Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK2N05B)

• DOT Name: 1,4-alpha-glucan-branching enzyme (GBE1)
• Synonyms: EC 2.4.1.18; Brancher enzyme; Glycogen-branching enzyme
• Gene Name: GBE1
• Related Disease:
  Glycogen storage disease due to glycogen branching enzyme deficiency
  Type-1/2 diabetes
  Advanced cancer
  Arthrogryposis
  B-cell neoplasm
  Carnitine palmitoyltransferase II deficiency
  Chronic inflammatory demyelinating polyneuropathy
  Chylomicron retention disease
  Congenital myopathy
  Cytochrome-c oxidase deficiency disease
  Disorder of glycogen metabolism
  Esophageal squamous cell carcinoma
  Fetal akinesia deformation sequence 1
  Gerstmann-Straussler-Scheinker syndrome
  Glycogen storage disease III
  Glycogen storage disease type II
  Leukodystrophy
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Metabolic disorder
  Mitochondrial disease
  Mitochondrial trifunctional protein deficiency
  Multiple sclerosis
  Myopathy
  Neoplasm
  Porphyria
  Stroke
  Acute myelogenous leukaemia
  Adult polyglucosan body disease
  Cardiomyopathy
  Ovarian neoplasm
  Autosomal recessive multiple pterygium syndrome
  Dilated cardiomyopathy 1A
  Lethal multiple pterygium syndrome
  Melanoma
• UniProt ID: GLGB_HUMAN
• PDB ID: 4BZY; 5CLT; 5CLW
• EC Number: 2.4.1.18
• Pfam ID: PF00128 ; PF02806 ; PF02922
• Sequence:
  MAAPMTPAARPEDYEAALNAALADVPELARLLEIDPYLKPYAVDFQRRYKQFSQILKNIG
  ENEGGIDKFSRGYESFGVHRCADGGLYCKEWAPGAEGVFLTGDFNGWNPFSYPYKKLDYG
  KWELYIPPKQNKSVLVPHGSKLKVVITSKSGEILYRISPWAKYVVREGDNVNYDWIHWDP
  EHSYEFKHSRPKKPRSLRIYESHVGISSHEGKVASYKHFTCNVLPRIKGLGYNCIQLMAI
  MEHAYYASFGYQITSFFAASSRYGTPEELQELVDTAHSMGIIVLLDVVHSHASKNSADGL
  NMFDGTDSCYFHSGPRGTHDLWDSRLFAYSSWEILRFLLSNIRWWLEEYRFDGFRFDGVT
  SMLYHHHGVGQGFSGDYSEYFGLQVDEDALTYLMLANHLVHTLCPDSITIAEDVSGMPAL
  CSPISQGGGGFDYRLAMAIPDKWIQLLKEFKDEDWNMGDIVYTLTNRRYLEKCIAYAESH
  DQALVGDKSLAFWLMDAEMYTNMSVLTPFTPVIDRGIQLHKMIRLITHGLGGEGYLNFMG
  NEFGHPEWLDFPRKGNNESYHYARRQFHLTDDDLLRYKFLNNFDRDMNRLEERYGWLAAP
  QAYVSEKHEGNKIIAFERAGLLFIFNFHPSKSYTDYRVGTALPGKFKIVLDSDAAEYGGH
  QRLDHSTDFFSEAFEHNGRPYSLLVYIPSRVALILQNVDLPN
• Function: Required for normal glycogen accumulation. The alpha 1-6 branches of glycogen play an important role in increasing the solubility of the molecule (Probable).
• KEGG Pathway:
  Starch and sucrose metabolism (hsa00500)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Glycogen storage disease type IV (GBE1) (R-HSA-3878781)
  Glycogen synthesis (R-HSA-3322077)
• BioCyc Pathway: MetaCyc:HS03772-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glycogen storage disease due to glycogen branching enzyme deficiency	DIS3H8HJ	Definitive	Autosomal recessive	[1]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Arthrogryposis	DISC81CM	Strong	Genetic Variation	[4]
B-cell neoplasm	DISVY326	Strong	Genetic Variation	[5]
Carnitine palmitoyltransferase II deficiency	DIS3GFD9	Strong	Biomarker	[6]
Chronic inflammatory demyelinating polyneuropathy	DISNGBLD	Strong	Genetic Variation	[5]
Chylomicron retention disease	DISOUTV5	Strong	Biomarker	[7]
Congenital myopathy	DISLSK9G	Strong	Biomarker	[8]
Cytochrome-c oxidase deficiency disease	DISK7N3G	Strong	Biomarker	[6]
Disorder of glycogen metabolism	DISYGNOB	Strong	Biomarker	[9]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[10]
Fetal akinesia deformation sequence 1	DISKDI9L	Strong	Biomarker	[11]
Gerstmann-Straussler-Scheinker syndrome	DISIO6KC	Strong	Biomarker	[12]
Glycogen storage disease III	DISTXQ1P	Strong	Genetic Variation	[13]
Glycogen storage disease type II	DISXZPBC	Strong	Biomarker	[13]
Leukodystrophy	DISVY1TT	Strong	Biomarker	[14]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	Strong	Biomarker	[3]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[15]
Mitochondrial disease	DISKAHA3	Strong	Biomarker	[6]
Mitochondrial trifunctional protein deficiency	DIS2MYYR	Strong	Biomarker	[6]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[16]
Myopathy	DISOWG27	Strong	Genetic Variation	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Porphyria	DIS9YL4C	Strong	Genetic Variation	[18]
Stroke	DISX6UHX	Strong	Biomarker	[14]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[19]
Adult polyglucosan body disease	DISDQNH7	Moderate	Autosomal recessive	[20]
Cardiomyopathy	DISUPZRG	moderate	Genetic Variation	[21]
Ovarian neoplasm	DISEAFTY	moderate	Biomarker	[22]
Autosomal recessive multiple pterygium syndrome	DISVK1D4	Limited	Genetic Variation	[23]
Dilated cardiomyopathy 1A	DIS0RK9Z	Limited	Biomarker	[9]
Lethal multiple pterygium syndrome	DIS668BA	Limited	Genetic Variation	[23]
Melanoma	DIS1RRCY	Limited	Biomarker	[24]

23 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 1,4-alpha-glucan-branching enzyme (GBE1).	[25]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[26]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[27]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[28]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[29]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[30]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[31]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[32]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[33]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[34]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[35]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[36]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[37]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[38]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[38]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[38]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[34]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[34]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[40]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[42]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[43]
Choline	DM5D9YK	Investigative	Choline affects the expression of 1,4-alpha-glucan-branching enzyme (GBE1).	[44]

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 1,4-alpha-glucan-branching enzyme (GBE1).	[41]

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