Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEFLG59)

• DOT Name: Syncoilin (SYNC)
• Synonyms: Syncoilin intermediate filament 1; Syncoilin-1
• Gene Name: SYNC
• Related Disease: Neuromuscular disease
• UniProt ID: SYNCI_HUMAN
• Pfam ID: PF00038
• Sequence:
  MASPEPRRGGDGAAQAARKTRVEANSPLPKNSGSLNEAEALNPEVTLSSEGSLNLEDILY
  LEDTGDLDETLYVQETEKAEEALYIEEAMQPDEALHVEEPGNPEETVCVEETTEPDRIQF
  VEGPVEPGKPTSPEHVVYEGETVTRAEKSNPEESLRAEQSPSMEENLSIEDLELLEGRFQ
  QCVQAVAQLEEERDQLIHELVLLREPALQEVQQVHQDILAAYKLHAQAELERDGLREEIR
  LVKQKLFKVTKECVAYQYQLECRQQDVAQFADFREVLTTRATQLSEELAQLRDAYQKQKE
  QLRQQLEAPPSQRDGHFLQESRRLSAQFENLMAESRQDLEEEYEPQFLRLLERKEAGTKA
  LQRTQAEIQEMKEALRPLQAEARQLRLQNRNLEDQIALVRQKRDEEVQQYREQLEEMEER
  QRQLRNGVQLQQQKNKEMEQLRLSLAEELSTYKAMLLPKSLEQADAPTSQAGGMETQSQG
  AV
• Function: Atypical type III intermediate filament (IF) protein that may play a supportive role in the efficient coupling of mechanical stress between the myofibril and fiber exterior. May facilitate lateral force transmission during skeletal muscle contraction. Does not form homofilaments nor heterofilaments with other IF proteins.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuromuscular disease	DISQTIJZ	Strong	Altered Expression	[1]

12 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 Syncoilin (SYNC).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Syncoilin (SYNC).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Syncoilin (SYNC).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Syncoilin (SYNC).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Syncoilin (SYNC).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Syncoilin (SYNC).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Syncoilin (SYNC).	[8]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Syncoilin (SYNC).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Syncoilin (SYNC).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Syncoilin (SYNC).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Syncoilin (SYNC).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Syncoilin (SYNC).	[12]

References

• [1] Dysbindin, syncoilin, and beta-synemin mRNA levels in dystrophic muscles.Int J Neurosci. 2010 Feb;120(2):144-9. doi: 10.3109/00207450903279717.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [12] 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.