Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9F17JB)

• DOT Name: Epsilon-sarcoglycan (SGCE)
• Synonyms: Epsilon-SG
• Gene Name: SGCE
• Related Disease:
  Epilepsy
  Episodic kinesigenic dyskinesia
  Episodic kinesigenic dyskinesia 1
  Hereditary progressive chorea without dementia
  Myoclonic dystonia 11
  Alcohol dependence
  Anxiety
  Beckwith-Wiedemann syndrome
  Breast carcinoma
  Cerebellar disorder
  Cowden disease
  Depression
  Dystonia
  Dystonia 5
  Movement disorder
  Moyamoya disease
  Muscular dystrophy
  Myelodysplastic syndrome
  Osteochondritis dissecans
  Panic disorder
  Parkinsonian disorder
  Silver-Russell syndrome
  Trichohepatoenteric syndrome
  Choreatic disease
  Chromosomal disorder
  Segmental dystonia
  Tourette syndrome
  Myoclonus-dystonia syndrome
  Adult lymphoma
  Anxiety disorder
  Colorectal carcinoma
  Gastric cancer
  Lymphoma
  Mental disorder
  Obsessive compulsive disorder
  Pediatric lymphoma
  Stomach cancer
• UniProt ID: SGCE_HUMAN
• Pfam ID: PF05510 ; PF20989
• Sequence:
  MQLPRWWELGDPCAWTGQGRGTRRMSPATTGTFLLTVYSIFSKVHSDRNVYPSAGVLFVH
  VLEREYFKGEFPPYPKPGEISNDPITFNTNLMGYPDRPGWLRYIQRTPYSDGVLYGSPTA
  ENVGKPTIIEITAYNRRTFETARHNLIINIMSAEDFPLPYQAEFFIKNMNVEEMLASEVL
  GDFLGAVKNVWQPERLNAINITSALDRGGRVPLPINDLKEGVYVMVGADVPFSSCLREVE
  NPQNQLRCSQEMEPVITCDKKFRTQFYIDWCKISLVDKTKQVSTYQEVIRGEGILPDGGE
  YKPPSDSLKSRDYYTDFLITLAVPSAVALVLFLILAYIMCCRREGVEKRNMQTPDIQLVH
  HSAIQKSTKELRDMSKNREIAWPLSTLPVFHPVTGEIIPPLHTDNYDSTNMPLMQTQQNL
  PHQTQIPQQQTTGKWYP
• Function: Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Cytoskeleton in muscle cells (hsa04820)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
  Viral myocarditis (hsa05416)

