Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9F350W)

• DOT Name: Myosin-8 (MYH8)
• Synonyms: Myosin heavy chain 8; Myosin heavy chain, skeletal muscle, perinatal; MyHC-perinatal
• Gene Name: MYH8
• Related Disease:
  Clubfoot
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Advanced cancer
  Arthrogryposis
  Autosomal dominant prognathism
  Distal arthrogryposis
  Keloid
  Kennedy disease
  Myopathy
  Neoplasm
  Trismus-pseudocamptodactyly syndrome
  Carney complex - trismus - pseudocamptodactyly syndrome
• UniProt ID: MYH8_HUMAN
• Pfam ID: PF00063 ; PF02736 ; PF01576
• Sequence:
  MSASSDAEMAVFGEAAPYLRKSEKERIEAQNKPFDAKTSVFVAEPKESYVKSTIQSKEGG
  KVTVKTEGGATLTVREDQVFPMNPPKYDKIEDMAMMTHLHEPGVLYNLKERYAAWMIYTY
  SGLFCVTVNPYKWLPVYKPEVVAAYRGKKRQEAPPHIFSISDNAYQFMLTDRENQSILIT
  GESGAGKTVNTKRVIQYFATIAVTGEKKKDESGKMQGTLEDQIISANPLLEAFGNAKTVR
  NDNSSRFGKFIRIHFGTTGKLASADIETYLLEKSRVTFQLKAERSYHIFYQITSNKKPDL
  IEMLLITTNPYDYAFVSQGEITVPSIDDQEELMATDSAIDILGFTPEEKVSIYKLTGAVM
  HYGNMKFKQKQREEQAEPDGTEVADKAAYLQSLNSADLLKALCYPRVKVGNEYVTKGQTV
  QQVYNAVGALAKAVYEKMFLWMVTRINQQLDTKQPRQYFIGVLDIAGFEIFDFNSLEQLC
  INFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLAACIELIEKPLGIFSILEEE
  CMFPKATDTSFKNKLYDQHLGKSANFQKPKVVKGKAEAHFSLIHYAGTVDYNITGWLDKN
  KDPLNDTVVGLYQKSAMKTLASLFSTYASAEADSSAKKGAKKKGSSFQTVSALFRENLNK
  LMTNLRSTHPHFVRCIIPNETKTPGAMEHELVLHQLRCNGVLEGIRICRKGFPSRILYGD
  FKQRYKVLNASAIPEGQFIDSKKASEKLLASIDIDHTQYKFGHTKVFFKAGLLGLLEEMR
  DEKLAQIITRTQAVCRGFLMRVEYQKMLQRREALFCIQYNVRAFMNVKHWPWMKLFFKIK
  PLLKSAETEKEMATMKEEFQKTKDELAKSEAKRKELEEKMVTLLKEKNDLQLQVQSEADS
  LADAEERCEQLIKNKIQLEAKIKEVTERAEEEEEINAELTAKKRKLEDECSELKKDIDDL
  ELTLAKVEKEKHATENKVKNLTEEMAGLDETIAKLSKEKKALQETHQQTLDDLQAEEDKV
  NILTKAKTKLEQQVDDLEGSLEQEKKLRMDLERAKRKLEGDLKLAQESTMDMENDKQQLD
  EKLEKKEFEISNLISKIEDEQAVEIQLQKKIKELQARIEELGEEIEAERASRAKAEKQRS
  DLSRELEEISERLEEAGGATSAQVELNKKREAEFQKLRRDLEEATLQHEAMVAALRKKHA
  DSMAELGEQIDNLQRVKQKLEKEKSELKMETDDLSSNAEAISKAKGNLEKMCRSLEDQVS
  ELKTKEEEQQRLINDLTAQRARLQTEAGEYSRQLDEKDALVSQLSRSKQASTQQIEELKH
  QLEEETKAKNALAHALQSSRHDCDLLREQYEEEQEGKAELQRALSKANSEVAQWRTKYET
  DAIQRTEELEEAKKKLAQRLQEAEEHVEAVNAKCASLEKTKQRLQNEVEDLMLDVERSNA
  ACAALDKKQRNFDKVLSEWKQKYEETQAELEASQKESRSLSTELFKVKNVYEESLDQLET
  LRRENKNLQQEISDLTEQIAEGGKQIHELEKIKKQVEQEKCEIQAALEEAEASLEHEEGK
  ILRIQLELNQVKSEVDRKIAEKDEEIDQLKRNHTRVVETMQSTLDAEIRSRNDALRVKKK
  MEGDLNEMEIQLNHANRLAAESLRNYRNTQGILKETQLHLDDALRGQEDLKEQLAIVERR
  ANLLQAEIEELWATLEQTERSRKIAEQELLDASERVQLLHTQNTSLINTKKKLENDVSQL
  QSEVEEVIQESRNAEEKAKKAITDAAMMAEELKKEQDTSAHLERMKKNLEQTVKDLQHRL
  DEAEQLALKGGKKQIQKLEARVRELEGEVENEQKRNAEAVKGLRKHERRVKELTYQTEED
  RKNVLRLQDLVDKLQAKVKSYKRQAEEAEEQSNANLSKFRKLQHELEEAEERADIAESQV
  NKLRVKSREVHTKISAE
• Function: Muscle contraction.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway: Striated Muscle Contraction (R-HSA-390522)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clubfoot	DISLXT4S	Definitive	Biomarker	[1]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[2]
Arthrogryposis	DISC81CM	Strong	Genetic Variation	[3]
Autosomal dominant prognathism	DIS2G3FF	Strong	Altered Expression	[4]
Distal arthrogryposis	DIS3QIEL	Strong	Genetic Variation	[5]
Keloid	DISV09JY	Strong	Genetic Variation	[6]
Kennedy disease	DISXZVM1	Strong	Biomarker	[7]
Myopathy	DISOWG27	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[6]
Trismus-pseudocamptodactyly syndrome	DISZ2Y71	Strong	Autosomal dominant	[8]
Carney complex - trismus - pseudocamptodactyly syndrome	DISO70KC	Limited	Autosomal dominant	[9]

