Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZWU3FU)

DOT Name Matrix Gla protein (MGP)
Synonyms MGP; Cell growth-inhibiting gene 36 protein
Gene Name MGP
Related Disease
Atherosclerosis ( )
Glioblastoma multiforme ( )
Intellectual disability ( )
Keutel syndrome ( )
Knee osteoarthritis ( )
Adenocarcinoma ( )
Adult glioblastoma ( )
Advanced cancer ( )
Arteriosclerosis ( )
Breast cancer ( )
Breast carcinoma ( )
Calciphylaxis ( )
Cardiac failure ( )
Chronic kidney disease ( )
Clear cell renal carcinoma ( )
Colitis ( )
Congestive heart failure ( )
Crohn disease ( )
Diabetic kidney disease ( )
Estrogen-receptor positive breast cancer ( )
Glaucoma/ocular hypertension ( )
Melanoma ( )
Metabolic disorder ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Obstructive sleep apnea ( )
Osteoarthritis ( )
Osteoporosis ( )
Pseudoxanthoma elasticum ( )
Renal cell carcinoma ( )
Triple negative breast cancer ( )
Type-1/2 diabetes ( )
Classic Hodgkin lymphoma ( )
Huntington disease ( )
Nephropathy ( )
Chronic renal failure ( )
End-stage renal disease ( )
Undifferentiated carcinoma ( )
Carcinoma ( )
Chronic obstructive pulmonary disease ( )
Colorectal carcinoma ( )
Non-insulin dependent diabetes ( )
Smith-McCort dysplasia 1 ( )
Varicose veins ( )
Vascular disease ( )
UniProt ID
MGP_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MKSLILLAILAALAVVTLCYESHESMESYELNPFINRRNANTFISPQQRWRAKVQERIRE
RSKPVHELNREACDDYRLCERYAMVYGYNAAYNRYFRKRRGTK
Function Associates with the organic matrix of bone and cartilage. Thought to act as an inhibitor of bone formation.

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Atherosclerosis DISMN9J3 Definitive Biomarker [1]
Glioblastoma multiforme DISK8246 Definitive Biomarker [2]
Intellectual disability DISMBNXP Definitive Biomarker [3]
Keutel syndrome DISV1U6H Definitive Autosomal recessive [4]
Knee osteoarthritis DISLSNBJ Definitive Genetic Variation [5]
Adenocarcinoma DIS3IHTY Strong Altered Expression [6]
Adult glioblastoma DISVP4LU Strong Altered Expression [7]
Advanced cancer DISAT1Z9 Strong Altered Expression [8]
Arteriosclerosis DISK5QGC Strong Biomarker [1]
Breast cancer DIS7DPX1 Strong Biomarker [9]
Breast carcinoma DIS2UE88 Strong Biomarker [9]
Calciphylaxis DIS2Y594 Strong Biomarker [10]
Cardiac failure DISDC067 Strong Biomarker [11]
Chronic kidney disease DISW82R7 Strong Biomarker [12]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [13]
Colitis DISAF7DD Strong Biomarker [14]
Congestive heart failure DIS32MEA Strong Biomarker [11]
Crohn disease DIS2C5Q8 Strong Biomarker [14]
Diabetic kidney disease DISJMWEY Strong Genetic Variation [15]
Estrogen-receptor positive breast cancer DIS1H502 Strong Altered Expression [16]
Glaucoma/ocular hypertension DISLBXBY Strong Biomarker [17]
Melanoma DIS1RRCY Strong Biomarker [18]
Metabolic disorder DIS71G5H Strong Altered Expression [19]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [20]
Neoplasm DISZKGEW Strong Biomarker [21]
Obstructive sleep apnea DIS0SVD1 Strong Biomarker [22]
Osteoarthritis DIS05URM Strong Altered Expression [23]
Osteoporosis DISF2JE0 Strong Biomarker [24]
Pseudoxanthoma elasticum DIS8WUQG Strong Biomarker [25]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [13]
Triple negative breast cancer DISAMG6N Strong Biomarker [26]
Type-1/2 diabetes DISIUHAP Strong Altered Expression [27]
Classic Hodgkin lymphoma DISV1LU6 moderate Biomarker [28]
Huntington disease DISQPLA4 moderate Biomarker [28]
Nephropathy DISXWP4P moderate Genetic Variation [15]
Chronic renal failure DISGG7K6 Disputed Altered Expression [29]
End-stage renal disease DISXA7GG Disputed Altered Expression [29]
Undifferentiated carcinoma DISIAZST Disputed Biomarker [30]
Carcinoma DISH9F1N Limited Altered Expression [31]
Chronic obstructive pulmonary disease DISQCIRF Limited Biomarker [32]
Colorectal carcinoma DIS5PYL0 Limited Altered Expression [8]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [27]