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epilepsy	DISBB28L	Definitive	Genetic Variation	[1]
Episodic kinesigenic dyskinesia	DIS65CHB	Definitive	Biomarker	[2]
Episodic kinesigenic dyskinesia 1	DISGVQMP	Definitive	Biomarker	[2]
Hereditary progressive chorea without dementia	DISW33PR	Definitive	Biomarker	[2]
Myoclonic dystonia 11	DISMVAWP	Definitive	Autosomal dominant	[3]
Alcohol dependence	DIS4ZSCO	Strong	Genetic Variation	[4]
Anxiety	DISIJDBA	Strong	Genetic Variation	[4]
Beckwith-Wiedemann syndrome	DISH15GR	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[6]
Cerebellar disorder	DIS2O7WM	Strong	Biomarker	[7]
Cowden disease	DISMYKCE	Strong	Genetic Variation	[8]
Depression	DIS3XJ69	Strong	Biomarker	[9]
Dystonia	DISJLFGW	Strong	Genetic Variation	[10]
Dystonia 5	DISMPJ7S	Strong	Genetic Variation	[8]
Movement disorder	DISOJJ2D	Strong	Genetic Variation	[8]
Moyamoya disease	DISO62CA	Strong	Genetic Variation	[11]
Muscular dystrophy	DISJD6P7	Strong	Genetic Variation	[12]
Myelodysplastic syndrome	DISYHNUI	Strong	Genetic Variation	[13]
Osteochondritis dissecans	DIS1FGN4	Strong	Genetic Variation	[14]
Panic disorder	DISD3VNY	Strong	Genetic Variation	[12]
Parkinsonian disorder	DISHGY45	Strong	Altered Expression	[15]
Silver-Russell syndrome	DISSVJ1D	Strong	Biomarker	[5]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[16]
Choreatic disease	DISH8K3M	moderate	Genetic Variation	[17]
Chromosomal disorder	DISM5BB5	moderate	Genetic Variation	[18]
Segmental dystonia	DISOACMU	moderate	Biomarker	[19]
Tourette syndrome	DISX9D54	moderate	Genetic Variation	[20]
Myoclonus-dystonia syndrome	DISYK06B	Supportive	Autosomal dominant	[21]
Adult lymphoma	DISK8IZR	Limited	Altered Expression	[22]
Anxiety disorder	DISBI2BT	Limited	Genetic Variation	[4]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[23]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[24]
Lymphoma	DISN6V4S	Limited	Altered Expression	[22]
Mental disorder	DIS3J5R8	Limited	Genetic Variation	[4]
Obsessive compulsive disorder	DIS1ZMM2	Limited	Genetic Variation	[12]
Pediatric lymphoma	DIS51BK2	Limited	Altered Expression	[22]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[24]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Epsilon-sarcoglycan (SGCE) affects the response to substance of Methotrexate.	[36]
Fluorouracil	DMUM7HZ	Approved	Epsilon-sarcoglycan (SGCE) affects the response to substance of Fluorouracil.	[36]
Cyclophosphamide	DM4O2Z7	Approved	Epsilon-sarcoglycan (SGCE) affects the response to substance of Cyclophosphamide.	[36]

4 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 Epsilon-sarcoglycan (SGCE).	[25]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Epsilon-sarcoglycan (SGCE).	[29]
Triclosan	DMZUR4N	Approved	Triclosan increases the methylation of Epsilon-sarcoglycan (SGCE).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Epsilon-sarcoglycan (SGCE).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Epsilon-sarcoglycan (SGCE).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Epsilon-sarcoglycan (SGCE).	[27]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Epsilon-sarcoglycan (SGCE).	[28]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Epsilon-sarcoglycan (SGCE).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Epsilon-sarcoglycan (SGCE).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Epsilon-sarcoglycan (SGCE).	[34]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Epsilon-sarcoglycan (SGCE).	[35]

