Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBH6ZK1)

DOT Name	Mannose-6-phosphate isomerase (MPI)
Synonyms	EC 5.3.1.8; Phosphohexomutase; Phosphomannose isomerase; PMI
Gene Name	MPI
Related Disease	MPI-congenital disorder of glycosylation ( ) PMM2-congenital disorder of glycosylation ( ) SRD5A3-congenital disorder of glycosylation ( ) Acute myelogenous leukaemia ( ) Advanced cancer ( ) Alzheimer disease ( ) Blindness ( ) Campomelic dysplasia ( ) Cardiac failure ( ) Cardiovascular disease ( ) Chronic kidney disease ( ) Coagulation defect ( ) Congenital disorder of glycosylation ( ) Congestive heart failure ( ) Coronary atherosclerosis ( ) Craniometaphyseal dysplasia, autosomal dominant ( ) Cryptococcosis ( ) Cystic fibrosis ( ) Developmental and epileptic encephalopathy, 36 ( ) Dilated cardiomyopathy 1A ( ) Fetal growth restriction ( ) Glioma ( ) Hepatitis B virus infection ( ) High blood pressure ( ) Hyperinsulinemia ( ) Hypoglycemia ( ) Malignant glioma ( ) Malignant neoplasm ( ) Myocardial ischemia ( ) Non-alcoholic fatty liver disease ( ) Postpartum depression ( ) Protein-losing enteropathy ( ) Thrombocytopenia ( ) Coronary microvascular disease ( ) Homozygous familial hypercholesterolemia ( ) Neoplasm ( ) Anxiety ( ) Anxiety disorder ( ) Coronary heart disease ( ) Keratoconjunctivitis sicca ( ) Myocardial infarction ( ) Non-insulin dependent diabetes ( ) Post-traumatic stress disorder ( ) Spinocerebellar ataxia type 6 ( ) Type-1/2 diabetes ( )
UniProt ID	MPI_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	5.3.1.8
Pfam ID	PF01238 ; PF20511 ; PF20512
Sequence	MAAPRVFPLSCAVQQYAWGKMGSNSEVARLLASSDPLAQIAEDKPYAELWMGTHPRGDAK ILDNRISQKTLSQWIAENQDSLGSKVKDTFNGNLPFLFKVLSVETPLSIQAHPNKELAEK LHLQAPQHYPDANHKPEMAIALTPFQGLCGFRPVEEIVTFLKKVPEFQFLIGDEAATHLK QTMSHDSQAVASSLQSCFSHLMKSEKKVVVEQLNLLVKRISQQAAAGNNMEDIFGELLLQ LHQQYPGDIGCFAIYFLNLLTLKPGEAMFLEANVPHAYLKGDCVECMACSDNTVRAGLTP KFIDVPTLCEMLSYTPSSSKDRLFLPTRSQEDPYLSIYDPPVPDFTIMKTEVPGSVTEYK VLALDSASILLMVQGTVIASTPTTQTPIPLQRGGVLFIGANESVSLKLTEPKDLLIFRAC CLL
Function	Isomerase that catalyzes the interconversion of fructose-6-P and mannose-6-P and has a critical role in the supply of D-mannose derivatives required for many eukaryotic glycosylation reactions.
Tissue Specificity	Expressed in all tissues, but more abundant in heart, brain and skeletal muscle.
