Details of Drug Off-Target (DOT)

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

• DOT Name: Myozenin-2 (MYOZ2)
• Synonyms: Calsarcin-1; FATZ-related protein 2
• Gene Name: MYOZ2
• Related Disease:
  Adult germ cell tumor
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  Familial hypertrophic cardiomyopathy
  Germ cell tumor
  Germ cell tumour
  Non-small-cell lung cancer
  Nongerminomatous germ cell tumor
  Testicular germ cell tumor
  Arrhythmia
  Hypertrophic cardiomyopathy
  Gastric cancer
  Hypertrophic cardiomyopathy 16
  Stomach cancer
• UniProt ID: MYOZ2_HUMAN
• Pfam ID: PF05556
• Sequence:
  MLSHNTMMKQRKQQATAIMKEVHGNDVDGMDLGKKVSIPRDIMLEELSHLSNRGARLFKM
  RQRRSDKYTFENFQYQSRAQINHSIAMQNGKVDGSNLEGGSQQAPLTPPNTPDPRSPPNP
  DNIAPGYSGPLKEIPPEKFNTTAVPKYYQSPWEQAISNDPELLEALYPKLFKPEGKAELP
  DYRSFNRVATPFGGFEKASRMVKFKVPDFELLLLTDPRFMSFVNPLSGRRSFNRTPKGWI
  SENIPIVITTEPTDDTTVPESEDL
• Function: Myozenins may serve as intracellular binding proteins involved in linking Z line proteins such as alpha-actinin, gamma-filamin, TCAP/telethonin, LDB3/ZASP and localizing calcineurin signaling to the sarcomere. Plays an important role in the modulation of calcineurin signaling. May play a role in myofibrillogenesis.
• Tissue Specificity: Expressed specifically in heart and skeletal muscle.
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult germ cell tumor	DISJUCQ7	Strong	Biomarker	[1]
Dilated cardiomyopathy	DISX608J	Strong	Biomarker	[2]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[2]
Familial hypertrophic cardiomyopathy	DISQ89HN	Strong	Biomarker	[3]
Germ cell tumor	DIS62070	Strong	Biomarker	[1]
Germ cell tumour	DISOF3TK	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Nongerminomatous germ cell tumor	DISQOQJU	Strong	Biomarker	[1]
Testicular germ cell tumor	DIS5RN24	Strong	Genetic Variation	[1]
Arrhythmia	DISFF2NI	Disputed	Genetic Variation	[5]
Hypertrophic cardiomyopathy	DISQG2AI	Disputed	Autosomal dominant	[6]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[7]
Hypertrophic cardiomyopathy 16	DISWMHYX	Limited	Autosomal dominant	[8]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[7]

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 Myozenin-2 (MYOZ2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Myozenin-2 (MYOZ2).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Myozenin-2 (MYOZ2).	[11]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Myozenin-2 (MYOZ2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Myozenin-2 (MYOZ2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Myozenin-2 (MYOZ2).	[14]

References

• [1] Economy of Standards: European Association of Urology Guideline Changes Influence Treatment Costs in Stage I Testicular Cancer Patients.Urol Int. 2018;100(3):279-287. doi: 10.1159/000486343. Epub 2018 Mar 7.
• [2] MicroRNA miR-301a is a novel cardiac regulator of Cofilin-2.PLoS One. 2017 Sep 8;12(9):e0183901. doi: 10.1371/journal.pone.0183901. eCollection 2017.
• [3] Sequence analysis of myozenin 2 in 438 European patients with familial hypertrophic cardiomyopathy.Med Sci Monit. 2008 Jul;14(7):CR372-4.
• [4] Impact of Staging With Positron-emission Tomography (PET) and Comorbidities on Management and Survival of American Veterans With Stage I-III Non-Small Cell Lung Cancer.Am J Clin Oncol. 2018 May;41(5):513-518. doi: 10.1097/COC.0000000000000316.
• [5] Myozenin 2 is a novel gene for human hypertrophic cardiomyopathy. Circ Res. 2007 Mar 30;100(6):766-8. doi: 10.1161/01.RES.0000263008.66799.aa. Epub 2007 Mar 8.
• [6] 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.
• [7] Expression and prognosis of MYOZ2 in gastric cancer.Eur Rev Med Pharmacol Sci. 2018 Sep;22(18):5920-5927. doi: 10.26355/eurrev_201809_15921.
• [8] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [9] 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.
• [10] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [11] 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.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [14] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.