Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQBDO45)

• DOT Name: Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1)
• Synonyms: EC 2.6.1.16; D-fructose-6-phosphate amidotransferase 1; Glutamine:fructose-6-phosphate amidotransferase 1; GFAT 1; GFAT1; Hexosephosphate aminotransferase 1
• Gene Name: GFPT1
• Related Disease:
  Congenital myasthenic syndrome 12
  Hyperglycemia
  Non-insulin dependent diabetes
  Tubular aggregate myopathy
  Advanced cancer
  Brain neoplasm
  Diabetic kidney disease
  Glioblastoma multiforme
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Neuromuscular disease
  Neuromuscular junction disease
  Obesity
  Pancreatic cancer
  Triple negative breast cancer
  Gastric cancer
  Metastatic malignant neoplasm
  Myopathy
  Neoplasm
  Nephropathy
  Postsynaptic congenital myasthenic syndrome
  Stomach cancer
  Type-1/2 diabetes
  Obsolete congenital myasthenic syndromes with glycosylation defect
  Breast cancer
  Breast carcinoma
  Congenital myasthenic syndrome
  Hyperinsulinemia
  Hyperlipidemia
  Hyperlipoproteinemia
  Nasopharyngeal carcinoma
• UniProt ID: GFPT1_HUMAN
• PDB ID: 2V4M; 2ZJ3; 2ZJ4; 6R4E; 6R4F; 6R4G; 6R4H; 6R4I; 6R4J; 6SVM; 6SVO; 6SVP; 6SVQ; 6ZMJ; 6ZMK; 7NDL
• EC Number: 2.6.1.16
• Pfam ID: PF13522 ; PF01380
• Sequence:
  MCGIFAYLNYHVPRTRREILETLIKGLQRLEYRGYDSAGVGFDGGNDKDWEANACKIQLI
  KKKGKVKALDEEVHKQQDMDLDIEFDVHLGIAHTRWATHGEPSPVNSHPQRSDKNNEFIV
  IHNGIITNYKDLKKFLESKGYDFESETDTETIAKLVKYMYDNRESQDTSFTTLVERVIQQ
  LEGAFALVFKSVHFPGQAVGTRRGSPLLIGVRSEHKLSTDHIPILYRTARTQIGSKFTRW
  GSQGERGKDKKGSCNLSRVDSTTCLFPVEEKAVEYYFASDASAVIEHTNRVIFLEDDDVA
  AVVDGRLSIHRIKRTAGDHPGRAVQTLQMELQQIMKGNFSSFMQKEIFEQPESVVNTMRG
  RVNFDDYTVNLGGLKDHIKEIQRCRRLILIACGTSYHAGVATRQVLEELTELPVMVELAS
  DFLDRNTPVFRDDVCFFLSQSGETADTLMGLRYCKERGALTVGITNTVGSSISRETDCGV
  HINAGPEIGVASTKAYTSQFVSLVMFALMMCDDRISMQERRKEIMLGLKRLPDLIKEVLS
  MDDEIQKLATELYHQKSVLIMGRGYHYATCLEGALKIKEITYMHSEGILAGELKHGPLAL
  VDKLMPVIMIIMRDHTYAKCQNALQQVVARQGRPVVICDKEDTETIKNTKRTIKVPHSVD
  CLQGILSVIPLQLLAFHLAVLRGYDVDFPRNLAKSVTVE
• Function: Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins. Regulates the circadian expression of clock genes BMAL1 and CRY1. Has a role in fine tuning the metabolic fluctuations of cytosolic UDP-GlcNAc and its effects on hyaluronan synthesis that occur during tissue remodeling.
• Tissue Specificity: Isoform 1 is predominantly expressed in skeletal muscle. Not expressed in brain. Seems to be selectively expressed in striated muscle.
• KEGG Pathway:
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
  Biosynthesis of nucleotide sugars (hsa01250)
  Insulin resistance (hsa04931)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Defective GFPT1 causes CMSTA1 (R-HSA-4085023)
  Synthesis of UDP-N-acetyl-glucosamine (R-HSA-446210)
  XBP1(S) activates chaperone genes (R-HSA-381038)
• BioCyc Pathway: MetaCyc:HS09974-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital myasthenic syndrome 12	DISFU9PF	Definitive	Autosomal recessive	[1]
Hyperglycemia	DIS0BZB5	Definitive	Genetic Variation	[2]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Altered Expression	[3]
Tubular aggregate myopathy	DISC11WH	Definitive	Genetic Variation	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[5]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[6]
Diabetic kidney disease	DISJMWEY	Strong	Altered Expression	[7]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[8]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Neuromuscular disease	DISQTIJZ	Strong	Genetic Variation	[11]
Neuromuscular junction disease	DIS8VKGV	Strong	Genetic Variation	[12]
Obesity	DIS47Y1K	Strong	Biomarker	[13]
Pancreatic cancer	DISJC981	Strong	Biomarker	[14]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[15]
Gastric cancer	DISXGOUK	moderate	Biomarker	[16]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[16]
Myopathy	DISOWG27	moderate	Genetic Variation	[17]
Neoplasm	DISZKGEW	moderate	Altered Expression	[10]
Nephropathy	DISXWP4P	moderate	Altered Expression	[7]
Postsynaptic congenital myasthenic syndrome	DIS92VN2	moderate	Biomarker	[18]
Stomach cancer	DISKIJSX	moderate	Biomarker	[16]
Type-1/2 diabetes	DISIUHAP	moderate	Altered Expression	[7]
Obsolete congenital myasthenic syndromes with glycosylation defect	DISIGACA	Supportive	Autosomal recessive	[19]
Breast cancer	DIS7DPX1	Limited	Biomarker	[20]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[20]
Congenital myasthenic syndrome	DISJLG2T	Limited	Biomarker	[21]
Hyperinsulinemia	DISIDWT6	Limited	Biomarker	[22]
Hyperlipidemia	DIS61J3S	Limited	Biomarker	[22]
Hyperlipoproteinemia	DISVBLBO	Limited	Biomarker	[22]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[23]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1) decreases the response to substance of Paclitaxel.	[42]
Gabapentin	DM6T924	Approved	Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1) increases the Diabetic complications renal ADR of Gabapentin.	[43]
L-glutamine	DM69G8X	Approved	Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1) increases the Cytogenetic investigations ADR of L-glutamine.	[43]

18 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 Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[24]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[26]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[27]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[28]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[29]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[31]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[32]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[33]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[34]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[35]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[36]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[37]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[38]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[40]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[41]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1).	[30]

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