Smith-McCort dysplasia 1 DIS8072R Limited Biomarker [33]
Varicose veins DISIMBN2 Limited Altered Expression [34]
Vascular disease DISVS67S Limited Genetic Variation [35]
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⏷ Show the Full List of 45 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
24 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Matrix Gla protein (MGP). [36]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Matrix Gla protein (MGP). [37]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Matrix Gla protein (MGP). [38]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Matrix Gla protein (MGP). [39]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Matrix Gla protein (MGP). [40]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Matrix Gla protein (MGP). [41]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Matrix Gla protein (MGP). [42]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Matrix Gla protein (MGP). [43]
Triclosan DMZUR4N Approved Triclosan increases the expression of Matrix Gla protein (MGP). [44]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Matrix Gla protein (MGP). [45]
Progesterone DMUY35B Approved Progesterone decreases the expression of Matrix Gla protein (MGP). [46]
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the expression of Matrix Gla protein (MGP). [47]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Matrix Gla protein (MGP). [48]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Matrix Gla protein (MGP). [49]
Dasatinib DMJV2EK Approved Dasatinib increases the expression of Matrix Gla protein (MGP). [50]
Phytonadione DM8HDOL Approved Phytonadione increases the expression of Matrix Gla protein (MGP). [51]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Matrix Gla protein (MGP). [52]
Coprexa DMA0WEK Phase 3 Coprexa increases the expression of Matrix Gla protein (MGP). [53]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Matrix Gla protein (MGP). [54]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Matrix Gla protein (MGP). [55]
Afimoxifene DMFORDT Phase 2 Afimoxifene decreases the expression of Matrix Gla protein (MGP). [47]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Matrix Gla protein (MGP). [57]
Coumarin DM0N8ZM Investigative Coumarin decreases the expression of Matrix Gla protein (MGP). [58]
Choline DM5D9YK Investigative Choline affects the expression of Matrix Gla protein (MGP). [59]
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⏷ Show the Full List of 24 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Matrix Gla protein (MGP). [56]
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References

1 Subclinical atherosclerosis is linked to small intestinal bacterial overgrowth via vitamin K2-dependent mechanisms.World J Gastroenterol. 2017 Feb 21;23(7):1241-1249. doi: 10.3748/wjg.v23.i7.1241.
2 Epigenetic silencing of Id4 identifies a glioblastoma subgroup with a better prognosis as a consequence of an inhibition of angiogenesis.Cancer. 2013 Mar 1;119(5):1004-12. doi: 10.1002/cncr.27821. Epub 2012 Nov 6.
3 Role of Wdr45b in maintaining neural autophagy and cognitive function.Autophagy. 2020 Apr;16(4):615-625. doi: 10.1080/15548627.2019.1632621. Epub 2019 Jun 25.
4 A novel MGP mutation in a consanguineous family: review of the clinical and molecular characteristics of Keutel syndrome. Am J Med Genet A. 2005 May 15;135(1):36-40. doi: 10.1002/ajmg.a.30680.
5 Genetic association analysis of Osteopontin and Matrix Gla Protein genes polymorphisms with primary knee osteoarthritis in Mexican population.Clin Rheumatol. 2019 Jan;38(1):223-228. doi: 10.1007/s10067-018-4146-7. Epub 2018 May 18.
6 Down-regulation of matrix Gla protein messenger RNA in human colorectal adenocarcinomas.Cancer Lett. 2001 Apr 10;165(1):63-9. doi: 10.1016/s0304-3835(01)00416-5.
