Details of Drug Off-Target (DOT)

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

• DOT Name: Myogenin (MYOG)
• Synonyms: Class C basic helix-loop-helix protein 3; bHLHc3; Myogenic factor 4; Myf-4
• Gene Name: MYOG
• Related Disease:
  Advanced cancer
  Alveolar soft part sarcoma
  Chondrosarcoma
  Chronic fatigue syndrome
  Congenital myopathy
  Familial dilated cardiomyopathy
  Malignant soft tissue neoplasm
  Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4
  Myopathy
  Myotonic dystrophy
  Neoplasm
  Osteoarthritis
  Proteus syndrome
  Respiratory failure
  Sarcoma
  Spinal muscular atrophy
  Age-related macular degeneration
  Neuroblastoma
  Myasthenia gravis
  Obesity
  Osteoporosis
• UniProt ID: MYOG_HUMAN
• Pfam ID: PF01586 ; PF00010
• Sequence:
  MELYETSPYFYQEPRFYDGENYLPVHLQGFEPPGYERTELTLSPEAPGPLEDKGLGTPEH
  CPGQCLPWACKVCKRKSVSVDRRRAATLREKRRLKKVNEAFEALKRSTLLNPNQRLPKVE
  ILRSAIQYIERLQALLSSLNQEERDLRYRGGGGPQPGVPSECSSHSASCSPEWGSALEFS
  ANPGDHLLTADPTDAHNLHSLTSIVDSITVEDVSVAFPDETMPN
• Function: Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation, cell cycle exit and muscle atrophy. Essential for the development of functional embryonic skeletal fiber muscle differentiation. However is dispensable for postnatal skeletal muscle growth; phosphorylation by CAMK2G inhibits its transcriptional activity in respons to muscle activity. Required for the recruitment of the FACT complex to muscle-specific promoter regions, thus promoting gene expression initiation. During terminal myoblast differentiation, plays a role as a strong activator of transcription at loci with an open chromatin structure previously initiated by MYOD1. Together with MYF5 and MYOD1, co-occupies muscle-specific gene promoter core regions during myogenesis. Cooperates also with myocyte-specific enhancer factor MEF2D and BRG1-dependent recruitment of SWI/SNF chromatin-remodeling enzymes to alter chromatin structure at myogenic late gene promoters. Facilitates cell cycle exit during terminal muscle differentiation through the up-regulation of miR-20a expression, which in turn represses genes involved in cell cycle progression. Binds to the E-box containing (E1) promoter region of the miR-20a gene. Plays also a role in preventing reversal of muscle cell differentiation. Contributes to the atrophy-related gene expression in adult denervated muscles. Induces fibroblasts to differentiate into myoblasts.
• Reactome Pathway: Myogenesis (R-HSA-525793)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alveolar soft part sarcoma	DISLKJKZ	Strong	Biomarker	[2]
Chondrosarcoma	DIS4I7JB	Strong	Biomarker	[3]
Chronic fatigue syndrome	DIS34WJ5	Strong	Altered Expression	[4]
Congenital myopathy	DISLSK9G	Strong	Genetic Variation	[5]
Familial dilated cardiomyopathy	DISBHDU9	Strong	Biomarker	[6]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[7]
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4	DISGM0K5	Strong	Altered Expression	[8]
Myopathy	DISOWG27	Strong	Altered Expression	[9]
Myotonic dystrophy	DISNBEMX	Strong	Altered Expression	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[12]
Proteus syndrome	DISJ3VXH	Strong	Biomarker	[13]
Respiratory failure	DISVMYJO	Strong	Genetic Variation	[5]
Sarcoma	DISZDG3U	Strong	Biomarker	[7]
Spinal muscular atrophy	DISTLKOB	Strong	Biomarker	[14]
Age-related macular degeneration	DIS0XS2C	moderate	Biomarker	[15]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[16]
Myasthenia gravis	DISELRCI	Limited	Biomarker	[17]
Obesity	DIS47Y1K	Limited	Biomarker	[18]
Osteoporosis	DISF2JE0	Limited	Biomarker	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Myogenin (MYOG).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Myogenin (MYOG).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Myogenin (MYOG).	[25]

3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Myogenin (MYOG).	[21]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Myogenin (MYOG).	[22]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Myogenin (MYOG).	[23]

