Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT61R1HP)

• DOT Name: Myoneurin (MYNN)
• Synonyms: Zinc finger and BTB domain-containing protein 31
• Gene Name: MYNN
• Related Disease:
  Bladder cancer
  Coeliac disease
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Multiple sclerosis
  Plasma cell myeloma
  Urinary bladder cancer
  Small lymphocytic lymphoma
  Urinary bladder neoplasm
• UniProt ID: MYNN_HUMAN
• PDB ID: 2VPK
• Pfam ID: PF00651 ; PF00096 ; PF13912
• Sequence:
  MQYSHHCEHLLERLNKQREAGFLCDCTIVIGEFQFKAHRNVLASFSEYFGAIYRSTSENN
  VFLDQSQVKADGFQKLLEFIYTGTLNLDSWNVKEIHQAADYLKVEEVVTKCKIKMEDFAF
  IANPSSTEISSITGNIELNQQTCLLTLRDYNNREKSEVSTDLIQANPKQGALAKKSSQTK
  KKKKAFNSPKTGQNKTVQYPSDILENASVELFLDANKLPTPVVEQVAQINDNSELELTSV
  VENTFPAQDIVHTVTVKRKRGKSQPNCALKEHSMSNIASVKSPYEAENSGEELDQRYSKA
  KPMCNTCGKVFSEASSLRRHMRIHKGVKPYVCHLCGKAFTQCNQLKTHVRTHTGEKPYKC
  ELCDKGFAQKCQLVFHSRMHHGEEKPYKCDVCNLQFATSSNLKIHARKHSGEKPYVCDRC
  GQRFAQASTLTYHVRRHTGEKPYVCDTCGKAFAVSSSLITHSRKHTGEKPYICGICGKSF
  ISSGELNKHFRSHTGERPFICELCGNSYTDIKNLKKHKTKVHSGADKTLDSSAEDHTLSE
  QDSIQKSPLSETMDVKPSDMTLPLALPLGTEDHHMLLPVTDTQSPTSDTLLRSTVNGYSE
  PQLIFLQQLY
• Tissue Specificity: Mainly expressed in the neuromuscular system. Located in and around synaptic myonuclei in adult muscle. Expression is dysregulated after nerve injury. Also found in the testis, ovary and placenta.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[1]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[2]
Colon cancer	DISVC52G	Strong	Genetic Variation	[3]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[3]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[3]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[3]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[3]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[3]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[3]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[4]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[5]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[1]
Small lymphocytic lymphoma	DIS30POX	Disputed	Genetic Variation	[6]
Urinary bladder neoplasm	DIS7HACE	Limited	Genetic Variation	[1]

11 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 Myoneurin (MYNN).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Myoneurin (MYNN).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Myoneurin (MYNN).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Myoneurin (MYNN).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Myoneurin (MYNN).	[10]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Myoneurin (MYNN).	[11]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Myoneurin (MYNN).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Myoneurin (MYNN).	[14]
Celastrol	DMWQIJX	Preclinical	Celastrol decreases the expression of Myoneurin (MYNN).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Myoneurin (MYNN).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Myoneurin (MYNN).	[17]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Myoneurin (MYNN).	[13]

References

• [1] The Association of MYNN and TERC Gene Polymorphisms and Bladder Cancer in a Turkish Population.Urol J. 2019 Feb 21;16(1):50-55. doi: 10.22037/uj.v0i0.4083.
• [2] Multiple common variants for celiac disease influencing immune gene expression.Nat Genet. 2010 Apr;42(4):295-302. doi: 10.1038/ng.543. Epub 2010 Feb 28.
• [3] Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33.Nat Genet. 2010 Nov;42(11):973-7. doi: 10.1038/ng.670. Epub 2010 Oct 24.
• [4] Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.Nature. 2011 Aug 10;476(7359):214-9. doi: 10.1038/nature10251.
• [5] Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk.Nat Genet. 2013 Oct;45(10):1221-1225. doi: 10.1038/ng.2733. Epub 2013 Aug 18.
• [6] A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.Nat Genet. 2014 Jan;46(1):56-60. doi: 10.1038/ng.2843. Epub 2013 Dec 1.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [14] 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.
• [15] Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
• [16] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.