAIATKEGDLPQVERFFKIFPLLGLHEEGLRKFSEYLC
KQVASKAEENLLMVLGTDMSDRRAAVIFADTLTLLFEGIARIVETHQPIVETYYGPGRLY
TLIKYLQVECDRQVEKVVDKFIKQRDYHQQFRHVQNNLMRNSTTEKIEPRELDPILTEVT
LMNARSELYLRFLKKRISSDFEVGDSMASEEVKQEHQKCLDKLLNNCLLSCTMQELIGLY
VTMEEYFMRETVNKAVALDTYEKGQLTSSMVDDVFYIVKKCIGRALSSSSIDCLCAMINL
ATTELESDFRDVLCNKLRMGFPATTFQDIQRGVTSAVNIMHSSLQQGKFDTKGIESTDEA
KMSFLVTLNNVEVCSENISTLKKTLESDCTKLFSQGIGGEQAQAKFDSCLSDLAAVSNKF
RDLLQEGLTELNSTAIKPQVQPWINSFFSVSHNIEEEEFNDYEANDPWVQQFILNLEQQM
AEFKASLSPVIYDSLTGLMTSLVAVELEKVVLKSTFNRLGGLQFDKELRSLIAYLTTVTT
WTIRDKFARLSQMATILNLERVTEILDYWGPNSGPLTWRLTPAEVRQVLALRIDFRSEDI
KRLRL
Function Required for normal Golgi function. Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1.
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

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
COG4-congenital disorder of glycosylation DIS5TU0H Definitive Autosomal recessive [1]
ALG2-congenital disorder of glycosylation DISIVO8V Strong Genetic Variation [2]
Microcephalic osteodysplastic dysplasia, Saul-Wilson type DISI3TP6 Strong Autosomal dominant [3]
Retinitis pigmentosa DISCGPY8 Strong Genetic Variation [4]
Sensorineural hearing loss disorder DISJV45Z moderate Genetic Variation [5]
Cone dystrophy DIS7SAZZ Limited Genetic Variation [6]
Precancerous condition DISV06FL Limited Biomarker [7]
Retinitis pigmentosa 3 DIS4VBK1 Limited Biomarker [8]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Conserved oligomeric Golgi complex subunit 4 (COG4). [9]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Conserved oligomeric Golgi complex subunit 4 (COG4). [10]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Conserved oligomeric Golgi complex subunit 4 (COG4). [11]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Conserved oligomeric Golgi complex subunit 4 (COG4). [12]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Conserved oligomeric Golgi complex subunit 4 (COG4). [13]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Conserved oligomeric Golgi complex subunit 4 (COG4). [14]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Conserved oligomeric Golgi complex subunit 4 (COG4). [15]
ACYLINE DM9GRTK Phase 2 ACYLINE increases the expression of Conserved oligomeric Golgi complex subunit 4 (COG4). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Conserved oligomeric Golgi complex subunit 4 (COG4). [19]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Conserved oligomeric Golgi complex subunit 4 (COG4). [20]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Conserved oligomeric Golgi complex subunit 4 (COG4). [21]
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⏷ Show the Full List of 11 Drug(s)
1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
DNCB DMDTVYC Phase 2 DNCB affects the binding of Conserved oligomeric Golgi complex subunit 4 (COG4). [16]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of Conserved oligomeric Golgi complex subunit 4 (COG4). [18]
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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 Golgi function and dysfunction in the first COG4-deficient CDG type II patient. Hum Mol Genet. 2009 Sep 1;18(17):3244-56. doi: 10.1093/hmg/ddp262. Epub 2009 Jun 3.
3 A Recurrent De Novo Heterozygous COG4 Substitution Leads to Saul-Wilson Syndrome, Disrupted Vesicular Trafficking, and Altered Proteoglycan Glycosylation. Am J Hum Genet. 2018 Oct 4;103(4):553-567. doi: 10.1016/j.ajhg.2018.09.003.
4 A new genetic locus for X linked progressive cone-rod dystrophy.J Med Genet. 2003 Jun;40(6):418-23. doi: 10.1136/jmg.40.6.418.
5 Cog4 is required for protrusion and extension of the epithelium in the developing semicircular canals.Mech Dev. 2019 Feb;155:1-7. doi: 10.1016/j.mod.2018.09.003. Epub 2018 Oct 1.
6 Mutations in the RPGR gene cause X-linked cone dystrophy.Hum Mol Genet. 2002 Mar 1;11(5):605-11. doi: 10.1093/hmg/11.5.605.
7 Hepatocellular carcinoma-associated protein markers investigated by MALDI-TOF MS.Mol Med Rep. 2010 Jul-Aug;3(4):589-96. doi: 10.3892/mmr_00000302.
8 Remapping of the RP15 locus for X-linked cone-rod degeneration to Xp11.4-p21.1, and identification of a de novo insertion in the RPGR exon ORF15.Am J Hum Genet. 2000 Oct;67(4):1000-3. doi: 10.1086/303091. Epub 2000 Sep 1.
9 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
10 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
11 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.
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 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
15 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
16 Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
17 Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 2007 May 15;67(10):5033-41.
18 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.
19 Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
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.