General Information of Drug Off-Target (DOT) (ID: OT4WXPKW)

DOT Name Sphingolipid delta(4)-desaturase DES1 (DEGS1)
Synonyms EC 1.14.19.17; Cell migration-inducing gene 15 protein; Degenerative spermatocyte homolog 1; Dihydroceramide desaturase-1; Membrane lipid desaturase; Retinol isomerase; EC 5.2.1.-
Gene Name DEGS1
Related Disease
Leukodystrophy, hypomyelinating, 18 ( )
Acute intermittent hepatic porphyria ( )
Alzheimer disease ( )
Amyloidosis ( )
Carcinoma of esophagus ( )
Cardiovascular disease ( )
Colorectal carcinoma ( )
Depression ( )
Epilepsy ( )
Esophagitis ( )
Graves disease ( )
High blood pressure ( )
Kidney failure ( )
Leukodystrophy ( )
Mental disorder ( )
Myocardial infarction ( )
Nervous system disease ( )
Pneumonitis ( )
Polyneuropathy ( )
Prostate cancer ( )
Prostate neoplasm ( )
Type-1/2 diabetes ( )
Krabbe disease ( )
Metachromatic leukodystrophy ( )
Metastatic malignant neoplasm ( )
Adult glioblastoma ( )
Glioblastoma multiforme ( )
Hyperglycemia ( )
Metastatic melanoma ( )
Myelodysplastic syndrome with multilineage dysplasia ( )
Nervous system inflammation ( )
Osteopetrosis ( )
UniProt ID
DEGS1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
1.14.19.17; 5.2.1.-
Pfam ID
PF00487 ; PF08557
Sequence
MGSRVSREDFEWVYTDQPHADRRREILAKYPEIKSLMKPDPNLIWIIIMMVLTQLGAFYI
VKDLDWKWVIFGAYAFGSCINHSMTLAIHEIAHNAAFGNCKAMWNRWFGMFANLPIGIPY
SISFKRYHMDHHRYLGADGVDVDIPTDFEGWFFCTAFRKFIWVILQPLFYAFRPLFINPK
PITYLEVINTVAQVTFDILIYYFLGIKSLVYMLAASLLGLGLHPISGHFIAEHYMFLKGH
ETYSYYGPLNLLTFNVGYHNEHHDFPNIPGKSLPLVRKIAAEYYDNLPHYNSWIKVLYDF
VMDDTISPYSRMKRHQKGEMVLE
Function Has sphingolipid-delta-4-desaturase activity. Converts D-erythro-sphinganine to D-erythro-sphingosine (E-sphing-4-enine). Catalyzes the equilibrium isomerization of retinols.
Tissue Specificity Ubiquitous.
KEGG Pathway
Sphingolipid metabolism (hsa00600 )
Metabolic pathways (hsa01100 )
Sphingolipid sig.ling pathway (hsa04071 )
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
Sphingolipid de novo biosynthesis (R-HSA-1660661 )
BioCyc Pathway
MetaCyc:ENSG00000143753-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Leukodystrophy, hypomyelinating, 18 DISVO5F8 Definitive Autosomal recessive [1]
Acute intermittent hepatic porphyria DIS80J7E Strong Biomarker [2]
Alzheimer disease DISF8S70 Strong Biomarker [3]
Amyloidosis DISHTAI2 Strong Biomarker [3]
Carcinoma of esophagus DISS6G4D Strong Altered Expression [4]
Cardiovascular disease DIS2IQDX Strong Biomarker [5]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [6]
Depression DIS3XJ69 Strong Genetic Variation [7]
Epilepsy DISBB28L Strong Genetic Variation [8]
Esophagitis DISHVC9B Strong Biomarker [9]
Graves disease DISU4KOQ Strong Biomarker [10]
High blood pressure DISY2OHH Strong Biomarker [11]
Kidney failure DISOVQ9P Strong Biomarker [5]
Leukodystrophy DISVY1TT Strong Biomarker [1]
Mental disorder DIS3J5R8 Strong Genetic Variation [12]
Myocardial infarction DIS655KI Strong Biomarker [5]
Nervous system disease DISJ7GGT Strong Genetic Variation [13]
Pneumonitis DIS88E0K Strong Biomarker [14]
Polyneuropathy DISB9G3W Strong Genetic Variation [15]
Prostate cancer DISF190Y Strong Biomarker [16]
Prostate neoplasm DISHDKGQ Strong Biomarker [16]
Type-1/2 diabetes DISIUHAP Strong Biomarker [17]
Krabbe disease DIS6H1IB moderate Biomarker [18]
Metachromatic leukodystrophy DIS3OMWS moderate Biomarker [18]
Metastatic malignant neoplasm DIS86UK6 moderate Biomarker [19]
Adult glioblastoma DISVP4LU Limited Biomarker [20]