7 Matrix gla protein (MGP): an overexpressed and migration-promoting mesenchymal component in glioblastoma.BMC Cancer. 2009 Aug 27;9:302. doi: 10.1186/1471-2407-9-302.
8 Evaluation of MGP gene expression in colorectal cancer.Gene. 2020 Jan 10;723:144120. doi: 10.1016/j.gene.2019.144120. Epub 2019 Oct 4.
9 Downregulation of matrix Gla protein is a biomarker for tamoxifen-resistant and radioresistant breast cancer.Biomark Med. 2019 Jul;13(10):841-850. doi: 10.2217/bmm-2019-0050. Epub 2019 Jul 18.
10 Warfarin in nonvalvular atrial fibrillation-Time for a change?.Semin Dial. 2019 Nov;32(6):520-526. doi: 10.1111/sdi.12829. Epub 2019 Jun 17.
11 Daily Supplementation with 4000 IU Vitamin D3 for Three Years Does Not Modify Cardiovascular Risk Markers in Patients with Advanced Heart Failure: The Effect of Vitamin D on Mortality in Heart Failure Trial.Ann Nutr Metab. 2019;74(1):62-68. doi: 10.1159/000495662. Epub 2018 Dec 14.
12 Evaluation of inactive Matrix-Gla-Protein (MGP) as a biomarker for incident and recurrent kidney stones.J Nephrol. 2020 Feb;33(1):101-107. doi: 10.1007/s40620-019-00623-0. Epub 2019 Jun 20.
13 Expression of the matrix Gla protein in urogenital malignancies.Int J Cancer. 1992 Oct 21;52(4):534-7. doi: 10.1002/ijc.2910520406.
14 Mesenchymal stromal cells-derived matrix Gla protein contribute to the alleviation of experimental colitis.Cell Death Dis. 2018 Jun 7;9(6):691. doi: 10.1038/s41419-018-0734-3.
15 Matrix Gla protein T-138C polymorphism is associated with carotid intima media thickness and predicts mortality in patients with diabetic nephropathy.J Diabetes Complications. 2017 Oct;31(10):1527-1532. doi: 10.1016/j.jdiacomp.2017.06.012. Epub 2017 Jun 30.
16 MGP is downregulated due to promoter methylation in chemoresistant ER+ breast cancer and high MGP expression predicts better survival outcomes.Eur Rev Med Pharmacol Sci. 2017 Oct;21(17):3871-3878.
17 A single gene connects stiffness in glaucoma and the vascular system.Exp Eye Res. 2017 May;158:13-22. doi: 10.1016/j.exer.2016.08.022. Epub 2016 Sep 1.
18 Expression analysis of genes identified by molecular profiling of VGP melanomas and MGP melanoma-positive lymph nodes.Cancer Biol Ther. 2004 Jan;3(1):110-20. doi: 10.4161/cbt.3.1.662. Epub 2004 Jan 24.
19 Pseudoxanthoma elasticum: molecular genetics and putative pathomechanisms. J Invest Dermatol. 2010 Mar;130(3):661-70. doi: 10.1038/jid.2009.411. Epub 2009 Dec 24.
20 Overexpression of matrix Gla protein mRNA in malignant human breast cells: isolation by differential cDNA hybridization.Oncogene. 1990 Sep;5(9):1391-5.
21 Microneedle-Based Generation of Microbubbles in Cancer Tumors to Improve Ultrasound-Assisted Drug Delivery.Adv Healthc Mater. 2019 Sep;8(17):e1900613. doi: 10.1002/adhm.201900613. Epub 2019 Jul 22.
22 Bone metabolism parameters and inactive matrix Gla protein in patients with obstructive sleep apnea?"Vilovic M. Ticinovic Kurir T
23 Expression analysis of the osteoarthritis genetic susceptibility mapping to the matrix Gla protein gene MGP.Arthritis Res Ther. 2019 Jun 18;21(1):149. doi: 10.1186/s13075-019-1934-7.
24 Assay for human matrix gla protein in serum: potential applications in the cardiovascular field.Arterioscler Thromb Vasc Biol. 2000 May;20(5):1257-61. doi: 10.1161/01.atv.20.5.1257.
