Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2KJENI)

DOT Name Protein TFG (TFG)
Synonyms TRK-fused gene protein
Gene Name TFG
Related Disease
Chondrosarcoma ( )
Non-small-cell lung cancer ( )
Acute coronary syndrome ( )
Adult lymphoma ( )
Advanced cancer ( )
Anaplastic astrocytoma ( )
Anaplastic large cell lymphoma ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma ( )
Charcot marie tooth disease ( )
Charcot-Marie-Tooth disease type 2 ( )
Complex hereditary spastic paraplegia ( )
Craniosynostosis ( )
Diabetic kidney disease ( )
Glioblastoma multiforme ( )
Hereditary motor and sensory neuropathy ( )
Hereditary motor and sensory neuropathy, Okinawa type ( )
Hereditary spastic paraplegia ( )
Hereditary spastic paraplegia 57 ( )
High blood pressure ( )
Intellectual disability ( )
Lymphoma ( )
Malignant glioma ( )
Neoplasm ( )
Neuromuscular disease ( )
Pediatric lymphoma ( )
Peripheral neuropathy ( )
Small lymphocytic lymphoma ( )
Soft tissue neoplasm ( )
Thyroid gland carcinoma ( )
Thyroid gland papillary carcinoma ( )
Thyroid tumor ( )
Vascular purpura ( )
Prostate cancer ( )
Prostate carcinoma ( )
Autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation ( )
Bone osteosarcoma ( )
Colon cancer ( )
Colon carcinoma ( )
Melanoma ( )
Metastatic melanoma ( )
Osteosarcoma ( )
Type-1/2 diabetes ( )
UniProt ID
TFG_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00564
Sequence
MNGQLDLSGKLIIKAQLGEDIRRIPIHNEDITYDELVLMMQRVFRGKLLSNDEVTIKYKD
EDGDLITIFDSSDLSFAIQCSRILKLTLFVNGQPRPLESSQVKYLRRELIELRNKVNRLL
DSLEPPGEPGPSTNIPENDTVDGREEKSASDSSGKQSTQVMAASMSAFDPLKNQDEINKN
VMSAFGLTDDQVSGPPSAPAEDRSGTPDSIASSSSAAHPPGVQPQQPPYTGAQTQAGQIE
GQMYQQYQQQAGYGAQQPQAPPQQPQQYGIQYSASYSQQTGPQQPQQFQGYGQQPTSQAP
APAFSGQPQQLPAQPPQQYQASNYPAQTYTAQTSQPTNYTVAPASQPGMAPSQPGAYQPR
PGFTSLPGSTMTPPPSGPNPYARNRPPFGQGYTQPGPGYR
Function
Plays a role in the normal dynamic function of the endoplasmic reticulum (ER) and its associated microtubules. Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus.
Tissue Specificity Ubiquitous.
KEGG Pathway
Pathways in cancer (hsa05200 )
Thyroid cancer (hsa05216 )
Reactome Pathway
Signaling by ALK fusions and activated point mutants (R-HSA-9725370 )
COPII-mediated vesicle transport (R-HSA-204005 )

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Chondrosarcoma DIS4I7JB Definitive Biomarker [1]
Non-small-cell lung cancer DIS5Y6R9 Definitive Biomarker [2]
Acute coronary syndrome DIS7DYEW Strong Biomarker [3]
Adult lymphoma DISK8IZR Strong Biomarker [4]
Advanced cancer DISAT1Z9 Strong Altered Expression [5]
Anaplastic astrocytoma DISSBE0K Strong Genetic Variation [6]
Anaplastic large cell lymphoma DISP4D1R Strong Genetic Variation [7]
Breast cancer DIS7DPX1 Strong Altered Expression [8]
Breast carcinoma DIS2UE88 Strong Altered Expression [8]
Carcinoma DISH9F1N Strong Biomarker [9]
Charcot marie tooth disease DIS3BT2L Strong Genetic Variation [10]
Charcot-Marie-Tooth disease type 2 DISR30O9 Strong Genetic Variation [11]
Complex hereditary spastic paraplegia DIS9KXQY Strong Genetic Variation [12]
Craniosynostosis DIS6J405 Strong Altered Expression [13]
Diabetic kidney disease DISJMWEY Strong Biomarker [14]
Glioblastoma multiforme DISK8246 Strong Genetic Variation [6]
Hereditary motor and sensory neuropathy DISR0X2K Strong Genetic Variation [15]
Hereditary motor and sensory neuropathy, Okinawa type DISZ4EN1 Strong Autosomal dominant [16]
Hereditary spastic paraplegia DISGZQV1 Strong Genetic Variation [17]
Hereditary spastic paraplegia 57 DISLQ516 Strong Autosomal recessive [18]
High blood pressure DISY2OHH Strong Altered Expression [19]
Intellectual disability DISMBNXP Strong Biomarker [20]
Lymphoma DISN6V4S Strong Biomarker [4]
Malignant glioma DISFXKOV Strong Biomarker [21]
Neoplasm DISZKGEW Strong Biomarker [22]
Neuromuscular disease DISQTIJZ Strong Genetic Variation [23]
Pediatric lymphoma DIS51BK2 Strong Biomarker [4]