KEGG Pathway	Fructose and mannose metabolism (hsa00051 ) Amino sugar and nucleotide sugar metabolism (hsa00520 ) Metabolic pathways (hsa01100 ) Biosynthesis of cofactors (hsa01240 ) Biosynthesis of nucleotide sugars (hsa01250 )
Reactome Pathway	Synthesis of GDP-mannose (R-HSA-446205 ) Defective MPI causes MPI-CDG (R-HSA-4043916 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
MPI-congenital disorder of glycosylation	DISJ394F	Definitive	Autosomal recessive	[1]
PMM2-congenital disorder of glycosylation	DISZRBCA	Definitive	Altered Expression	[2]
SRD5A3-congenital disorder of glycosylation	DISGHPPC	Definitive	Autosomal recessive	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Blindness	DISTIM10	Strong	Biomarker	[7]
Campomelic dysplasia	DISVTW53	Strong	Biomarker	[8]
Cardiac failure	DISDC067	Strong	Genetic Variation	[9]
Cardiovascular disease	DIS2IQDX	Strong	Altered Expression	[10]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[11]
Coagulation defect	DIS9X3H6	Strong	Biomarker	[12]
Congenital disorder of glycosylation	DIS400QP	Strong	Biomarker	[13]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[9]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[14]
Craniometaphyseal dysplasia, autosomal dominant	DISU12OO	Strong	Biomarker	[8]
Cryptococcosis	DISDYDTK	Strong	Biomarker	[15]
Cystic fibrosis	DIS2OK1Q	Strong	Altered Expression	[16]
Developmental and epileptic encephalopathy, 36	DISG4MY5	Strong	Biomarker	[17]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[18]
Fetal growth restriction	DIS5WEJ5	Strong	Biomarker	[19]
Glioma	DIS5RPEH	Strong	Biomarker	[20]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[21]
High blood pressure	DISY2OHH	Strong	Biomarker	[22]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[23]
Hypoglycemia	DISRCKR7	Strong	Biomarker	[12]
Malignant glioma	DISFXKOV	Strong	Biomarker	[20]
Malignant neoplasm	DISS6SNG	Strong	Biomarker	[5]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[14]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[21]
Postpartum depression	DIS08UKE	Strong	Biomarker	[24]
Protein-losing enteropathy	DISM3WQO	Strong	Biomarker	[12]
Thrombocytopenia	DISU61YW	Strong	Altered Expression	[25]
Coronary microvascular disease	DISTU5VE	moderate	Altered Expression	[26]
Homozygous familial hypercholesterolemia	DISRCNCF	moderate	Genetic Variation	[27]
Neoplasm	DISZKGEW	Disputed	Biomarker	[28]
Anxiety	DISIJDBA	Limited	Biomarker	[29]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[29]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[30]
Keratoconjunctivitis sicca	DISNOENH	Limited	Genetic Variation	[31]
Myocardial infarction	DIS655KI	Limited	Biomarker	[32]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[33]
Post-traumatic stress disorder	DISHL1EY	Limited	Biomarker	[31]
Spinocerebellar ataxia type 6	DISH7224	Limited	Biomarker	[34]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[35]
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⏷ Show the Full List of 45 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

12 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 Mannose-6-phosphate isomerase (MPI).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mannose-6-phosphate isomerase (MPI).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mannose-6-phosphate isomerase (MPI).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mannose-6-phosphate isomerase (MPI).	[39]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mannose-6-phosphate isomerase (MPI).	[41]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mannose-6-phosphate isomerase (MPI).	[42]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Mannose-6-phosphate isomerase (MPI).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Mannose-6-phosphate isomerase (MPI).	[44]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Mannose-6-phosphate isomerase (MPI).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Mannose-6-phosphate isomerase (MPI).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Mannose-6-phosphate isomerase (MPI).	[47]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Mannose-6-phosphate isomerase (MPI).	[48]
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⏷ Show the Full List of 12 Drug(s)

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Mannose-6-phosphate isomerase (MPI).	[40]
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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	Phosphomannose isomerase inhibitors improve N-glycosylation in selected phosphomannomutase-deficient fibroblasts.J Biol Chem. 2011 Nov 11;286(45):39431-8. doi: 10.1074/jbc.M111.285502. Epub 2011 Sep 26.
3	Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy. J Clin Invest. 1998 Apr 1;101(7):1414-20. doi: 10.1172/JCI2350.
4	Lanthanide-doped nanoparticles conjugated with an anti-CD33 antibody and a p53-activating peptide for acute myeloid leukemia therapy.Biomaterials. 2018 Jun;167:132-142. doi: 10.1016/j.biomaterials.2018.03.025. Epub 2018 Mar 14.