References

• [1] The current landscape of rhabdomyosarcomas: an update.Virchows Arch. 2020 Jan;476(1):97-108. doi: 10.1007/s00428-019-02676-9. Epub 2019 Nov 6.
• [2] RT-PCR suggests human skeletal muscle origin of alveolar soft-part sarcoma.Oncology. 2000 May;58(4):319-23. doi: 10.1159/000012119.
• [3] Mutational and Immunophenotypic Profiling of a Series of 8 Tubo-ovarian Carcinosarcomas Revealed a Monoclonal Origin of the Disease.Int J Gynecol Pathol. 2020 Jul;39(4):305-312. doi: 10.1097/PGP.0000000000000645.
• [4] Abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells from individuals with chronic fatigue syndrome.PLoS One. 2015 Apr 2;10(4):e0122982. doi: 10.1371/journal.pone.0122982. eCollection 2015.
• [5] Human bHLH transcription factor gene myogenin (MYOG): genomic sequence and negative mutation analysis in patients with severe congenital myopathies.Genomics. 1999 May 1;57(3):419-23. doi: 10.1006/geno.1998.5719.
• [6] Localization of a gene responsible for familial dilated cardiomyopathy to chromosome 1q32.Circulation. 1995 Dec 15;92(12):3387-9. doi: 10.1161/01.cir.92.12.3387.
• [7] RREB1-MKL2 fusion in biphenotypic "oropharyngeal" sarcoma: New entity or part of the spectrum of biphenotypic sinonasal sarcomas?.Genes Chromosomes Cancer. 2018 Apr;57(4):203-210. doi: 10.1002/gcc.22521. Epub 2018 Jan 25.
• [8] Aberrant neuromuscular junctions and delayed terminal muscle fiber maturation in alpha-dystroglycanopathies.Hum Mol Genet. 2006 Apr 15;15(8):1279-89. doi: 10.1093/hmg/ddl045. Epub 2006 Mar 10.
• [9] The role of AMP-activated protein kinase in the expression of the dystrophin-associated protein complex in skeletal muscle.FASEB J. 2018 Jun;32(6):2950-2965. doi: 10.1096/fj.201700868RRR. Epub 2018 Jan 11.
• [10] Overexpression of myotonic dystrophy kinase in BC3H1 cells induces the skeletal muscle phenotype.J Biol Chem. 1996 Jan 5;271(1):548-52. doi: 10.1074/jbc.271.1.548.
• [11] Clinicopathologic and Molecular Features of a Series of 41 Biphenotypic Sinonasal Sarcomas Expanding Their Molecular Spectrum.Am J Surg Pathol. 2019 Jun;43(6):747-754. doi: 10.1097/PAS.0000000000001238.
• [12] Muscle wasting in osteoarthritis model induced by anterior cruciate ligament transection.PLoS One. 2018 Apr 30;13(4):e0196682. doi: 10.1371/journal.pone.0196682. eCollection 2018.
• [13] New insights into the pathogenesis of congenital myopathies.J Child Neurol. 1994 Apr;9(2):193-201. doi: 10.1177/088307389400900218.
• [14] Histone deacetylase inhibition suppresses myogenin-dependent atrogene activation in spinal muscular atrophy mice.Hum Mol Genet. 2012 Oct 15;21(20):4448-59. doi: 10.1093/hmg/dds286. Epub 2012 Jul 13.
• [15] Identification of pathogenic genes and upstream regulators in age-related macular degeneration.BMC Ophthalmol. 2017 Jun 26;17(1):102. doi: 10.1186/s12886-017-0498-z.
• [16] Structure and promoter analysis of the human unc-33-like phosphoprotein gene. E-box required for maximal expression in neuroblastoma and myoblasts.J Biol Chem. 2000 Jun 2;275(22):16560-8. doi: 10.1074/jbc.M001312200.
• [17] Acetylcholine receptor alpha-subunit and myogenin mRNAs in thymus and thymomas.Am J Pathol. 1995 Jun;146(6):1320-4.
• [18] Satellite cell proliferation is reduced in muscles of obese Zucker rats but restored with loading.Am J Physiol Cell Physiol. 2008 Aug;295(2):C521-8. doi: 10.1152/ajpcell.00073.2008. Epub 2008 May 28.
• [19] Clusterin silencing restores myoblasts viability and down modulates the inflammatory process in osteoporotic disease.J Transl Med. 2019 Apr 10;17(1):118. doi: 10.1186/s12967-019-1868-5.
• [20] 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.
• [21] Effects of non-euphoric plant cannabinoids on muscle quality and performance of dystrophic mdx mice. Br J Pharmacol. 2019 May;176(10):1568-1584. doi: 10.1111/bph.14460. Epub 2018 Sep 9.
• [22] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [23] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [24] 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.
• [25] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.