Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUN0WC4)

• DOT Name: Phosphatidylinositol-glycan biosynthesis class X protein (PIGX)
• Synonyms: PIG-X
• Gene Name: PIGX
• Related Disease:
  Advanced cancer
  Bardet biedl syndrome
  Breast cancer
  Breast carcinoma
  Polydactyly
  Asthma
• UniProt ID: PIGX_HUMAN
• Pfam ID: PF08320
• Sequence:
  MAARVAAVRAAAWLLLGAATGLTRGPAAAFTAARSDAGIRAMCSEIILRQEVLKDGFHRD
  LLIKVKFGESIEDLHTCRLLIKQDIPAGLYVDPYELASLRERNITEAVMVSENFDIEAPN
  YLSKESEVLIYARRDSQCIDCFQAFLPVHCRYHRPHSEDGEASIVVNNPDLLMFCDQEFP
  ILKCWAHSEVAAPCALENEDICQWNKMKYKSVYKNVILQVPVGLTVHTSLVCSVTLLITI
  LCSTLILVAVFKYGHFSL
• Function: Essential component of glycosylphosphatidylinositol-mannosyltransferase 1 which transfers the first of the 4 mannoses in the GPI-anchor precursors during GPI-anchor biosynthesis. Probably acts by stabilizing the mannosyltransferase PIGM.
• 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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Bardet biedl syndrome	DISTBNZW	Strong	CausalMutation	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Polydactyly	DIS25BMZ	Strong	CausalMutation	[2]
Asthma	DISW9QNS	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Phosphatidylinositol-glycan biosynthesis class X protein (PIGX).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phosphatidylinositol-glycan biosynthesis class X protein (PIGX).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Phosphatidylinositol-glycan biosynthesis class X protein (PIGX).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Phosphatidylinositol-glycan biosynthesis class X protein (PIGX).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphatidylinositol-glycan biosynthesis class X protein (PIGX).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Phosphatidylinositol-glycan biosynthesis class X protein (PIGX).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phosphatidylinositol-glycan biosynthesis class X protein (PIGX).	[10]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Phosphatidylinositol-glycan biosynthesis class X protein (PIGX).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Phosphatidylinositol-glycan biosynthesis class X protein (PIGX).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Phosphatidylinositol-glycan biosynthesis class X protein (PIGX).	[14]

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 decreases the methylation of Phosphatidylinositol-glycan biosynthesis class X protein (PIGX).	[13]

References

• [1] Phosphatidylinositol glycan anchor biosynthesis, class X containing complex promotes cancer cell proliferation through suppression of EHD2 and ZIC1, putative tumor suppressors.Int J Oncol. 2016 Sep;49(3):868-76. doi: 10.3892/ijo.2016.3607. Epub 2016 Jul 6.
• [2] Homozygous mutation in CEP19, a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly. J Med Genet. 2018 Mar;55(3):189-197. doi: 10.1136/jmedgenet-2017-104758. Epub 2017 Nov 10.
• [3] A genome-wide cross-trait analysis from UK Biobank highlights the shared genetic architecture of asthma and allergic diseases.Nat Genet. 2018 Jun;50(6):857-864. doi: 10.1038/s41588-018-0121-0. Epub 2018 May 21.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] 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.
• [11] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.