References

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• [2] Microdeletions detected using chromosome microarray in children with suspected genetic movement disorders: a single-centre study.Dev Med Child Neurol. 2012 Jul;54(7):618-23. doi: 10.1111/j.1469-8749.2012.04287.x. Epub 2012 Apr 19.
• [3] 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.
• [4] SGCE mutations cause psychiatric disorders: clinical and genetic characterization.Brain. 2013 Jan;136(Pt 1):294-303. doi: 10.1093/brain/aws308.
• [5] Quantitative analysis of methylation status at 11p15 and 7q21 for the genetic diagnosis of Beckwith-Wiedemann syndrome and Silver-Russell syndrome.J Hum Genet. 2013 Sep;58(9):604-10. doi: 10.1038/jhg.2013.67. Epub 2013 Jun 27.
• [6] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [7] Functional MRI study of response inhibition in myoclonus dystonia.Exp Neurol. 2013 Sep;247:623-9. doi: 10.1016/j.expneurol.2013.02.017. Epub 2013 Mar 6.
• [8] Myoclonus-dystonia: Distinctive motor and non-motor phenotype from other dystonia syndromes.Parkinsonism Relat Disord. 2019 Dec;69:85-90. doi: 10.1016/j.parkreldis.2019.10.015. Epub 2019 Oct 22.
• [9] Alteration of striatal dopaminergic neurotransmission in a mouse model of DYT11 myoclonus-dystonia.PLoS One. 2012;7(3):e33669. doi: 10.1371/journal.pone.0033669. Epub 2012 Mar 16.
• [10] Frameless robot-assisted pallidal deep brain stimulation surgery in pediatric patients with movement disorders: precision and short-term clinical results.J Neurosurg Pediatr. 2018 Oct;22(4):416-425. doi: 10.3171/2018.5.PEDS1814. Epub 2018 Jul 20.
• [11] Novel SGCE gene mutation in a Korean patient with myoclonus-dystonia with unique phenotype mimicking Moya-Moya disease.Mov Disord. 2007 Jun 15;22(8):1206-7. doi: 10.1002/mds.21093.
• [12] Psychiatric symptoms in myoclonus-dystonia syndrome are just concomitant features regardless of the SGCE gene mutation.Parkinsonism Relat Disord. 2017 Sep;42:73-77. doi: 10.1016/j.parkreldis.2017.06.014. Epub 2017 Jun 23.
• [13] Deep brain stimulation for myoclonus-dystonia syndrome with double mutations in DYT1 and DYT11.Sci Rep. 2017 Jan 19;7:41042. doi: 10.1038/srep41042.
• [14] Myoclonus dystonia: possible association with obsessive-compulsive disorder and alcohol dependence.Neurology. 2002 Jan 22;58(2):242-5. doi: 10.1212/wnl.58.2.242.
• [15] Genetics in dystonia.Parkinsonism Relat Disord. 2014 Jan;20 Suppl 1:S137-42. doi: 10.1016/S1353-8020(13)70033-6.
• [16] The neurophysiological features of myoclonus-dystonia and differentiation from other dystonias.JAMA Neurol. 2014 May;71(5):612-9. doi: 10.1001/jamaneurol.2014.99.
• [17] Clinical differentiation of genetically proven benign hereditary chorea and myoclonus-dystonia.Mov Disord. 2007 Oct 31;22(14):2104-9. doi: 10.1002/mds.21692.
• [18] SERT Ileu425Val in autism, Asperger syndrome and obsessive-compulsive disorder.Psychiatr Genet. 2008 Feb;18(1):31-9. doi: 10.1097/YPG.0b013e3282f08a06.
• [19] Genomic deletion size at the epsilon-sarcoglycan locus determines the clinical phenotype.Brain. 2007 Oct;130(Pt 10):2736-45. doi: 10.1093/brain/awm209.
• [20] Autosomal dominant myoclonus-dystonia and Tourette syndrome in a family without linkage to the SGCE gene.Mov Disord. 2007 Oct 31;22(14):2090-6. doi: 10.1002/mds.21674.
• [21] Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
• [22] The effects of a growth-inhibiting tripeptide, acetylGlu-Ser-GlyNH2 (Ac-ESG), on gene expression and cell cycle progression of two lymphoma cell lines.Anticancer Res. 2003 Jul-Aug;23(4):3159-65.
• [23] MMP-7 and SGCE as distinctive molecular factors in sporadic colorectal cancers from the mutator phenotype pathway.Int J Oncol. 2010 May;36(5):1209-15. doi: 10.3892/ijo_00000604.
• [24] High-definition CpG methylation of novel genes in gastric carcinogenesis identified by next-generation sequencing.Mod Pathol. 2016 Feb;29(2):182-93. doi: 10.1038/modpathol.2015.144. Epub 2016 Jan 15.
• [25] 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.
• [26] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [27] 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.
• [28] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [29] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [30] Pregnancy exposure to synthetic phenols and placental DNA methylation - An epigenome-wide association study in male infants from the EDEN cohort. Environ Pollut. 2021 Dec 1;290:118024. doi: 10.1016/j.envpol.2021.118024. Epub 2021 Aug 21.
• [31] 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.
• [32] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [33] 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.
• [34] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [35] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [36] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.