Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJZE032)

• DOT Name: Protein myomaker (MYMK)
• Synonyms: Myoblast fusion maker; Transmembrane protein 226; Transmembrane protein 8C
• Gene Name: MYMK
• Related Disease:
  Obsolete Carey-Fineman-Ziter syndrome
  Carey-Fineman-Ziter syndrome
  Carey-Fineman-Ziter syndrome 1
  Congenital myopathy
• UniProt ID: MYMK_HUMAN
• Pfam ID: PF12036
• Sequence:
  MGTLVAKLLLPTLSSLAFLPTVSIAAKRRFHMEAMVYLFTLFFVALHHACNGPGLSVLCF
  MRHDILEYFSVYGTALSMWVSLMALADFDEPKRSTFVMFGVLTIAVRIYHDRWGYGVYSG
  PIGTAILIIAAKWLQKMKEKKGLYPDKSVYTQQIGPGLCFGALALMLRFFFEDWDYTYVH
  SFYHCALAMSFVLLLPKVNKKAGSPGTPAKLDCSTLCCACV
• Function: Myoblast-specific protein that mediates myoblast fusion, an essential step for the formation of multi-nucleated muscle fibers. Actively participates in the membrane fusion reaction by mediating the mixing of cell membrane lipids (hemifusion) upstream of MYMX. Acts independently of MYMX. Involved in skeletal muscle regeneration in response to injury by mediating the fusion of satellite cells, a population of muscle stem cells, with injured myofibers. Also involved in skeletal muscle hypertrophy, probably by mediating the fusion of satellite cells with myofibers.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obsolete Carey-Fineman-Ziter syndrome	DISOS34F	Definitive	Autosomal recessive	[1]
Carey-Fineman-Ziter syndrome	DISURG05	Strong	Genetic Variation	[2]
Carey-Fineman-Ziter syndrome 1	DISV4HK2	Strong	Autosomal recessive	[3]
Congenital myopathy	DISLSK9G	Strong	Altered Expression	[3]

1 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 Protein myomaker (MYMK).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein myomaker (MYMK).	[5]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Knockout of myomaker results in defective myoblast fusion, reduced muscle growth and increased adipocyte infiltration in zebrafish skeletal muscle.Hum Mol Genet. 2018 Oct 15;27(20):3542-3554. doi: 10.1093/hmg/ddy268.
• [3] A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome. Nat Commun. 2017 Jul 6;8:16077. doi: 10.1038/ncomms16077.
• [4] 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.
• [5] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.