25 Matrix gla protein and alkaline phosphatase are differently modulated in human dermal fibroblasts from PXE patients and controls.J Invest Dermatol. 2013 Apr;133(4):946-54. doi: 10.1038/jid.2012.460. Epub 2012 Dec 6.
26 Upregulation of MGP by HOXC8 promotes the proliferation, migration, and EMT processes of triple-negative breast cancer.Mol Carcinog. 2019 Oct;58(10):1863-1875. doi: 10.1002/mc.23079. Epub 2019 Jul 1.
27 Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus.Am J Hypertens. 2017 Feb;30(2):196-201. doi: 10.1093/ajh/hpw146. Epub 2016 Dec 7.
28 Altered Mineral Metabolism and Disequilibrium Between Calcification Promoters and Inhibitors in Chronic Hemodialysis Patients.Biol Trace Elem Res. 2020 Jan;193(1):14-22. doi: 10.1007/s12011-019-01685-8. Epub 2019 Mar 7.
29 Renal matrix Gla protein expression increases progressively with CKD and predicts renal outcome.Exp Mol Pathol. 2018 Aug;105(1):120-129. doi: 10.1016/j.yexmp.2018.07.001. Epub 2018 Jul 6.
30 Global gene expression profiling of chemically induced rat mammary gland carcinomas and adenomas.Toxicol Pathol. 2005;33(7):768-75. doi: 10.1080/01926230500437027.
31 Gene expression profiling to identify markers associated with deregulated hTERT in HPV-transformed keratinocytes and cervical cancer.Int J Cancer. 2008 Feb 15;122(4):877-88. doi: 10.1002/ijc.23210.
32 Low Vitamin K Status Is Associated with Increased Elastin Degradation in Chronic Obstructive Pulmonary Disease.J Clin Med. 2019 Jul 27;8(8):1116. doi: 10.3390/jcm8081116.
33 Dissecting Molecular Mechanisms Underlying Pulmonary Vascular Smooth Muscle Cell Dedifferentiation in Pulmonary Hypertension: Role of Mutated Caveolin-1 (Cav1(F92A))-Bone Marrow Mesenchymal Stem Cells.Heart Lung Circ. 2019 Oct;28(10):1587-1597. doi: 10.1016/j.hlc.2018.08.002. Epub 2018 Sep 7.
34 Identification of differentially expressed genes in human varicose veins: involvement of matrix gla protein in extracellular matrix remodeling.J Vasc Res. 2007;44(6):444-59. doi: 10.1159/000106189. Epub 2007 Jul 20.
35 Serum total matrix Gla protein: Reference interval in healthy adults and variations in patients with vascular and osteoarticular diseases.Clin Chim Acta. 2019 Mar;490:128-134. doi: 10.1016/j.cca.2018.12.029. Epub 2018 Dec 28.
36 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.
37 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.
38 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
39 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
40 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
41 Analysis of estrogen agonism and antagonism of tamoxifen, raloxifene, and ICI182780 in endometrial cancer cells: a putative role for the epidermal growth factor receptor ligand amphiregulin. J Soc Gynecol Investig. 2005 Oct;12(7):e55-67.
42 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.
43 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
44 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
45 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.
46 Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
47 Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells. J Cell Biochem. 2006 Aug 1;98(5):1163-84.
48 Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
49 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
50 Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
51 Vitamin K1 Inhibition of Renal Crystal Formation through Matrix Gla Protein in the Kidney. Kidney Blood Press Res. 2019;44(6):1392-1403. doi: 10.1159/000503300. Epub 2019 Oct 22.
52 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.
53 Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
54 Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
55 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.
56 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
57 Editor's Highlight: Transcriptome Profiling Reveals Bisphenol A Alternatives Activate Estrogen Receptor Alpha in Human Breast Cancer Cells. Toxicol Sci. 2017 Aug 1;158(2):431-443. doi: 10.1093/toxsci/kfx101.
58 Relation of circulating Matrix Gla-Protein and anticoagulation status in patients with aortic valve calcification. Thromb Haemost. 2009 Apr;101(4):706-13.
59 Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not. Am J Clin Nutr. 2007 Jul;86(1):230-9. doi: 10.1093/ajcn/86.1.230.