5	Hepatic Hemangioma on SPECT Myocardial Perfusion Imaging.Clin Nucl Med. 2018 Jun;43(6):468-470. doi: 10.1097/RLU.0000000000002090.
6	Cyclooxygenase 2 RNA message abundance, stability, and hypervariability in sporadic Alzheimer neocortex.J Neurosci Res. 1997 Dec 15;50(6):937-45. doi: 10.1002/(SICI)1097-4547(19971215)50:6<937::AID-JNR4>3.0.CO;2-E.
7	Mannose supplements induce embryonic lethality and blindness in phosphomannose isomerase hypomorphic mice.FASEB J. 2014 Apr;28(4):1854-69. doi: 10.1096/fj.13-245514. Epub 2014 Jan 13.
8	Coronary microvascular dysfunction is associated with cardiac time intervals in women with angina and no obstructive coronary artery disease: An iPOWER substudy.Echocardiography. 2019 Jun;36(6):1110-1117. doi: 10.1111/echo.14356. Epub 2019 Apr 22.
9	Utility of nuclear stress imaging in predicting long-term outcomes one-year post CABG Surgery.J Nucl Cardiol. 2020 Dec;27(6):1970-1978. doi: 10.1007/s12350-018-01469-y. Epub 2018 Nov 5.
10	Analysis of mRNA from human heart tissue and putative applications in forensic molecular pathology.Forensic Sci Int. 2010 Dec 15;203(1-3):99-105. doi: 10.1016/j.forsciint.2010.07.005. Epub 2010 Aug 12.
11	Incremental prognostic value of SPECT-MPI in chronic kidney disease: A reclassification analysis.J Nucl Cardiol. 2018 Oct;25(5):1658-1673. doi: 10.1007/s12350-016-0756-0. Epub 2017 Jan 3.
12	Severe hypoglycemia as a presenting symptom of carbohydrate-deficient glycoprotein syndrome.J Pediatr. 1999 Dec;135(6):775-81. doi: 10.1016/s0022-3476(99)70103-4.
13	CDG Therapies: From Bench to Bedside.Int J Mol Sci. 2018 Apr 27;19(5):1304. doi: 10.3390/ijms19051304.
14	Contemporary Discrepancies of Stenosis Assessment by Computed Tomography and Invasive Coronary Angiography.Circ Cardiovasc Imaging. 2019 Feb;12(2):e007720. doi: 10.1161/CIRCIMAGING.118.007720.
15	Identification and characterization of the Cryptococcus neoformans phosphomannose isomerase-encoding gene, MAN1, and its impact on pathogenicity.Mol Microbiol. 2001 May;40(3):610-20. doi: 10.1046/j.1365-2958.2001.02401.x.
16	N-glycosylation augmentation of the cystic fibrosis epithelium improves Pseudomonas aeruginosa clearance.Am J Respir Cell Mol Biol. 2011 Jun;44(6):824-30. doi: 10.1165/rcmb.2009-0285OC. Epub 2010 Aug 6.
17	Seizures and stupor during intravenous mannose therapy in a patient with CDG syndrome type 1b (MPI-CDG).J Inherit Metab Dis. 2010 Dec;33 Suppl 3:S497-502. doi: 10.1007/s10545-010-9252-x. Epub 2011 Jan 16.
18	Prognostic value of left-ventricular systolic and diastolic dyssynchrony measured from gated SPECT MPI in patients with dilated cardiomyopathy.J Nucl Cardiol. 2020 Oct;27(5):1582-1591. doi: 10.1007/s12350-018-01468-z. Epub 2018 Nov 1.
19	Utility of the modified myocardial performance index in growth-restricted fetuses.Echocardiography. 2019 Oct;36(10):1895-1900. doi: 10.1111/echo.14489. Epub 2019 Oct 8.
20	Mannose phosphate isomerase regulates fibroblast growth factor receptor family signaling and glioma radiosensitivity. PLoS One. 2014 Oct 14;9(10):e110345.
