Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCB2IJB)

• DOT Name: Myosin-7B (MYH7B)
• Synonyms: Antigen MLAA-21; Myosin cardiac muscle beta chain; Myosin heavy chain 7B, cardiac muscle beta isoform; Slow A MYH14
• Gene Name: MYH7B
• Related Disease:
  Cardiomyopathy
  Colorectal carcinoma
  Congenital fiber-type disproportion myopathy
  Congenital myopathy
  Melanoma
  Left ventricular noncompaction
  Cutaneous melanoma
  Dilated cardiomyopathy
  Hypoplastic left heart syndrome 1
• UniProt ID: MYH7B_HUMAN
• Pfam ID: PF00063 ; PF02736 ; PF01576
• Sequence:
  MSGNKRGSRASCPHRGAECLLPWAALNLQGFQLLLLHPSATAMMDVSELGESARYLRQGY
  QEMTKVHTIPWDGKKRVWVPDEQDAYVEAEVKSEATGGRVTVETKDQKVLMVREAELQPM
  NPPRFDLLEDMAMMTHLNEASVLHNLRQRYARWMIYTYSGLFCVTINPYKWLPVYTASVV
  AAYKGKRRSDSPPHIYAVADNAYNDMLRNRDNQSMLITGESGAGKTVNTKRVIQYFAIVA
  ALGDGPGKKAQFLATKTGGTLEDQIIEANPAMEAFGNAKTLRNDNSSRFGKFIRIHFGPS
  GKLASADIDSYLLEKSRVIFQLPGERSYHVYYQILSGRKPELQDMLLLSMNPYDYHFCSQ
  GVITVDNMNDGEELIATDHAMDILGFSVDEKCACYKIVGALLHFGNMKFKQKQREEQAEA
  DGTESADKAAYLMGVSSGDLLKGLLHPRVRVGNEYVTKGQSVEQVVFAVGALAKATYDRL
  FRWLVSRINQTLDTKLPRQFFIGVLDIAGFEIFEFNSFEQLCINFTNEKLQQFFNQHMFV
  LEQEEYKREGIDWVFIDFGLDLQPCIDLIEKPLGILSILEEECMFPKASDASFRAKLYDN
  HAGKSPNFQQPRPDKKRKYQAHFEVVHYAGVVPYSIVGWLEKNKDPLNETVVPIFQKSQN
  RLLATLYENYAGSCSTEPPKSGVKEKRKKAASFQTVSQLHKENLNKLMTNLRATQPHFVR
  CIVPNENKTPGVMDAFLVLHQLRCNGVLEGIRICRQGFPNRLLYTDFRQRYRILNPSAIP
  DDTFMDSRKATEKLLGSLDLDHTQYQFGHTKVFFKAGLLGVLEELRDQRLAKVLTLLQAR
  SRGRLMRLEYQRLLGGRDALFTIQWNIRAFNAVKNWSWMKLFFKMKPLLRSAQAEEELAA
  LRAELRGLRGALAAAEAKRQELEETHVSITQEKNDLALQLQAEQDNLADAEERCHLLIKS
  KVQLEGKVKELSERLEDEEEVNADLAARRRKLEDECTELKKDIDDLELTLAKAEKEKQAT
  ENKVKNLTEEMAALDESVARLTKEKKALQEAHQQALGDLQAEEDRVSALTKAKLRLEQQV
  EDLECSLEQEKKLRMDTERAKRKLEGDLKLTQESVADAAQDKQQLEEKLKKKDSELSQLS
  LRVEDEQLLGAQMQKKIKELQARAEELEEELEAERAARARVEKQRAEAARELEELSERLE
  EAGGASAGQREGCRKREAELGRLRRELEEAALRHEATVAALRRKQAEGAAELGEQVDSLQ
  RVRQKLEKEKSELRMEVDDLAANVETLTRAKASAEKLCRTYEDQLSEAKIKVEELQRQLA
  DASTQRGRLQTESGELSRLLEEKECLISQLSRGKALAAQSLEELRRQLEEESKAKSALAH
  AVQALRHDCDLLREQHEEEAEAQAELQRLLSKANAEVAQWRSKYEADAIQRTEELEEAKK
  KLALRLQEAEEGVEAANAKCSSLEKAKLRLQTESEDVTLELERATSAAAALDKKQRHLER
  ALEERRRQEEEMQRELEAAQRESRGLGTELFRLRHGHEEALEALETLKRENKNLQEEISD
  LTDQVSLSGKSIQELEKTKKALEGEKSEIQAALEEAEGALELEETKTLRIQLELSQVKAE
  VDRKLAEKDEECANLRRNHQRAVESLQASLDAETRARNEALRLKKKMEGDLNDLELQLGH
  ATRQATEAQAATRLMQAQLKEEQAGRDEEQRLAAELHEQAQALERRASLLAAELEELRAA
  LEQGERSRRLAEQELLEATERLNLLHSQNTGLLNQKKKLEADLAQLSGEVEEAAQERREA
  EEKAKKAITDAAMMAEELKKEQDTSAHLERMKKTLEQTVRELQARLEEAEQAALRGGKKQ
  VQKLEAKVRELEAELDAEQKKHAEALKGVRKHERRVKELAYQAEEDRKNLARMQDLVDKL
  QSKVKSYKRQFEEAEQQANTNLAKYRKAQHELDDAEERADMAETQANKLRARTRDALGPK
  HKE
• Function: Involved in muscle contraction.
• Tissue Specificity: Expressed in heart, skeletal muscle, testis, and all specific brain regions examined. Slightly lower expression was detected in ovary and kidney, and intermediate expression was detected in lung, pancreas, spleen and liver.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Cytoskeleton in muscle cells (hsa04820)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiomyopathy	DISUPZRG	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Congenital fiber-type disproportion myopathy	DISU9T2M	Strong	Genetic Variation	[3]
Congenital myopathy	DISLSK9G	Strong	Genetic Variation	[3]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[4]
Left ventricular noncompaction	DISJ4QEG	Supportive	Autosomal dominant	[3]
Cutaneous melanoma	DIS3MMH9	Limited	Genetic Variation	[5]
Dilated cardiomyopathy	DISX608J	Limited	Altered Expression	[1]
Hypoplastic left heart syndrome 1	DISW3OY8	Limited	Genetic Variation	[6]

