Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZX703K)

• DOT Name: CDP-diacylglycerol--inositol 3-phosphatidyltransferase (CDIPT)
• Synonyms: EC 2.7.8.11; Phosphatidylinositol synthase; PI synthase; PtdIns synthase
• Gene Name: CDIPT
• Related Disease:
  46,XX testicular disorder of sex development
  Disorder of sexual differentiation
  Myasthenia gravis
• UniProt ID: CDIPT_HUMAN
• EC Number: 2.7.8.11
• Pfam ID: PF01066
• Sequence:
  MPDENIFLFVPNLIGYARIVFAIISFYFMPCCPLTASSFYLLSGLLDAFDGHAARALNQG
  TRFGAMLDMLTDRCSTMCLLVNLALLYPGATLFFQISMSLDVASHWLHLHSSVVRGSESH
  KMIDLSGNPVLRIYYTSRPALFTLCAGNELFYCLLYLFHFSEGPLVGSVGLFRMGLWVTA
  PIALLKSLISVIHLITAARNMAALDAADRAKKK
• Function: Catalyzes the biosynthesis of phosphatidylinositol (PtdIns) as well as PtdIns:inositol exchange reaction. May thus act to reduce an excessive cellular PtdIns content. The exchange activity is due to the reverse reaction of PtdIns synthase and is dependent on CMP, which is tightly bound to the enzyme.
• Tissue Specificity: Detected in placenta (at protein level). Widely expressed. Higher expression in adult liver and skeletal muscle, slightly lower levels seen in pancreas, kidney, lung, placenta, brain, heart, leukocyte, colon, small intestine, ovary, testis, prostate, thymus and spleen. In fetus, expressed in kidney, liver, lung and brain.
• KEGG Pathway:
  Inositol phosphate metabolism (hsa00562)
  Glycerophospholipid metabolism (hsa00564)
  Metabolic pathways (hsa01100)
  Phosphatidylinositol sig.ling system (hsa04070)
• Reactome Pathway: Synthesis of PI (R-HSA-1483226)
• BioCyc Pathway: MetaCyc:HS02513-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
46,XX testicular disorder of sex development	DISTZBTV	Strong	Genetic Variation	[1]
Disorder of sexual differentiation	DISRMAEZ	Strong	Genetic Variation	[1]
Myasthenia gravis	DISELRCI	Limited	Genetic Variation	[2]

1 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 CDP-diacylglycerol--inositol 3-phosphatidyltransferase (CDIPT).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of CDP-diacylglycerol--inositol 3-phosphatidyltransferase (CDIPT).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CDP-diacylglycerol--inositol 3-phosphatidyltransferase (CDIPT).	[5]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of CDP-diacylglycerol--inositol 3-phosphatidyltransferase (CDIPT).	[6]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of CDP-diacylglycerol--inositol 3-phosphatidyltransferase (CDIPT).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of CDP-diacylglycerol--inositol 3-phosphatidyltransferase (CDIPT).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of CDP-diacylglycerol--inositol 3-phosphatidyltransferase (CDIPT).	[9]

References

• [1] Ovarian-specific expression of a new gene regulated by the goat PIS region and transcribed by a FOXL2 bidirectional promoter.Genomics. 2005 Jun;85(6):715-26. doi: 10.1016/j.ygeno.2005.02.011.
• [2] Rituximab as induction therapy in refractory myasthenia gravis: 18month follow-up study.J Neurol. 2019 Jul;266(7):1596-1600. doi: 10.1007/s00415-019-09296-y. Epub 2019 Mar 27.
• [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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [7] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.