21	Mannose Phosphate Isomerase and Mannose Regulate Hepatic Stellate Cell Activation and Fibrosis in Zebrafish and Humans.Hepatology. 2019 Dec;70(6):2107-2122. doi: 10.1002/hep.30677. Epub 2019 May 24.
22	Right Ventricular Tissue Doppler Myocardial Performance Index in Children with Pulmonary Hypertension: Relation to Invasive Hemodynamics.Pediatr Cardiol. 2018 Jan;39(1):98-104. doi: 10.1007/s00246-017-1733-3. Epub 2017 Oct 4.
23	Artemisia dracunculus L. extract ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture.Diabetes Obes Metab. 2014 Aug;16(8):728-38. doi: 10.1111/dom.12274. Epub 2014 Mar 10.
24	Promoting the well-being of mothers with multidisciplinary psychosocial interventions in the perinatal period.J Affect Disord. 2019 Mar 1;246:148-156. doi: 10.1016/j.jad.2018.12.028. Epub 2018 Dec 18.
25	Carbohydrate-deficient glycoprotein syndrome type 1 with profound thrombocytopenia and normal phosphomannomutase and phosphomannose isomerase activities.J Pediatr. 1998 Nov;133(5):697-700. doi: 10.1016/s0022-3476(98)70115-5.
26	Assessment of the relationship between coronary flow rates and myocardial perfusion abnormality in patients with nonobstructive coronary artery disease: an observational study in cardiac syndrome X and coronary slow flow.Nucl Med Commun. 2019 Nov;40(11):1122-1129. doi: 10.1097/MNM.0000000000001080.
27	2D-STI combined with gated (99)Tc(m)-MIBI MPI for the diagnosis of myocardial ischemia in hypercholesterolemia patients.Exp Ther Med. 2017 Aug;14(2):981-994. doi: 10.3892/etm.2017.4602. Epub 2017 Jun 14.
28	Mannose impairs tumour growth and enhances chemotherapy.Nature. 2018 Nov;563(7733):719-723. doi: 10.1038/s41586-018-0729-3. Epub 2018 Nov 21.
29	An Extract of Artemisia dracunculus L. Promotes Psychological Resilience in a Mouse Model of Depression.Oxid Med Cell Longev. 2018 May 13;2018:7418681. doi: 10.1155/2018/7418681. eCollection 2018.
30	Changes in Myocardial Native T(1) and T(2) After Exercise Stress: A Noncontrast CMR Pilot Study.JACC Cardiovasc Imaging. 2020 Mar;13(3):667-680. doi: 10.1016/j.jcmg.2019.05.019. Epub 2019 Jul 17.
31	Dysfunctional Coping Mechanisms Contribute to Dry Eye Symptoms.J Clin Med. 2019 Jun 24;8(6):901. doi: 10.3390/jcm8060901.
32	Survival benefit of coronary revascularization after myocardial perfusion SPECT: The role of ischemia.J Nucl Cardiol. 2021 Aug;28(4):1676-1687. doi: 10.1007/s12350-019-01932-4. Epub 2019 Nov 11.
33	Bioactives of Artemisia dracunculus L enhance cellular insulin signaling in primary human skeletal muscle culture.Metabolism. 2008 Jul;57(7 Suppl 1):S58-64. doi: 10.1016/j.metabol.2008.04.003.
34	Alternative splicing in the C-terminal tail of Cav2.1 is essential for preventing a neurological disease in mice.Hum Mol Genet. 2017 Aug 15;26(16):3094-3104. doi: 10.1093/hmg/ddx193.
35	Prognostic value of left ventricular mechanical dyssynchrony indices in long-standing type II diabetes mellitus with normal perfusion and left ventricular systolic functions on SPECT-MPI.J Nucl Cardiol. 2020 Oct;27(5):1640-1648. doi: 10.1007/s12350-018-1436-z. Epub 2018 Sep 12.
36	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
37	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
38	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
39	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.
40	Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
41	Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
42	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
43	Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
44	Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
45	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.
46	Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
47	Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
48	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.