Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNWT1WB)

DOT Name N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase (AGA)
Synonyms EC 3.5.1.26; Aspartylglucosaminidase; Glycosylasparaginase; N4-(N-acetyl-beta-glucosaminyl)-L-asparagine amidase
Gene Name AGA
Related Disease
Aspartylglucosaminuria ( )
Dermatitis herpetiformis ( )
Familial hypoparathyroidism ( )
Irritable bowel syndrome ( )
Schizophrenia ( )
Type-1 diabetes ( )
Type-1/2 diabetes ( )
Achalasia ( )
Alcoholic hepatitis ( )
Alopecia ( )
Androgenetic alopecia ( )
Attention deficit hyperactivity disorder ( )
Baldness, male pattern ( )
Cholecystitis ( )
Congenital disorder of glycosylation ( )
Dyspepsia ( )
Fetal growth restriction ( )
Gastric cancer ( )
Hepatocellular carcinoma ( )
Inflammatory bowel disease ( )
Influenza ( )
Liver cirrhosis ( )
Lysosomal storage disease ( )
Multiple sclerosis ( )
Primary sclerosing cholangitis ( )
Stomach cancer ( )
Ulcerative colitis ( )
Encephalitis ( )
Lupus nephritis ( )
Eosinophilic esophagitis ( )
Esophageal disorder ( )
Fabry disease ( )
Hepatitis C virus infection ( )
Human papillomavirus infection ( )
Neoplasm ( )
Tuberculosis ( )
UniProt ID
ASPG_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1APY; 1APZ
EC Number
3.5.1.26
Pfam ID
PF01112
Sequence
MARKSNLPVLLVPFLLCQALVRCSSPLPLVVNTWPFKNATEAAWRALASGGSALDAVESG
CAMCEREQCDGSVGFGGSPDELGETTLDAMIMDGTTMDVGAVGDLRRIKNAIGVARKVLE
HTTHTLLVGESATTFAQSMGFINEDLSTTASQALHSDWLARNCQPNYWRNVIPDPSKYCG
PYKPPGILKQDIPIHKETEDDRGHDTIGMVVIHKTGHIAAGTSTNGIKFKIHGRVGDSPI
PGAGAYADDTAGAAAATGNGDILMRFLPSYQAVEYMRRGEDPTIACQKVISRIQKHFPEF
FGAVICANVTGSYGAACNKLSTFTQFSFMVYNSEKNQPTEEKVDCI
Function Cleaves the GlcNAc-Asn bond which joins oligosaccharides to the peptide of asparagine-linked glycoproteins.
KEGG Pathway
Other glycan degradation (hsa00511 )
Lysosome (hsa04142 )
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
BioCyc Pathway
MetaCyc:HS00528-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Aspartylglucosaminuria DISZ3IBZ Definitive Autosomal recessive [1]
Dermatitis herpetiformis DIS0TC0G Definitive Biomarker [2]
Familial hypoparathyroidism DIS85C84 Definitive Genetic Variation [3]
Irritable bowel syndrome DIS27206 Definitive Biomarker [2]
Schizophrenia DISSRV2N Definitive Biomarker [4]
Type-1 diabetes DIS7HLUB Definitive Biomarker [2]
Type-1/2 diabetes DISIUHAP Definitive Biomarker [5]
Achalasia DISK845N Strong Genetic Variation [6]
Alcoholic hepatitis DISA7SH0 Strong Biomarker [7]
Alopecia DIS37HU4 Strong Biomarker [8]
Androgenetic alopecia DISSJR1P Strong Biomarker [9]
Attention deficit hyperactivity disorder DISL8MX9 Strong Biomarker [10]
Baldness, male pattern DIS9C9RO Strong Genetic Variation [11]
Cholecystitis DISG024R Strong Genetic Variation [12]
Congenital disorder of glycosylation DIS400QP Strong Biomarker [13]
Dyspepsia DISYEEY6 Strong Biomarker [14]
Fetal growth restriction DIS5WEJ5 Strong Biomarker [15]
Gastric cancer DISXGOUK Strong Biomarker [16]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [17]
Inflammatory bowel disease DISGN23E Strong Biomarker [18]
Influenza DIS3PNU3 Strong Biomarker [19]
Liver cirrhosis DIS4G1GX Strong Biomarker [20]
Lysosomal storage disease DIS6QM6U Strong Genetic Variation [21]
Multiple sclerosis DISB2WZI Strong Genetic Variation [22]
Primary sclerosing cholangitis DISTH5WJ Strong Biomarker [23]
Stomach cancer DISKIJSX Strong Biomarker [16]
Ulcerative colitis DIS8K27O Strong Biomarker [24]
Encephalitis DISLD1RL moderate Biomarker [25]
Lupus nephritis DISCVGPZ moderate Genetic Variation [26]
Eosinophilic esophagitis DISR8WSB Limited Biomarker [27]
Esophageal disorder DIS5L3HQ Limited Biomarker [28]
Fabry disease DISUUQJF Limited Altered Expression [29]
Hepatitis C virus infection DISQ0M8R Limited Biomarker [17]
Human papillomavirus infection DISX61LX Limited Genetic Variation [30]
Neoplasm DISZKGEW Limited Biomarker [31]
Tuberculosis DIS2YIMD Limited Genetic Variation [32]
------------------------------------------------------------------------------------
⏷ Show the Full List of 36 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 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 N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase (AGA). [33]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase (AGA). [34]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase (AGA). [35]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase (AGA). [36]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase (AGA). [37]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase (AGA). [38]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase (AGA). [39]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase (AGA). [40]
OXYQUINOLINE DMZVS9Y Investigative OXYQUINOLINE decreases the expression of N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase (AGA). [41]
------------------------------------------------------------------------------------
⏷ Show the Full List of 9 Drug(s)

References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Coeliac disease.Paediatr Int Child Health. 2019 Feb;39(1):23-31. doi: 10.1080/20469047.2018.1504431. Epub 2018 Aug 13.
