Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXC27FL)

• DOT Name: Sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 (DEGS2)
• Synonyms: EC 1.14.18.5; EC 1.14.19.17; Degenerative spermatocyte homolog 2; Sphingolipid 4-desaturase; Sphingolipid C4-monooxygenase
• Gene Name: DEGS2
• Related Disease:
  Cognitive impairment
  Colorectal carcinoma
  HIV infectious disease
  Mental disorder
  Schizophrenia
  Type-1/2 diabetes
• UniProt ID: DEGS2_HUMAN
• EC Number: 1.14.18.5; 1.14.19.17
• Pfam ID: PF00487 ; PF08557
• Sequence:
  MGNSASRSDFEWVYTDQPHTQRRKEILAKYPAIKALMRPDPRLKWAVLVLVLVQMLACWL
  VRGLAWRWLLFWAYAFGGCVNHSLTLAIHDISHNAAFGTGRAARNRWLAVFANLPVGVPY
  AASFKKYHVDHHRYLGGDGLDVDVPTRLEGWFFCTPARKLLWLVLQPFFYSLRPLCVHPK
  AVTRMEVLNTLVQLAADLAIFALWGLKPVVYLLASSFLGLGLHPISGHFVAEHYMFLKGH
  ETYSYYGPLNWITFNVGYHVEHHDFPSIPGYNLPLVRKIAPEYYDHLPQHHSWVKVLWDF
  VFEDSLGPYARVKRVYRLAKDGL
• Function: Bifunctional enzyme which acts both as a sphingolipid delta(4)-desaturase and a sphingolipid C4-monooxygenase.
• Tissue Specificity: Highly expressed in skin, intestine and kidney.
• KEGG Pathway:
  Sphingolipid metabolism (hsa00600)
  Metabolic pathways (hsa01100)
  Sphingolipid sig.ling pathway (hsa04071)
• Reactome Pathway: Sphingolipid de novo biosynthesis (R-HSA-1660661)
• BioCyc Pathway: MetaCyc:HS15665-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
HIV infectious disease	DISO97HC	Strong	Biomarker	[3]
Mental disorder	DIS3J5R8	Strong	Altered Expression	[1]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 (DEGS2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 (DEGS2).	[5]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 (DEGS2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 (DEGS2).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 (DEGS2).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 (DEGS2).	[7]

References

• [1] DEGS2 polymorphism associated with cognition in schizophrenia is associated with gene expression in brain.Transl Psychiatry. 2015 Apr 14;5(4):e550. doi: 10.1038/tp.2015.45.
• [2] The key genes underlying pathophysiology association between the type 2-diabetic and colorectal cancer.J Cell Physiol. 2018 Nov;233(11):8551-8557. doi: 10.1002/jcp.26440. Epub 2018 Jun 15.
• [3] Reconnaissance of the candidate genes involved in the pathogenesis of human immunodeficiency virus and targeted by antiretroviral therapy.J Med Virol. 2019 Dec;91(12):2134-2141. doi: 10.1002/jmv.25549. Epub 2019 Jul 30.
• [4] 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.
• [5] 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.
• [6] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.