Details of Drug Off-Target (DOT)

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

DOT Name Metaxin-1 (MTX1)
Synonyms Mitochondrial outer membrane import complex protein 1
Gene Name MTX1
Related Disease
Autoimmune disease ( )
B-cell lymphoma ( )
Psoriasis ( )
Psoriatic arthritis ( )
Pulmonary disease ( )
Stomach cancer ( )
Acute leukaemia ( )
Arthritis ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Central nervous system lymphoma ( )
Childhood acute lymphoblastic leukemia ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal adenocarcinoma ( )
Colorectal cancer ( )
Colorectal cancer, susceptibility to, 1 ( )
Colorectal cancer, susceptibility to, 10 ( )
Colorectal cancer, susceptibility to, 12 ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
Gastric cancer ( )
Graft-versus-host disease ( )
Juvenile idiopathic arthritis ( )
Lung adenocarcinoma ( )
Lung carcinoma ( )
Lung squamous cell carcinoma ( )
Neoplasm ( )
Osteosarcoma ( )
Ovarian neoplasm ( )
Ovarian serous adenocarcinoma ( )
Prostate carcinoma ( )
Systemic lupus erythematosus ( )
Acute lymphocytic leukaemia ( )
Anemia ( )
Leukopenia ( )
Lymphoproliferative syndrome ( )
Thrombocytopenia ( )
Gastrointestinal mucositis ( )
Hepatocellular carcinoma ( )
Leukemia ( )
Lymphoma ( )
Non-hodgkin lymphoma ( )
Parkinson disease ( )
UniProt ID
MTX1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF17171 ; PF10568
Sequence
MLLGGPPRSPRSGTSPKGPWSSTGHVQFGKSPQTWPRRTRPRSPEPAAPSGVRGSTWTRR
RDSPRRAGPTALSRYVGHLWMGRRPPSPEARGPVPRSSAASRARRSLASPGISPGPLTAT
IGGAVAGGGPRQGRAEAHKEVFPGQRVGKMAAPMELFCWSGGWGLPSVDLDSLAVLTYAR
FTGAPLKVHKISNPWQSPSGTLPALRTSHGEVISVPHKIITHLRKEKYNADYDLSARQGA
DTLAFMSLLEEKLLPVLVHTFWIDTKNYVEVTRKWYAEAMPFPLNFFLPGRMQRQYMERL
QLLTGEHRPEDEEELEKELYREARECLTLLSQRLGSQKFFFGDAPASLDAFVFSYLALLL
QAKLPSGKLQVHLRGLHNLCAYCTHILSLYFPWDGAEVPPQRQTPAGPETEEEPYRRRNQ
ILSVLAGLAAMVGYALLSGIVSIQRATPARAPGTRTLGMAEEDEEE
Function Involved in transport of proteins into the mitochondrion. Essential for embryonic development.
KEGG Pathway
Mitophagy - animal (hsa04137 )
Reactome Pathway
Cristae formation (R-HSA-8949613 )
RAC2 GTPase cycle (R-HSA-9013404 )
Mitochondrial protein import (R-HSA-1268020 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autoimmune disease DISORMTM Definitive Biomarker [1]
B-cell lymphoma DISIH1YQ Definitive Biomarker [2]
Psoriasis DIS59VMN Definitive Biomarker [3]
Psoriatic arthritis DISLWTG2 Definitive Biomarker [4]
Pulmonary disease DIS6060I Definitive Biomarker [5]
Stomach cancer DISKIJSX Definitive Genetic Variation [6]
Acute leukaemia DISDQFDI Strong Genetic Variation [7]
Arthritis DIST1YEL Strong Biomarker [8]
Bone osteosarcoma DIST1004 Strong Biomarker [9]
Breast cancer DIS7DPX1 Strong Biomarker [10]
Breast carcinoma DIS2UE88 Strong Genetic Variation [11]
Central nervous system lymphoma DISBYQTA Strong Biomarker [12]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Biomarker [13]
Colon cancer DISVC52G Strong Genetic Variation [11]
Colon carcinoma DISJYKUO Strong Biomarker [14]
Colorectal adenocarcinoma DISPQOUB Strong Genetic Variation [15]
Colorectal cancer DISNH7P9 Strong Genetic Variation [11]
Colorectal cancer, susceptibility to, 1 DISZ794C Strong Genetic Variation [11]
Colorectal cancer, susceptibility to, 10 DISQXMYM Strong Genetic Variation [11]
Colorectal cancer, susceptibility to, 12 DIS4FXJX Strong Genetic Variation [11]
Colorectal carcinoma DIS5PYL0 Strong Genetic Variation [11]
Colorectal neoplasm DISR1UCN Strong Genetic Variation [11]
Gastric cancer DISXGOUK Strong Altered Expression [16]
Graft-versus-host disease DIS0QADF Strong Genetic Variation [17]
Juvenile idiopathic arthritis DISQZGBV Strong Biomarker [18]
