Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO10SVP)

• DOT Name: GPI ethanolamine phosphate transferase 2 (PIGG)
• Synonyms: EC 2.-.-.-; GPI7 homolog; hGPI7; Phosphatidylinositol-glycan biosynthesis class G protein; PIG-G
• Gene Name: PIGG
• Related Disease:
  Intellectual disability, autosomal recessive 53
  Intellectual disability
• UniProt ID: PIGG_HUMAN
• EC Number: 2.-.-.-
• Pfam ID: PF01663 ; PF19316
• Sequence:
  MRLGSGTFATCCVAIEVLGIAVFLRGFFPAPVRSSARAEHGAEPPAPEPSAGASSNWTTL
  PPPLFSKVVIVLIDALRDDFVFGSKGVKFMPYTTYLVEKGASHSFVAEAKPPTVTMPRIK
  ALMTGSLPGFVDVIRNLNSPALLEDSVIRQAKAAGKRIVFYGDETWVKLFPKHFVEYDGT
  TSFFVSDYTEVDNNVTRHLDKVLKRGDWDILILHYLGLDHIGHISGPNSPLIGQKLSEMD
  SVLMKIHTSLQSKERETPLPNLLVLCGDHGMSETGSHGASSTEEVNTPLILISSAFERKP
  GDIRHPKHVQQTDVAATLAIALGLPIPKDSVGSLLFPVVEGRPMREQLRFLHLNTVQLSK
  LLQENVPSYEKDPGFEQFKMSERLHGNWIRLYLEEKHSEVLFNLGSKVLRQYLDALKTLS
  LSLSAQVAQYDIYSMMVGTVVVLEVLTLLLLSVPQALRRKAELEVPLSSPGFSLLFYLVI
  LVLSAVHVIVCTSAESSCYFCGLSWLAAGGVMVLASALLCVIVSVLTNVLVGGNTPRKNP
  MHPSSRWSELDLLILLGTAGHVLSLGASSFVEEEHQTWYFLVNTLCLALSQETYRNYFLG
  DDGEPPCGLCVEQGHDGATAAWQDGPGCDVLERDKGHGSPSTSEVLRGREKWMVLASPWL
  ILACCRLLRSLNQTGVQWAHRPDLGHWLTSSDHKAELSVLAALSLLVVFVLVQRGCSPVS
  KAALALGLLGVYCYRAAIGSVRFPWRPDSKDISKGIIEARFVYVFVLGILFTGTKDLLKS
  QVIAADFKLKTVGLWEIYSGLVLLAALLFRPHNLPVLAFSLLIQTLMTKFIWKPLRHDAA
  EITVMHYWFGQAFFYFQGNSNNIATVDISAGFVGLDTYVEIPAVLLTAFGTYAGPVLWAS
  HLVHFLSSETRSGSALSHACFCYALICSIPVFTYIVLVTSLRYHLFIWSVFSPKLLYEGM
  HLLITAAVCVFFTAMDQTRLTQS
• Function: Ethanolamine phosphate transferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers ethanolamine phosphate to the GPI second mannose.
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability, autosomal recessive 53	DISGGOYI	Strong	Autosomal recessive	[1]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of GPI ethanolamine phosphate transferase 2 (PIGG).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of GPI ethanolamine phosphate transferase 2 (PIGG).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of GPI ethanolamine phosphate transferase 2 (PIGG).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of GPI ethanolamine phosphate transferase 2 (PIGG).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of GPI ethanolamine phosphate transferase 2 (PIGG).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of GPI ethanolamine phosphate transferase 2 (PIGG).	[7]
Selenium	DM25CGV	Approved	Selenium decreases the expression of GPI ethanolamine phosphate transferase 2 (PIGG).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of GPI ethanolamine phosphate transferase 2 (PIGG).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of GPI ethanolamine phosphate transferase 2 (PIGG).	[8]

References

• [1] Pathogenic Variants in PIGG Cause Intellectual Disability with Seizures and Hypotonia. Am J Hum Genet. 2016 Apr 7;98(4):615-26. doi: 10.1016/j.ajhg.2016.02.007. Epub 2016 Mar 17.
• [2] Identification and In Silico Characterization of a Novel Point Mutation within the Phosphatidylinositol Glycan Anchor Biosynthesis Class G Gene in an Iranian Family with Intellectual Disability.J Mol Neurosci. 2019 Dec;69(4):538-545. doi: 10.1007/s12031-019-01376-y. Epub 2019 Aug 14.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.