Peripheral neuropathy DIS7KN5G Strong Biomarker [12]
Small lymphocytic lymphoma DIS30POX Strong Biomarker [24]
Soft tissue neoplasm DISP2OHE Strong Biomarker [4]
Thyroid gland carcinoma DISMNGZ0 Strong Biomarker [25]
Thyroid gland papillary carcinoma DIS48YMM Strong Biomarker [26]
Thyroid tumor DISLVKMD Strong Altered Expression [4]
Vascular purpura DIS6ZZMF Strong Biomarker [17]
Prostate cancer DISF190Y moderate Altered Expression [27]
Prostate carcinoma DISMJPLE moderate Altered Expression [27]
Autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation DISLU0Y0 Supportive Autosomal dominant [11]
Bone osteosarcoma DIST1004 Limited Altered Expression [28]
Colon cancer DISVC52G Limited Genetic Variation [29]
Colon carcinoma DISJYKUO Limited Genetic Variation [29]
Melanoma DIS1RRCY Limited Genetic Variation [30]
Metastatic melanoma DISSL43L Limited Genetic Variation [30]
Osteosarcoma DISLQ7E2 Limited Altered Expression [28]
Type-1/2 diabetes DISIUHAP Limited Biomarker [31]
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⏷ Show the Full List of 44 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Protein TFG (TFG). [32]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Protein TFG (TFG). [38]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Protein TFG (TFG). [33]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Protein TFG (TFG). [34]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Protein TFG (TFG). [35]
Aspirin DM672AH Approved Aspirin increases the expression of Protein TFG (TFG). [36]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Protein TFG (TFG). [37]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Protein TFG (TFG). [39]
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⏷ Show the Full List of 6 Drug(s)

References

1 The TFG-TEC fusion gene created by the t(3;9) translocation in human extraskeletal myxoid chondrosarcomas encodes a more potent transcriptional activator than TEC.Carcinogenesis. 2012 Aug;33(8):1450-8. doi: 10.1093/carcin/bgs164. Epub 2012 May 11.
2 EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas.Lung Cancer. 2008 Aug;61(2):163-9. doi: 10.1016/j.lungcan.2007.12.013. Epub 2008 Feb 1.
3 Transforming Growth Factor Beta (TFG-) Concentration Isoforms are Diminished in Acute Coronary Syndrome.Cell Biochem Biophys. 2018 Sep;76(3):433-439. doi: 10.1007/s12013-018-0849-2. Epub 2018 Jul 12.
4 TFG, a target of chromosome translocations in lymphoma and soft tissue tumors, fuses to GPR128 in healthy individuals.Haematologica. 2010 Jan;95(1):20-6. doi: 10.3324/haematol.2009.011536. Epub 2009 Oct 1.
5 Indocyanine green-loaded hollow mesoporous silica nanoparticles as an activatable theranostic agent.Nanotechnology. 2017 May 5;28(18):185102. doi: 10.1088/1361-6528/aa66b0. Epub 2017 Apr 10.
6 Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas.J Transl Med. 2007 Dec 19;5:67. doi: 10.1186/1479-5876-5-67.
7 Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity.Am J Pathol. 2002 Apr;160(4):1487-94. doi: 10.1016/S0002-9440(10)62574-6.
8 Effects of tamoxifen on transcriptional level of transforming growth factor beta (TGF-beta) isoforms 1 and 2 in tumor tissue during primary treatment of patients with breast cancer.Anticancer Res. 2003 Jan-Feb;23(1A):223-9.
9 The expression of TLR pathway molecules in peripheral blood mononuclear cells and their relationship with tumor invasion and cytokine secretion in laryngeal carcinoma.Adv Med Sci. 2012 Jun 1;57(1):124-35. doi: 10.2478/v10039-011-0058-3.
10 Continuum of phenotypes in hereditary motor and sensory neuropathy with proximal predominance and Charcot-Marie-Tooth patients with TFG mutation.Am J Med Genet A. 2019 Aug;179(8):1507-1515. doi: 10.1002/ajmg.a.61184. Epub 2019 May 20.
11 A novel TFG mutation causes Charcot-Marie-Tooth disease type 2 and impairs TFG function. Neurology. 2014 Sep 2;83(10):903-12. doi: 10.1212/WNL.0000000000000758. Epub 2014 Aug 6.