Lung adenocarcinoma DISD51WR Strong Genetic Variation [11]
Lung carcinoma DISTR26C Strong Genetic Variation [11]
Lung squamous cell carcinoma DISXPIBD Strong Genetic Variation [11]
Neoplasm DISZKGEW Strong Biomarker [19]
Osteosarcoma DISLQ7E2 Strong Biomarker [9]
Ovarian neoplasm DISEAFTY Strong Genetic Variation [11]
Ovarian serous adenocarcinoma DISSU72Z Strong Genetic Variation [11]
Prostate carcinoma DISMJPLE Strong Genetic Variation [11]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [20]
Acute lymphocytic leukaemia DISPX75S moderate Biomarker [13]
Anemia DISTVL0C moderate Biomarker [21]
Leukopenia DISJMBMM moderate Genetic Variation [21]
Lymphoproliferative syndrome DISMVL8O moderate Biomarker [22]
Thrombocytopenia DISU61YW moderate Genetic Variation [21]
Gastrointestinal mucositis DIS140OB Limited Biomarker [23]
Hepatocellular carcinoma DIS0J828 Limited Genetic Variation [15]
Leukemia DISNAKFL Limited Genetic Variation [24]
Lymphoma DISN6V4S Limited Genetic Variation [25]
Non-hodgkin lymphoma DISS2Y8A Limited Genetic Variation [26]
Parkinson disease DISQVHKL Limited Genetic Variation [27]
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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
5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Metaxin-1 (MTX1). [28]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Metaxin-1 (MTX1). [29]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Metaxin-1 (MTX1). [30]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Metaxin-1 (MTX1). [31]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Metaxin-1 (MTX1). [34]
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2 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 increases the methylation of Metaxin-1 (MTX1). [32]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Metaxin-1 (MTX1). [33]
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References

1 EBV-associated diffuse large B-cell lymphoma in a psoriatic treated with methotrexate.Pathol Res Pract. 2009;205(1):43-9. doi: 10.1016/j.prp.2008.08.006. Epub 2008 Oct 31.
2 Preparation and Characterization of Fe(3)O(4)@MTX Magnetic Nanoparticles for Thermochemotherapy of Primary Central Nervous System Lymphoma in vitro and in vivo.Int J Nanomedicine. 2019 Dec 5;14:9647-9663. doi: 10.2147/IJN.S205456. eCollection 2019.
3 In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.Int J Biol Macromol. 2018 Apr 15;110:259-268. doi: 10.1016/j.ijbiomac.2018.01.036. Epub 2018 Feb 2.
4 Differential synovial tissue biomarkers among psoriatic arthritis and rheumatoid factor/anti-citrulline antibody-negative rheumatoid arthritis.Arthritis Res Ther. 2019 May 9;21(1):116. doi: 10.1186/s13075-019-1898-7.
5 Methotrexate and interstitial lung disease: controversies and questions. A narrative review of the literature.Rheumatology (Oxford). 2019 Nov 1;58(11):1900-1906. doi: 10.1093/rheumatology/kez337.
6 Meta-analysis of genome-wide association studies and functional assays decipher susceptibility genes for gastric cancer in Chinese populations.Gut. 2020 Apr;69(4):641-651. doi: 10.1136/gutjnl-2019-318760. Epub 2019 Aug 5.
7 ABCB1 polymorphisms correlate with susceptibility to adult acute leukemia and response to high-dose methotrexate.Tumour Biol. 2015 Sep;36(10):7599-606. doi: 10.1007/s13277-015-3403-5. Epub 2015 Apr 29.
8 Venlafaxine alleviates complete Freund's adjuvant-induced arthritis in rats: Modulation of STAT-3/IL-17/RANKL axis.Life Sci. 2019 Jun 1;226:68-76. doi: 10.1016/j.lfs.2019.03.063. Epub 2019 Mar 28.
9 Outpatient High-dose Methotrexate for Osteosarcoma: It's Safe and Feasible, If You Want It.J Pediatr Hematol Oncol. 2019 Jul;41(5):394-398. doi: 10.1097/MPH.0000000000001238.