2 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 Myosin-7B (MYH7B).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Myosin-7B (MYH7B).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Myosin-7B (MYH7B).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Myosin-7B (MYH7B).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Myosin-7B (MYH7B).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Myosin-7B (MYH7B).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Myosin-7B (MYH7B).	[13]

References

• [1] Expression of Normally Repressed Myosin Heavy Chain 7b in the Mammalian Heart Induces Dilated Cardiomyopathy.J Am Heart Assoc. 2019 Aug 6;8(15):e013318. doi: 10.1161/JAHA.119.013318. Epub 2019 Jul 31.
• [2] Recurrent, low-frequency coding variants contributing to colorectal cancer in the Swedish population.PLoS One. 2018 Mar 16;13(3):e0193547. doi: 10.1371/journal.pone.0193547. eCollection 2018.
• [3] Digenic mutational inheritance of the integrin alpha 7 and the myosin heavy chain 7B genes causes congenital myopathy with left ventricular non-compact cardiomyopathy. Orphanet J Rare Dis. 2013 Jun 21;8:91. doi: 10.1186/1750-1172-8-91.
• [4] Two-stage genome-wide association study identifies a novel susceptibility locus associated with melanoma.Oncotarget. 2017 Mar 14;8(11):17586-17592. doi: 10.18632/oncotarget.15230.
• [5] Comprehensive field synopsis and systematic meta-analyses of genetic association studies in cutaneous melanoma.J Natl Cancer Inst. 2011 Aug 17;103(16):1227-35. doi: 10.1093/jnci/djr219. Epub 2011 Jun 21.
• [6] A genome-wide association study of congenital cardiovascular left-sided lesions shows association with a locus on chromosome 20.Hum Mol Genet. 2016 Jun 1;25(11):2331-2341. doi: 10.1093/hmg/ddw071. Epub 2016 Mar 9.
• [7] 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.
• [8] 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.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [12] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [13] Low doses of BPA induced abnormal mitochondrial fission and hypertrophy in human embryonic stem cell-derived cardiomyocytes via the calcineurin-DRP1 signaling pathway: A comparison between XX and XY cardiomyocytes. Toxicol Appl Pharmacol. 2020 Feb 1;388:114850. doi: 10.1016/j.taap.2019.114850. Epub 2019 Dec 9.