Glioblastoma multiforme DISK8246 Limited Biomarker [20]
Hyperglycemia DIS0BZB5 Limited Biomarker [21]
Metastatic melanoma DISSL43L Limited Biomarker [22]
Myelodysplastic syndrome with multilineage dysplasia DISFFCP3 Limited Biomarker [23]
Nervous system inflammation DISB3X5A Limited Biomarker [22]
Osteopetrosis DIS7GHNM Limited Biomarker [24]
------------------------------------------------------------------------------------
⏷ Show the Full List of 32 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Sphingolipid delta(4)-desaturase DES1 (DEGS1). [25]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Sphingolipid delta(4)-desaturase DES1 (DEGS1). [26]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Sphingolipid delta(4)-desaturase DES1 (DEGS1). [27]
Marinol DM70IK5 Approved Marinol increases the expression of Sphingolipid delta(4)-desaturase DES1 (DEGS1). [28]
Selenium DM25CGV Approved Selenium decreases the expression of Sphingolipid delta(4)-desaturase DES1 (DEGS1). [29]
Piroxicam DMTK234 Approved Piroxicam increases the expression of Sphingolipid delta(4)-desaturase DES1 (DEGS1). [30]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate decreases the expression of Sphingolipid delta(4)-desaturase DES1 (DEGS1). [31]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Sphingolipid delta(4)-desaturase DES1 (DEGS1). [32]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Sphingolipid delta(4)-desaturase DES1 (DEGS1). [33]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Sphingolipid delta(4)-desaturase DES1 (DEGS1). [34]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Sphingolipid delta(4)-desaturase DES1 (DEGS1). [35]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Sphingolipid delta(4)-desaturase DES1 (DEGS1). [36]
Nickel chloride DMI12Y8 Investigative Nickel chloride decreases the expression of Sphingolipid delta(4)-desaturase DES1 (DEGS1). [37]
Resorcinol DMM37C0 Investigative Resorcinol increases the expression of Sphingolipid delta(4)-desaturase DES1 (DEGS1). [38]
------------------------------------------------------------------------------------
⏷ Show the Full List of 14 Drug(s)

References

1 Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy. J Clin Invest. 2019 Mar 1;129(3):1240-1256. doi: 10.1172/JCI123959. Epub 2019 Feb 11.
2 Qualitative and quantitative evaluation for morphological changes of the splenic artery in autoimmune pancreatitis: novel imaging findings for differentiation from pancreatic adenocarcinoma.Abdom Radiol (NY). 2018 Dec;43(12):3357-3366. doi: 10.1007/s00261-018-1634-9.
3 Dihydroceramide Desaturase 1 Inhibitors Reduce Amyloid- Levels in Primary Neurons from an Alzheimer's Disease Transgenic Model.Pharm Res. 2018 Feb 6;35(3):49. doi: 10.1007/s11095-017-2312-2.
4 Overexpression of degenerative spermatocyte homolog 1 up-regulates the expression of cyclin D1 and enhances metastatic efficiency in esophageal carcinoma Eca109 cells.Mol Carcinog. 2009 Oct;48(10):886-94. doi: 10.1002/mc.20533.
5 Predicted 10-year risk of cardiovascular mortality in the 40 to 69 year old general population without cardiovascular diseases in Germany.PLoS One. 2018 Jan 2;13(1):e0190441. doi: 10.1371/journal.pone.0190441. eCollection 2018.
6 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.
7 Respondents' report of a clinician-diagnosed depression in health surveys: comparison with DSM-IV mental disorders in the general adult population in Germany.BMC Psychiatry. 2017 Jan 23;17(1):39. doi: 10.1186/s12888-017-1203-8.
