Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI3B2HB)

• DOT Name: Phosphatidylinositol N-acetylglucosaminyltransferase subunit Y (PIGY)
• Synonyms: Phosphatidylinositol-glycan biosynthesis class Y protein; PIG-Y
• Gene Name: PIGY
• Related Disease:
  Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency
  Hyperphosphatasia-intellectual disability syndrome
  Hyperphosphatasia with intellectual disability syndrome 6
• UniProt ID: PIGY_HUMAN
• Pfam ID: PF15159
• Sequence:
  MFLSLPTLTVLIPLVSLAGLFYSASVEENFPQGCTSTASLCFYSLLLPITIPVYVFFHLW
  TWMGIKLFRHN
• Function: Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis. May act by regulating the catalytic subunit PIGA.
• KEGG Pathway:
  Glycosylphosphatidylinositol (GPI)-anchor biosynthesis (hsa00563)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of glycosylphosphatidylinositol (GPI) (R-HSA-162710)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	DISO56WE	Strong	Autosomal recessive	[1]
Hyperphosphatasia-intellectual disability syndrome	DISQJ9HK	Supportive	Autosomal recessive	[1]
Hyperphosphatasia with intellectual disability syndrome 6	DISVY45F	Limited	Autosomal recessive	[2]

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit Y (PIGY).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit Y (PIGY).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit Y (PIGY).	[6]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit Y (PIGY).	[7]

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 increases the methylation of Phosphatidylinositol N-acetylglucosaminyltransferase subunit Y (PIGY).	[5]

References

• [1] Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies. Hum Mol Genet. 2015 Nov 1;24(21):6146-59. doi: 10.1093/hmg/ddv331. Epub 2015 Aug 20.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [7] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.