12 A novel homozygous mutation of the TFG gene in a patient with early onset spastic paraplegia and later onset sensorimotor polyneuropathy.J Hum Genet. 2019 Feb;64(2):171-176. doi: 10.1038/s10038-018-0538-4. Epub 2018 Nov 22.
13 Combined therapy with melatonin and exendin-4 effectively attenuated the deterioration of renal function in rat cardiorenal syndrome.Am J Transl Res. 2017 Feb 15;9(2):214-229. eCollection 2017.
14 Expression of gremlin, a bone morphogenetic protein antagonist, in human diabetic nephropathy.Am J Kidney Dis. 2005 Jun;45(6):1034-9. doi: 10.1053/j.ajkd.2005.03.014.
15 Muscle pathology of hereditary motor and sensory neuropathy with proximal dominant involvement with TFG mutation.Muscle Nerve. 2019 Dec;60(6):739-744. doi: 10.1002/mus.26683. Epub 2019 Aug 30.
16 The TRK-fused gene is mutated in hereditary motor and sensory neuropathy with proximal dominant involvement. Am J Hum Genet. 2012 Aug 10;91(2):320-9. doi: 10.1016/j.ajhg.2012.07.014.
17 Pathogenic TFG Mutations Underlying Hereditary Spastic Paraplegia Impair Secretory Protein Trafficking and Axon Fasciculation.Cell Rep. 2018 Aug 28;24(9):2248-2260. doi: 10.1016/j.celrep.2018.07.081.
18 Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure. Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5091-6. doi: 10.1073/pnas.1217197110. Epub 2013 Mar 11.
19 Adjuvant strategies for prevention of glomerulosclerosis.Med Hypotheses. 2006;67(6):1277-96. doi: 10.1016/j.mehy.2004.11.048. Epub 2006 Jul 7.
20 Novel Genetic, Clinical, and Pathomechanistic Insights into TFG-Associated Hereditary Spastic Paraplegia.Hum Mutat. 2016 Nov;37(11):1157-1161. doi: 10.1002/humu.23060. Epub 2016 Aug 30.
21 Characterization and transduction of a retroviral vector encoding human interleukin-4 and herpes simplex virus-thymidine kinase for glioma tumor vaccine therapy.Cancer Gene Ther. 2000 Mar;7(3):486-94. doi: 10.1038/sj.cgt.7700140.
22 Resveratrol suppresses melanoma by inhibiting NF-B/miR-221 and inducing TFG expression.Arch Dermatol Res. 2017 Dec;309(10):823-831. doi: 10.1007/s00403-017-1784-6. Epub 2017 Sep 21.
23 HMSN-P caused by p.Pro285Leu mutation in TFG is not confined to patients with Far East ancestry.Neurobiol Aging. 2015 Mar;36(3):1606.e1-7. doi: 10.1016/j.neurobiolaging.2014.11.021. Epub 2014 Dec 16.
24 Transforming growth factor-beta and multidrug resistance in chronic lymphocytic leukemia.Med Oncol. 1999 Jul;16(2):110-8. doi: 10.1007/BF02785844.
25 Characterization and chromosomal mapping of the human TFG gene involved in thyroid carcinoma.Genomics. 1997 May 1;41(3):327-31. doi: 10.1006/geno.1997.4625.
26 Rearrangements of NTRK1 gene in papillary thyroid carcinoma.Mol Cell Endocrinol. 2010 May 28;321(1):44-9. doi: 10.1016/j.mce.2009.10.009. Epub 2009 Oct 31.
27 Identification of phosphorylated proteins involved in the oncogenesis of prostate cancer via Pin1-proteomic analysis.Prostate. 2012 May 1;72(6):626-37. doi: 10.1002/pros.21466. Epub 2011 Aug 1.
28 Estrogen-related receptor participates transforming growth factor- (TGF-) induced epithelial-mesenchymal transition of osteosarcoma cells.Cell Adh Migr. 2017 Jul 4;11(4):338-346. doi: 10.1080/19336918.2016.1221567. Epub 2016 Aug 17.
29 Association between interleukin-4R and TGF-1 gene polymorphisms and the risk of colorectal cancer in a Korean population.Colorectal Dis. 2010 Dec;12(12):1208-12. doi: 10.1111/j.1463-1318.2009.02080.x.
30 Identification of TFG (TRK-fused gene) as a putative metastatic melanoma tumor suppressor gene.Genes Chromosomes Cancer. 2012 May;51(5):452-61. doi: 10.1002/gcc.21932. Epub 2012 Jan 17.
31 Trk-fused gene (TFG) regulates pancreatic cell mass and insulin secretory activity.Sci Rep. 2017 Oct 12;7(1):13026. doi: 10.1038/s41598-017-13432-x.
32 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.
33 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.
34 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
35 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.
36 Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
37 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.
38 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.
39 Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.