Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOD93DQ)

• DOT Name: Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q (PIGQ)
• Synonyms: N-acetylglucosamyl transferase component GPI1; Phosphatidylinositol-glycan biosynthesis class Q protein; PIG-Q
• Gene Name: PIGQ
• Related Disease:
  Arthritis
  Developmental and epileptic encephalopathy, 77
  Epilepsy
  Epileptic encephalopathy
  Immunodeficiency
  Infantile epileptic-dyskinetic encephalopathy
  Myocardial infarction
  Infantile spasm
• UniProt ID: PIGQ_HUMAN
• Pfam ID: PF05024
• Sequence:
  MVLKAFFPTCCVSTDSGLLVGRWVPEQSSAVVLAVLHFPFIPIQVKQLLAQVRQASQVGV
  AVLGTWCHCRQEPEESLGRFLESLGAVFPHEPWLRLCRERGGTFWSCEATHRQAPTAPGA
  PGEDQVMLIFYDQRQVLLSQLHLPTVLPDRQAGATTASTGGLAAVFDTVARSEVLFRSDR
  FDEGPVRLSHWQSEGVEASILAELARRASGPICLLLASLLSLVSAVSACRVFKLWPLSFL
  GSKLSTCEQLRHRLEHLTLIFSTRKAENPAQLMRKANTVASVLLDVALGLMLLSWLHGRS
  RIGHLADALVPVADHVAEELQHLLQWLMGAPAGLKMNRALDQVLGRFFLYHIHLWISYIH
  LMSPFVEHILWHVGLSACLGLTVALSLLSDIIALLTFHIYCFYVYGARLYCLKIHGLSSL
  WRLFRGKKWNVLRQRVDSCSYDLDQLFIGTLLFTILLFLLPTTALYYLVFTLLRLLVVAV
  QGLIHLLVDLINSLPLYSLGLRLCRPYRLADKPTALQPRGAHLPPPQLWLPPQALLGRPV
  PQAVPWGAHLPLEAERGQAGLRELLARLAPPHGHSQPSALPGWHQLSWRMSCALWTLLCA
  PEHGRPCYHTLGLEVIGSEQMWGWPARLAALHHWHCLPWDPLPTCCGHHGGEHSNPRCPE
  HCPMPTLCTQVQRVRPPQQPQVEGWSPWGLPSGSALAVGVEGPCQDEPPSPRHPLAPSAE
  QHPASGGLKQSLTPVPSGPGPSLPEPHGVYLRMFPGEVAL
• 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)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Strong	Biomarker	[1]
Developmental and epileptic encephalopathy, 77	DIS9R1LS	Strong	Autosomal recessive	[2]
Epilepsy	DISBB28L	Strong	Biomarker	[3]
Epileptic encephalopathy	DISZOCA3	Strong	Genetic Variation	[2]
Immunodeficiency	DIS093I0	Strong	Biomarker	[1]
Infantile epileptic-dyskinetic encephalopathy	DISD2ZNC	Strong	Biomarker	[3]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[4]
Infantile spasm	DISZSKDG	Supportive	Autosomal dominant	[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 Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q (PIGQ).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q (PIGQ).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q (PIGQ).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q (PIGQ).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q (PIGQ).	[8]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q (PIGQ).	[10]

References

• [1] Adenosine 2a Receptor Signal Blockade of Murine Autoimmune Arthritis via Inhibition of Pathogenic Germinal Center-Follicular Helper T Cells.Arthritis Rheumatol. 2019 May;71(5):773-783. doi: 10.1002/art.40796. Epub 2019 Mar 25.
• [2] Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis. Hum Mol Genet. 2014 Jun 15;23(12):3200-11. doi: 10.1093/hmg/ddu030. Epub 2014 Jan 25.
• [3] PIGQ glycosylphosphatidylinositol-anchored protein deficiency: Characterizing the phenotype.Am J Med Genet A. 2019 Jul;179(7):1270-1275. doi: 10.1002/ajmg.a.61185. Epub 2019 May 30.
• [4] Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.Atherosclerosis. 2011 Mar;215(1):145-52. doi: 10.1016/j.atherosclerosis.2010.12.005. Epub 2010 Dec 15.
• [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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] 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.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] 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.
• [10] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.