1 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 Myosin-8 (MYH8).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Myosin-8 (MYH8).	[11]

References

• [1] Variants in genes that encode muscle contractile proteins influence risk for isolated clubfoot.Am J Med Genet A. 2011 Sep;155A(9):2170-9. doi: 10.1002/ajmg.a.34167. Epub 2011 Aug 10.
• [2] Truncation of MYH8 tail in AML: a novel prognostic marker with increase cell migration and epithelial-mesenchymal transition utilizing RAF/MAPK pathway.Carcinogenesis. 2020 Jul 10;41(6):817-827. doi: 10.1093/carcin/bgz146.
• [3] Mutation of perinatal myosin heavy chain associated with a Carney complex variant.N Engl J Med. 2004 Jul 29;351(5):460-9. doi: 10.1056/NEJMoa040584.
• [4] Developmental myosin heavy chain mRNA in masseter after orthognathic surgery: a preliminary study.J Craniomaxillofac Surg. 2011 Sep;39(6):401-6. doi: 10.1016/j.jcms.2010.06.001. Epub 2010 Jul 29.
• [5] Novel deletion of lysine 7 expands the clinical, histopathological and genetic spectrum of TPM2-related myopathies.Brain. 2013 Feb;136(Pt 2):508-21. doi: 10.1093/brain/aws344.
• [6] Differential susceptible loci expression in keloid and hypertrophic scars in the Chinese Han population.Ann Plast Surg. 2015 Jan;74(1):26-9. doi: 10.1097/SAP.0000000000000364.
• [7] Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders.PLoS One. 2016 Mar 21;11(3):e0151376. doi: 10.1371/journal.pone.0151376. eCollection 2016.
• [8] Trismus-pseudocamptodactyly syndrome is caused by recurrent mutation of MYH8. Am J Med Genet A. 2006 Nov 15;140(22):2387-93. doi: 10.1002/ajmg.a.31495.
• [9] Caution in interpretation of disease causality for heterozygous loss-of-function variants in the MYH8 gene associated with autosomal dominant disorder. Eur J Med Genet. 2017 Jun;60(6):312-316. doi: 10.1016/j.ejmg.2017.03.012. Epub 2017 Apr 2.
• [10] 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.
• [11] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.