Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDFW5KH)

• DOT Name: Phosphatidylinositol N-acetylglucosaminyltransferase subunit C (PIGC)
• Synonyms: Phosphatidylinositol-glycan biosynthesis class C protein; PIG-C
• Gene Name: PIGC
• Related Disease:
  Parkinson disease
  Glycosylphosphatidylinositol biosynthesis defect 16
  Non-immune hydrops fetalis
  Autosomal recessive non-syndromic intellectual disability
  Intellectual disability
• UniProt ID: PIGC_HUMAN
• Pfam ID: PF06432
• Sequence:
  MYAQPVTNTKEVKWQKVLYERQPFPDNYVDRRFLEELRKNIHARKYQYWAVVFESSVVIQ
  QLCSVCVFVVIWWYMDEGLLAPHWLLGTGLASSLIGYVLFDLIDGGEGRKKSGQTRWADL
  KSALVFITFTYGFSPVLKTLTESVSTDTIYAMSVFMLLGHLIFFDYGANAAIVSSTLSLN
  MAIFASVCLASRLPRSLHAFIMVTFAIQIFALWPMLQKKLKACTPRSYVGVTLLFAFSAV
  GGLLSISAVGAVLFALLLMSISCLCPFYLIRLQLFKENIHGPWDEAEIKEDLSRFLS
• 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.
• 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

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Definitive	Biomarker	[1]
Glycosylphosphatidylinositol biosynthesis defect 16	DISNAPML	Strong	Autosomal recessive	[2]
Non-immune hydrops fetalis	DISPUY8C	Strong	Genetic Variation	[2]
Autosomal recessive non-syndromic intellectual disability	DISJWRZZ	Supportive	Autosomal recessive	[3]
Intellectual disability	DISMBNXP	Disputed	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Phosphatidylinositol N-acetylglucosaminyltransferase subunit C (PIGC).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit C (PIGC).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit C (PIGC).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit C (PIGC).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit C (PIGC).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit C (PIGC).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit C (PIGC).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit C (PIGC).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit C (PIGC).	[13]

References

• [1] Elucidating Conserved Transcriptional Networks Underlying Pesticide Exposure and Parkinson's Disease: A Focus on Chemicals of Epidemiological Relevance.Front Genet. 2019 Jan 25;9:701. doi: 10.3389/fgene.2018.00701. eCollection 2018.
• [2] Identification of embryonic lethal genes in humans by autozygosity mapping and exome sequencing in consanguineous families. Genome Biol. 2015 Jun 3;16(1):116. doi: 10.1186/s13059-015-0681-6.
• [3] Mutations in the phosphatidylinositol glycan C (PIGC) gene are associated with epilepsy and intellectual disability. J Med Genet. 2017 Mar;54(3):196-201. doi: 10.1136/jmedgenet-2016-104202. Epub 2016 Sep 30.
• [4] 1q24 deletion syndrome. Two cases and new insights into genotype-phenotype correlations.Am J Med Genet A. 2018 Sep;176(9):2004-2008. doi: 10.1002/ajmg.a.40426. Epub 2018 Aug 6.
• [5] 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.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [11] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.