Details of Drug Off-Target (DOT)

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

• DOT Name: Myogenic factor 6 (MYF6)
• Synonyms: Myf-6; Class C basic helix-loop-helix protein 4; bHLHc4; Muscle-specific regulatory factor 4
• Gene Name: MYF6
• Related Disease:
  Becker muscular dystrophy
  Myopathy
  Cardiac failure
  Congestive heart failure
  Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4
  Rhabdomyosarcoma
  Type-1/2 diabetes
  Neoplasm
• UniProt ID: MYF6_HUMAN
• Pfam ID: PF01586 ; PF00010
• Sequence:
  MMMDLFETGSYFFYLDGENVTLQPLEVAEGSPLYPGSDGTLSPCQDQMPPEAGSDSSGEE
  HVLAPPGLQPPHCPGQCLIWACKTCKRKSAPTDRRKAATLRERRRLKKINEAFEALKRRT
  VANPNQRLPKVEILRSAISYIERLQDLLHRLDQQEKMQELGVDPFSYRPKQENLEGADFL
  RTCSSQWPSVSDHSRGLVITAKEGGASIDSSASSSLRCLSSIVDSISSEERKLPCVEEVV
  EK
• Function: Involved in muscle differentiation (myogenic factor). Induces fibroblasts to differentiate into myoblasts. Probable sequence specific DNA-binding protein.
• Tissue Specificity: Skeletal muscle.
• Reactome Pathway: Myogenesis (R-HSA-525793)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Becker muscular dystrophy	DIS5IYHL	Definitive	Biomarker	[1]
Myopathy	DISOWG27	Definitive	Genetic Variation	[1]
Cardiac failure	DISDC067	Strong	Biomarker	[2]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[2]
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4	DISGM0K5	Strong	Altered Expression	[3]
Rhabdomyosarcoma	DISNR7MS	Strong	Altered Expression	[4]
Type-1/2 diabetes	DISIUHAP	moderate	Altered Expression	[5]
Neoplasm	DISZKGEW	Limited	Altered Expression	[6]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Myogenic factor 6 (MYF6) increases the response to substance of Tretinoin.	[10]

2 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 Myogenic factor 6 (MYF6).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Myogenic factor 6 (MYF6).	[8]

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 Myogenic factor 6 (MYF6).	[9]

References

• [1] Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Becker muscular dystrophy.Neuromuscul Disord. 2000 Dec;10(8):572-7. doi: 10.1016/s0960-8966(00)00150-4.
• [2] Skeletal Muscle Resident Progenitor Cells Coexpress Mesenchymal and Myogenic Markers and Are Not Affected by Chronic Heart Failure-Induced Dysregulations.Stem Cells Int. 2019 Jan 3;2019:5690345. doi: 10.1155/2019/5690345. eCollection 2019.
• [3] 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.
• [4] Identification of a novel gene NCRMS on chromosome 12q21 with differential expression between rhabdomyosarcoma subtypes.Oncogene. 2002 May 2;21(19):3029-37. doi: 10.1038/sj.onc.1205460.
• [5] Calcineurin signaling and PGC-1alpha expression are suppressed during muscle atrophy due to diabetes.Biochim Biophys Acta. 2010 Aug;1803(8):960-7. doi: 10.1016/j.bbamcr.2010.03.019. Epub 2010 Mar 29.
• [6] Expression of members of the myf gene family in human rhabdomyosarcomas.Br J Cancer. 1991 Dec;64(6):1039-42. doi: 10.1038/bjc.1991.461.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] 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.
• [10] Response of human rhabdomyosarcoma cell lines to retinoic acid: relationship with induction of differentiation and retinoic acid sensitivity. Exp Cell Res. 2005 Dec 10;311(2):192-204. doi: 10.1016/j.yexcr.2005.09.011. Epub 2005 Oct 19.