8 Outcome of Early Juvenile Onset Metachromatic Leukodystrophy After Unrelated Cord Blood Transplantation: A Case Series and Review of the Literature.J Child Neurol. 2016 Mar;31(3):338-44. doi: 10.1177/0883073815595078. Epub 2015 Jul 17.
9 Decision analytic modeling for the economic analysis of proton radiotherapy for non-small cell lung cancer.Transl Lung Cancer Res. 2018 Apr;7(2):122-133. doi: 10.21037/tlcr.2018.03.27.
10 Immunoglobulin activation of T cell chemoattractant expression in fibroblasts from patients with Graves' disease is mediated through the insulin-like growth factor I receptor pathway.J Immunol. 2003 Jun 15;170(12):6348-54. doi: 10.4049/jimmunol.170.12.6348.
11 Dietary Acid Load and Potassium Intake Associate with Blood Pressure and Hypertension Prevalence in a Representative Sample of the German Adult Population.Nutrients. 2018 Jan 19;10(1):103. doi: 10.3390/nu10010103.
12 Cognitive functioning in the general population: Factor structure and association with mental disorders-The neuropsychological test battery of the mental health module of the German Health Interview and Examination Survey for Adults (DEGS1-MH).Int J Methods Psychiatr Res. 2018 Mar;27(1):e1594. doi: 10.1002/mpr.1594. Epub 2017 Nov 6.
13 DEGS1 variant causes neurological disorder. Eur J Hum Genet. 2019 Nov;27(11):1668-1676. doi: 10.1038/s41431-019-0444-z. Epub 2019 Jun 11.
14 Correlation of Functional Lung Heterogeneity and Dosimetry to Radiation Pneumonitis using Perfusion SPECT/CT and FDG PET/CT Imaging.Int J Radiat Oncol Biol Phys. 2018 Nov 15;102(4):1255-1264. doi: 10.1016/j.ijrobp.2018.05.051. Epub 2018 Jun 1.
15 Adult-onset MLD: a gene mutation with isolated polyneuropathy.Neurology. 2000 Oct 10;55(7):1036-9. doi: 10.1212/wnl.55.7.1036.
16 Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
17 CCL2/MCP-1 and CXCL12/SDF-1 blockade by L-aptamers improve pancreatic islet engraftment and survival in mouse.Am J Transplant. 2019 Nov;19(11):3131-3138. doi: 10.1111/ajt.15518. Epub 2019 Jul 18.
18 Gene therapy for metachromatic leukodystrophy.J Neurosci Res. 2016 Nov;94(11):1169-79. doi: 10.1002/jnr.23792.
19 Cell cycle-coupled expansion of AR activity promotes cancer progression.Oncogene. 2017 Mar 23;36(12):1655-1668. doi: 10.1038/onc.2016.334. Epub 2016 Sep 26.
20 Dihydroceramide desaturase inhibitors induce autophagy via dihydroceramide-dependent and independent mechanisms.Biochim Biophys Acta Gen Subj. 2017 Feb;1861(2):264-275. doi: 10.1016/j.bbagen.2016.11.033. Epub 2016 Nov 25.
21 Cichoric acid improved hyperglycaemia and restored muscle injury via activating antioxidant response in MLD-STZ-induced diabetic mice.Food Chem Toxicol. 2017 Sep;107(Pt A):138-149. doi: 10.1016/j.fct.2017.06.041. Epub 2017 Jun 26.
22 The roles of Galectin-3 in autoimmunity and tumor progression.Immunol Res. 2012 Apr;52(1-2):100-10. doi: 10.1007/s12026-012-8286-6.
23 Differences in the bone marrow histology between childhood myelodysplastic syndrome with multilineage dysplasia and refractory cytopenia of childhood without multilineage dysplasia.Histopathology. 2019 Jan;74(2):239-247. doi: 10.1111/his.13721. Epub 2018 Oct 29.
24 Haploidentical bone marrow transplantation in leukemia and genetic diseases.Haematologica. 2000 Nov;85(11 Suppl):37-40.
25 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
26 Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
27 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.
28 Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization. Autophagy. 2016 Nov;12(11):2213-2229. doi: 10.1080/15548627.2016.1213927. Epub 2016 Sep 16.
29 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
30 Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
31 CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
32 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
33 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
34 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
35 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
36 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
37 The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
38 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.