10 High-dose methotrexate in Egyptian pediatric acute lymphoblastic leukemia: the impact of ABCG2 C421A genetic polymorphism on plasma levels, what is next?.J Cancer Res Clin Oncol. 2014 Aug;140(8):1359-65. doi: 10.1007/s00432-014-1670-y. Epub 2014 Apr 10.
11 Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.Cancer Res. 2016 Sep 1;76(17):5103-14. doi: 10.1158/0008-5472.CAN-15-2980. Epub 2016 Apr 20.
12 Risk of death, relapse or progression, and loss of life expectancy at different progression-free survival milestones in primary central nervous system lymphoma.Leuk Lymphoma. 2019 Oct;60(10):2516-2523. doi: 10.1080/10428194.2019.1594219. Epub 2019 Apr 3.
13 Identification of Risk Factors in High-Dose Methotrexate-Induced Acute Kidney Injury in Childhood Acute Lymphoblastic Leukemia.Chemotherapy. 2018 Apr 19;63(2):101-107. doi: 10.1159/000486823. Online ahead of print.
14 Overexpression of S100A4 in human cancer cell lines resistant to methotrexate. BMC Cancer. 2010 Jun 1;10:250. doi: 10.1186/1471-2407-10-250.
15 Indospicine cytotoxicity and transport in human cell lines.Food Chem. 2018 Nov 30;267:119-123. doi: 10.1016/j.foodchem.2017.08.029. Epub 2017 Aug 8.
16 Association of high-evidence gastric cancer susceptibility loci and somatic gene expression levels with survival.Carcinogenesis. 2017 Oct 26;38(11):1119-1128. doi: 10.1093/carcin/bgx090.
17 Posttransplant cyclophosphamide vs cyclosporin A and methotrexate as GVHD prophylaxis in matched sibling transplantation.Blood Adv. 2019 Nov 12;3(21):3351-3359. doi: 10.1182/bloodadvances.2019000236.
18 Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti-Tumor Necrosis Factor Therapy inChildren With Polyarticular Forms of Juvenile IdiopathicArthritis With Clinically Inactive Disease.Arthritis Rheumatol. 2018 Sep;70(9):1508-1518. doi: 10.1002/art.40509. Epub 2018 Jul 25.
19 Histone deacetylase inhibitor reverses multidrug resistance by attenuating the nucleophosmin level through PI3K/Akt pathway in breast cancer.Int J Oncol. 2016 Jul;49(1):294-304. doi: 10.3892/ijo.2016.3528. Epub 2016 May 17.
20 Cervical neoplasia in systemic lupus erythematosus: a nationwide study.Rheumatology (Oxford). 2017 Apr 1;56(4):613-619. doi: 10.1093/rheumatology/kew459.
21 Cytopenias among patients with rheumatic diseases using methotrexate: a meta-analysis of randomized controlled clinical trials.Rheumatology (Oxford). 2020 Apr 1;59(4):709-717. doi: 10.1093/rheumatology/kez343.
22 Distinct patterns of lymphocyte count transition in lymphoproliferative disorder in patients with rheumatoid arthritis treated with methotrexate.Rheumatology (Oxford). 2017 Jun 1;56(6):940-946. doi: 10.1093/rheumatology/kex002.
23 MTHFR variant is associated with high-dose methotrexate-induced toxicity in the Chinese osteosarcoma patients.J Bone Oncol. 2018 Nov 1;13:143-147. doi: 10.1016/j.jbo.2018.10.002. eCollection 2018 Nov.
24 A Previously Unknown Drug-Drug Interaction Is Suspected in Delayed Elimination of Plasma Methotrexate in High-Dose Methotrexate Therapy.Ann Pharmacother. 2020 Jan;54(1):29-35. doi: 10.1177/1060028019870445. Epub 2019 Aug 15.
25 Methotrexate-associated lymphoproliferative disorder in the stomach and duodenum: a case report.BMC Gastroenterol. 2019 Apr 25;19(1):62. doi: 10.1186/s12876-019-0982-4.
26 SLCO1B1 rs4149056 genetic polymorphism predicting methotrexate toxicity in Chinese patients with non-Hodgkin lymphoma.Pharmacogenomics. 2017 Nov;18(17):1557-1562. doi: 10.2217/pgs-2017-0110. Epub 2017 Nov 2.
27 Homozygosity for the MTX1 c.184T>A (p.S63T) alteration modifies the age of onset in GBA-associated Parkinson's disease.Neurogenetics. 2011 Nov;12(4):325-32. doi: 10.1007/s10048-011-0293-6. Epub 2011 Aug 12.
28 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.
29 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
30 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
31 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.
32 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.
33 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
34 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.