Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYHIYN2)

• DOT Name: Golgi SNAP receptor complex member 2 (GOSR2)
• Synonyms: 27 kDa Golgi SNARE protein; Membrin
• Gene Name: GOSR2
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Atrial fibrillation
  Branchiootic syndrome
  Bronchiolitis obliterans syndrome
  Cardiovascular disease
  Cerebellar ataxia
  Essential hypertension
  Isolated cleft lip
  Movement disorder
  Myocardial infarction
  Progressive myoclonic epilepsy type 6
  Trichohepatoenteric syndrome
  Unverricht-Lundborg syndrome
  Congenital muscular dystrophy
  Coronary heart disease
  Familial atrial fibrillation
  Muscular dystrophy
  High blood pressure
  Muscular dystrophy, congenital, with or without seizures
  Progressive myoclonus epilepsy
• UniProt ID: GOSR2_HUMAN
• PDB ID: 3EG9
• Pfam ID: PF12352
• Sequence:
  MDPLFQQTHKQVHEIQSCMGRLETADKQSVHIVENEIQASIDQIFSRLERLEILSSKEPP
  NKRQNARLRVDQLKYDVQHLQTALRNFQHRRHAREQQERQREELLSRTFTTNDSDTTIPM
  DESLQFNSSLQKVHNGMDDLILDGHNILDGLRTQRLTLKGTQKKILDIANMLGLSNTVMR
  LIEKRAFQDKYFMIGGMLLTCVVMFLVVQYLT
• Function: Involved in transport of proteins from the cis/medial-Golgi to the trans-Golgi network.
• KEGG Pathway: S.RE interactions in vesicular transport (hsa04130)
• Reactome Pathway:
  XBP1(S) activates chaperone genes (R-HSA-381038)
  Cargo concentration in the ER (R-HSA-5694530)
  COPI-mediated anterograde transport (R-HSA-6807878)
  Intra-Golgi traffic (R-HSA-6811438)
  COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[1]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[1]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[2]
Branchiootic syndrome	DIS3X164	Strong	Biomarker	[3]
Bronchiolitis obliterans syndrome	DISCK9IV	Strong	Genetic Variation	[4]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[5]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[6]
Essential hypertension	DIS7WI98	Strong	Biomarker	[7]
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[8]
Movement disorder	DISOJJ2D	Strong	Genetic Variation	[9]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[10]
Progressive myoclonic epilepsy type 6	DIS06G6V	Strong	Autosomal recessive	[11]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[12]
Unverricht-Lundborg syndrome	DISG4WLX	Strong	Biomarker	[6]
Congenital muscular dystrophy	DISKY7OY	moderate	Genetic Variation	[13]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[14]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[2]
Muscular dystrophy	DISJD6P7	moderate	Genetic Variation	[13]
High blood pressure	DISY2OHH	Limited	Biomarker	[7]
Muscular dystrophy, congenital, with or without seizures	DISBTHTO	Limited	Unknown	[15]
Progressive myoclonus epilepsy	DISAMCNS	Limited	Genetic Variation	[6]

14 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 Golgi SNAP receptor complex member 2 (GOSR2).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Golgi SNAP receptor complex member 2 (GOSR2).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Golgi SNAP receptor complex member 2 (GOSR2).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Golgi SNAP receptor complex member 2 (GOSR2).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Golgi SNAP receptor complex member 2 (GOSR2).	[20]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Golgi SNAP receptor complex member 2 (GOSR2).	[21]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Golgi SNAP receptor complex member 2 (GOSR2).	[22]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Golgi SNAP receptor complex member 2 (GOSR2).	[23]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Golgi SNAP receptor complex member 2 (GOSR2).	[24]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Golgi SNAP receptor complex member 2 (GOSR2).	[25]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Golgi SNAP receptor complex member 2 (GOSR2).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Golgi SNAP receptor complex member 2 (GOSR2).	[27]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Golgi SNAP receptor complex member 2 (GOSR2).	[28]
CHLORANIL	DMCHGF1	Investigative	CHLORANIL increases the expression of Golgi SNAP receptor complex member 2 (GOSR2).	[29]

References

• [1] GOSR2 Lys67Arg is associated with hypertension in whites.Am J Hypertens. 2009 Feb;22(2):163-8. doi: 10.1038/ajh.2008.336. Epub 2008 Dec 4.
• [2] Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
• [3] EYA1-related disorders: two clinical cases and a literature review.Int J Pediatr Otorhinolaryngol. 2014 Aug;78(8):1201-10. doi: 10.1016/j.ijporl.2014.03.032. Epub 2014 Apr 12.
• [4] (1)H NMR To Evaluate the Metabolome of Bronchoalveolar Lavage Fluid (BALf) in Bronchiolitis Obliterans Syndrome (BOS): Toward the Development of a New Approach for Biomarker Identification.J Proteome Res. 2017 Apr 7;16(4):1669-1682. doi: 10.1021/acs.jproteome.6b01038. Epub 2017 Mar 14.
• [5] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [6] Mechanisms of Neurological Dysfunction in GOSR2 Progressive Myoclonus Epilepsy, a Golgi SNAREopathy.Neuroscience. 2019 Nov 10;420:41-49. doi: 10.1016/j.neuroscience.2019.03.057. Epub 2019 Apr 4.
• [7] A haplotype of the GOSR2 gene is associated with essential hypertension in Japanese men.Clin Biochem. 2013 Jun;46(9):760-5. doi: 10.1016/j.clinbiochem.2012.12.021. Epub 2013 Jan 11.
• [8] Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity.Nat Commun. 2017 Feb 24;8:14364. doi: 10.1038/ncomms14364.
• [9] Ramsay Hunt syndrome: clinical characterization of progressive myoclonus ataxia caused by GOSR2 mutation.Mov Disord. 2014 Jan;29(1):139-43. doi: 10.1002/mds.25704. Epub 2013 Oct 30.
• [10] A haplotype of the GOSR2 gene is associated with myocardial infarction in Japanese men.Genet Test Mol Biomarkers. 2013 Jun;17(6):481-8. doi: 10.1089/gtmb.2012.0379. Epub 2013 May 15.
• [11] A mutation in the Golgi Qb-SNARE gene GOSR2 causes progressive myoclonus epilepsy with early ataxia. Am J Hum Genet. 2011 May 13;88(5):657-63. doi: 10.1016/j.ajhg.2011.04.011. Epub 2011 May 5.
• [12] 'North Sea' progressive myoclonus epilepsy: phenotype of subjects with GOSR2 mutation.Brain. 2013 Apr;136(Pt 4):1146-54. doi: 10.1093/brain/awt021. Epub 2013 Feb 28.
• [13] TRAPPC11 and GOSR2 mutations associate with hypoglycosylation of -dystroglycan and muscular dystrophy.Skelet Muscle. 2018 May 31;8(1):17. doi: 10.1186/s13395-018-0163-0.
• [14] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [15] Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA. 2014 Nov 12;312(18):1880-7. doi: 10.1001/jama.2014.14604.
• [16] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [17] 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.
• [18] 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.
• [19] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [20] 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.
• [21] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [22] 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.
• [23] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [24] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [25] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [26] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [27] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [28] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [29] Redox-active quinones induces genome-wide DNA methylation changes by an iron-mediated and Tet-dependent mechanism. Nucleic Acids Res. 2014 Feb;42(3):1593-605. doi: 10.1093/nar/gkt1090. Epub 2013 Nov 8.