Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH7BWNL)

DOT Name Glucose-6-phosphatase 3 (G6PC3)
Synonyms G-6-Pase 3; G6Pase 3; EC 3.1.3.9; Glucose-6-phosphatase beta; G6Pase-beta; Ubiquitous glucose-6-phosphatase catalytic subunit-related protein
Gene Name G6PC3
Related Disease
Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency ( )
UniProt ID
G6PC3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.1.3.9
Pfam ID
PF01569
Sequence
MESTLGAGIVIAEALQNQLAWLENVWLWITFLGDPKILFLFYFPAAYYASRRVGIAVLWI
SLITEWLNLIFKWFLFGDRPFWWVHESGYYSQAPAQVHQFPSSCETGPGSPSGHCMITGA
ALWPIMTALSSQVATRARSRWVRVMPSLAYCTFLLAVGLSRIFILAHFPHQVLAGLITGA
VLGWLMTPRVPMERELSFYGLTALALMLGTSLIYWTLFTLGLDLSWSISLAFKWCERPEW
IHVDSRPFASLSRDSGAALGLGIALHSPCYAQVRRAQLGNGQKIACLVLAMGLLGPLDWL
GHPPQISLFYIFNFLKYTLWPCLVLALVPWAVHMFSAQEAPPIHSS
Function
Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. May form with the glucose-6-phosphate transporter (SLC37A4/G6PT) a ubiquitously expressed complex responsible for glucose production through glycogenolysis and gluconeogenesis. Probably required for normal neutrophil function.
Tissue Specificity
Ubiquitously expressed. Highly expressed in skeletal muscle, at intermediate levels in heart, brain, placenta, kidney, colon, thymus, spleen and pancreas. Also detected in testis, prostate, ovary, liver, lung, small intestine and peripheral blood lymphocytes.
KEGG Pathway
Glycolysis / Gluconeogenesis (hsa00010 )
Galactose metabolism (hsa00052 )
Starch and sucrose metabolism (hsa00500 )
Metabolic pathways (hsa01100 )
FoxO sig.ling pathway (hsa04068 )
PI3K-Akt sig.ling pathway (hsa04151 )
AMPK sig.ling pathway (hsa04152 )
Insulin sig.ling pathway (hsa04910 )
Adipocytokine sig.ling pathway (hsa04920 )
Glucagon sig.ling pathway (hsa04922 )
Insulin resistance (hsa04931 )
Carbohydrate digestion and absorption (hsa04973 )
Reactome Pathway
Gluconeogenesis (R-HSA-70263 )
Severe congenital neutropenia type 4 (G6PC3) (R-HSA-3282872 )
BioCyc Pathway
MetaCyc:HS13873-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency DISX0DJD Definitive Autosomal recessive [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 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 Glucose-6-phosphatase 3 (G6PC3). [2]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Glucose-6-phosphatase 3 (G6PC3). [3]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Glucose-6-phosphatase 3 (G6PC3). [4]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Glucose-6-phosphatase 3 (G6PC3). [5]
Marinol DM70IK5 Approved Marinol increases the expression of Glucose-6-phosphatase 3 (G6PC3). [6]
Aspirin DM672AH Approved Aspirin increases the expression of Glucose-6-phosphatase 3 (G6PC3). [7]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Glucose-6-phosphatase 3 (G6PC3). [9]
Glyphosate DM0AFY7 Investigative Glyphosate decreases the expression of Glucose-6-phosphatase 3 (G6PC3). [10]
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⏷ Show the Full List of 8 Drug(s)
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 Glucose-6-phosphatase 3 (G6PC3). [8]
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References

1 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
2 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
3 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
4 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
5 Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
6 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
7 Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
8 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
9 Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
10 Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.