3 Analysis of the preproPTH gene by denaturing gradient gel electrophoresis in familial isolated hypoparathyroidism.J Clin Endocrinol Metab. 1992 Mar;74(3):509-16. doi: 10.1210/jcem.74.3.1740484.
4 Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study.J Psychiatry Neurosci. 2019 Jul 1;44(4):269-276. doi: 10.1503/jpn.180174.
5 Association between maternal diabetes, being large for gestational age and breast-feeding on being overweight or obese in childhood.Diabetologia. 2019 Feb;62(2):249-258. doi: 10.1007/s00125-018-4758-0. Epub 2018 Nov 13.
6 Clinical Practice Update: The Use of Per-Oral Endoscopic Myotomy in Achalasia: Expert Review and Best Practice AdviceFrom the AGA Institute.Gastroenterology. 2017 Nov;153(5):1205-1211. doi: 10.1053/j.gastro.2017.10.001. Epub 2017 Oct 6.
7 Medical Management of Severe Alcoholic Hepatitis: ExpertReview from the Clinical Practice Updates Committee ofthe AGA Institute.Clin Gastroenterol Hepatol. 2017 Jan;15(1):5-12. doi: 10.1016/j.cgh.2016.08.047.
8 Clinical evaluation of a novel fractional radiofrequency device for hair growth: Fractional radiofrequency for hair growth stimulation.Dermatol Ther. 2018 May;31(3):e12590. doi: 10.1111/dth.12590. Epub 2018 Jan 15.
9 Evidence for two independent functional variants for androgenetic alopecia around the androgen receptor gene.Exp Dermatol. 2010 Nov;19(11):1026-8. doi: 10.1111/j.1600-0625.2010.01132.x. Epub 2010 Sep 7.
10 A long-term follow-up study of men born with very low birth weight and their reproductive hormone profile.Syst Biol Reprod Med. 2018 Jun;64(3):207-215. doi: 10.1080/19396368.2018.1448901. Epub 2018 Mar 27.
11 Evidence for a polygenic contribution to androgenetic alopecia.Br J Dermatol. 2013 Oct;169(4):927-30. doi: 10.1111/bjd.12443.
12 Small for gestational age as an independent risk factor for long-term pediatric gastrointestinal morbidity of the offspring().J Matern Fetal Neonatal Med. 2019 May;32(9):1407-1411. doi: 10.1080/14767058.2017.1406473. Epub 2017 Dec 4.
13 Elevation of plasma aspartylglucosaminidase is a useful marker for the congenital disorders of glycosylation type I (CDG I).J Inherit Metab Dis. 2005;28(6):1197-8. doi: 10.1007/s10545-005-0157-z.
14 White Paper AGA: Functional Dyspepsia.Clin Gastroenterol Hepatol. 2017 Aug;15(8):1191-1194. doi: 10.1016/j.cgh.2017.05.013. Epub 2017 May 18.
15 Advanced MRI analysis to detect white matter brain injury in growth restricted newborn lambs.Neuroimage Clin. 2019;24:101991. doi: 10.1016/j.nicl.2019.101991. Epub 2019 Aug 23.
16 Effects of selected genetic polymorphisms in xeroderma pigmentosum complementary group D on gastric cancer.Mol Biol Rep. 2011 Mar;38(3):1507-13. doi: 10.1007/s11033-010-0258-0. Epub 2010 Sep 15.
