Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9PU6I2)

• DOT Name: Glycogenin-1 (GYG1)
• Synonyms: GN-1; GN1; EC 2.4.1.186
• Gene Name: GYG1
• Related Disease:
  Polyglucosan body myopathy type 2
  Arrhythmia
  Cardiomyopathy
  Gerstmann-Straussler-Scheinker syndrome
  Glycogen storage disease XV
  Lafora disease
  Metabolic disorder
  Myocardial ischemia
  Myopathy
  Skeletal muscle disorder
  Disorder of glycogen metabolism
  Glycogen storage disease type II
  Non-insulin dependent diabetes
• UniProt ID: GLYG_HUMAN
• PDB ID: 3Q4S; 3QVB; 3RMV; 3RMW; 3T7M; 3T7N; 3T7O; 3U2T; 3U2U; 3U2V; 3U2W; 3U2X; 6EQJ; 6EQL; 7OVX; 7Q0B; 7Q0S; 7Q12; 7Q13; 7ZBN; 8CVX; 8CVY; 8CVZ
• EC Number: 2.4.1.186
• Pfam ID: PF01501
• Sequence:
  MTDQAFVTLTTNDAYAKGALVLGSSLKQHRTTRRLVVLATPQVSDSMRKVLETVFDEVIM
  VDVLDSGDSAHLTLMKRPELGVTLTKLHCWSLTQYSKCVFMDADTLVLANIDDLFDREEL
  SAAPDPGWPDCFNSGVFVYQPSVETYNQLLHLASEQGSFDGGDQGILNTFFSSWATTDIR
  KHLPFIYNLSSISIYSYLPAFKVFGASAKVVHFLGRVKPWNYTYDPKTKSVKSEAHDPNM
  THPEFLILWWNIFTTNVLPLLQQFGLVKDTCSYVNVLSDLVYTLAFSCGFCRKEDVSGAI
  SHLSLGEIPAMAQPFVSSEERKERWEQGQADYMGADSFDNIKRKLDTYLQ
• Function: Glycogenin participates in the glycogen biosynthetic process along with glycogen synthase and glycogen branching enzyme. It self-glucosylates, via an inter-subunit mechanism, to form an oligosaccharide primer that serves as substrate for glycogen synthase.
• Tissue Specificity: Highly expressed in skeletal muscle and heart, with lower levels in brain, lung, kidney and pancreas.
• KEGG Pathway:
  Starch and sucrose metabolism (hsa00500)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Myoclonic epilepsy of Lafora (R-HSA-3785653)
  Glycogen storage disease type XV (GYG1) (R-HSA-3814836)
  Glycogen storage disease type 0 (muscle GYS1) (R-HSA-3828062)
  Glycogen storage disease type II (GAA) (R-HSA-5357609)
  Neutrophil degranulation (R-HSA-6798695)
  Glycogen breakdown (glycogenolysis) (R-HSA-70221)
  Glycogen synthesis (R-HSA-3322077)
• BioCyc Pathway: MetaCyc:HS08931-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Polyglucosan body myopathy type 2	DIS2WYCO	Definitive	Autosomal recessive	[1]
Arrhythmia	DISFF2NI	Strong	Biomarker	[2]
Cardiomyopathy	DISUPZRG	Strong	Altered Expression	[3]
Gerstmann-Straussler-Scheinker syndrome	DISIO6KC	Strong	Genetic Variation	[4]
Glycogen storage disease XV	DISEFBJL	Strong	Autosomal recessive	[5]
Lafora disease	DIS83JHH	Strong	Biomarker	[6]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[7]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[8]
Myopathy	DISOWG27	Strong	Biomarker	[9]
Skeletal muscle disorder	DISR9DGU	Strong	Genetic Variation	[9]
Disorder of glycogen metabolism	DISYGNOB	Limited	Biomarker	[10]
Glycogen storage disease type II	DISXZPBC	Limited	Altered Expression	[11]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[12]

11 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 Glycogenin-1 (GYG1).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Glycogenin-1 (GYG1).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Glycogenin-1 (GYG1).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glycogenin-1 (GYG1).	[16]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Glycogenin-1 (GYG1).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glycogenin-1 (GYG1).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glycogenin-1 (GYG1).	[19]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Glycogenin-1 (GYG1).	[20]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Glycogenin-1 (GYG1).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glycogenin-1 (GYG1).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Glycogenin-1 (GYG1).	[25]

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 Glycogenin-1 (GYG1).	[22]

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 Glycogenin-1 (GYG1).	[23]

References

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• [10] Cardiomyopathy as presenting sign of glycogenin-1 deficiency-report of three cases and review of the literature.J Inherit Metab Dis. 2017 Jan;40(1):139-149. doi: 10.1007/s10545-016-9978-1. Epub 2016 Oct 7.
• [11] A newly identified c.1824_1828dupATACG mutation in exon 13 of the GAA gene in infantile-onset glycogen storage disease type II (Pompe disease).Mol Biol Rep. 2014 Sep;41(9):6211-4. doi: 10.1007/s11033-014-3500-3. Epub 2014 Jun 30.
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