17 AGA Clinical Practice Update on Interaction Between Oral Direct-Acting Antivirals for Chronic Hepatitis C Infection and Hepatocellular Carcinoma: Expert Review.Gastroenterology. 2019 Jun;156(8):2149-2157. doi: 10.1053/j.gastro.2019.02.046. Epub 2019 Mar 13.
18 AGA Clinical Practice Update on Functional Gastrointestinal Symptoms in Patients With Inflammatory Bowel Disease: Expert Review.Clin Gastroenterol Hepatol. 2019 Feb;17(3):380-390.e1. doi: 10.1016/j.cgh.2018.08.001. Epub 2018 Aug 9.
19 Schizophrenia susceptibility genes directly implicated in the life cycles of pathogens: cytomegalovirus, influenza, herpes simplex, rubella, and Toxoplasma gondii.Schizophr Bull. 2009 Nov;35(6):1163-82. doi: 10.1093/schbul/sbn054. Epub 2008 Jun 13.
20 AGA Clinical Practice Update: Coagulation in Cirrhosis.Gastroenterology. 2019 Jul;157(1):34-43.e1. doi: 10.1053/j.gastro.2019.03.070. Epub 2019 Apr 12.
21 Amlexanox provides a potential therapy for nonsense mutations in the lysosomal storage disorder Aspartylglucosaminuria.Biochim Biophys Acta Mol Basis Dis. 2018 Mar;1864(3):668-675. doi: 10.1016/j.bbadis.2017.12.014. Epub 2017 Dec 13.
22 Myxovirus resistance protein A (MxA) polymorphism is associated with IFN response in Iranian multiple sclerosis patients.Neurol Sci. 2017 Jun;38(6):1093-1099. doi: 10.1007/s10072-017-2935-4. Epub 2017 Apr 6.
23 AGA Clinical Practice Update on Surveillance for Hepatobiliary Cancers in Patients With Primary Sclerosing Cholangitis: Expert Review.Clin Gastroenterol Hepatol. 2019 Nov;17(12):2416-2422. doi: 10.1016/j.cgh.2019.07.011. Epub 2019 Jul 12.
24 AGA Technical Review on the Management of Mild-to-Moderate Ulcerative Colitis.Gastroenterology. 2019 Feb;156(3):769-808.e29. doi: 10.1053/j.gastro.2018.12.008. Epub 2018 Dec 18.
25 Antigliadin Antibodies (AGA IgG) Are Related to Neurochemistry in Schizophrenia.Front Psychiatry. 2017 Jun 19;8:104. doi: 10.3389/fpsyt.2017.00104. eCollection 2017.
26 Detecting Genetic Associations between ATG5 and Lupus Nephritis by trans-eQTL.J Immunol Res. 2015;2015:153132. doi: 10.1155/2015/153132. Epub 2015 Oct 5.
27 White Paper AGA: Drug Development for Eosinophilic Esophagitis.Clin Gastroenterol Hepatol. 2017 Aug;15(8):1173-1183. doi: 10.1016/j.cgh.2017.03.016. Epub 2017 Mar 22.
28 Functional Lumen Imaging Probe for the Management of Esophageal Disorders: Expert Review From the Clinical Practice Updates Committee of the AGA Institute.Clin Gastroenterol Hepatol. 2017 Mar;15(3):325-334. doi: 10.1016/j.cgh.2016.10.022.
29 Development of a model system for neuronal dysfunction in Fabry disease.Mol Genet Metab. 2016 Sep;119(1-2):144-50. doi: 10.1016/j.ymgme.2016.07.010. Epub 2016 Jul 22.
30 The nonsynonymous single-nucleotide polymorphisms in codon 31 of p21 gene and the susceptibility to cervical cancer in Chinese women.Int J Gynecol Cancer. 2009 Aug;19(6):1011-4. doi: 10.1111/IGC.0b013e3181a8b950.
31 Fukuoka and AGA Criteria Have Superior Diagnostic Accuracy for Advanced Cystic Neoplasms than Sendai Criteria.Dig Dis Sci. 2017 Mar;62(3):626-632. doi: 10.1007/s10620-017-4460-y. Epub 2017 Jan 23.
32 Relationship between single nucleotide polymorphism of interleukin-18 and susceptibility to pulmonary tuberculosis in the Chinese Han population.Microbiol Immunol. 2011 Jun;55(6):388-93. doi: 10.1111/j.1348-0421.2011.00332.x.
33 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
34 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.
35 Gene expression data from acetaminophen-induced toxicity in human hepatic in vitro systems and clinical liver samples. Data Brief. 2016 Mar 26;7:1052-1057. doi: 10.1016/j.dib.2016.03.069. eCollection 2016 Jun.
36 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
37 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.
38 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
39 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
40 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
41 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.