Details of Drug Off-Target (DOT)

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

• DOT Name: Zeta-sarcoglycan (SGCZ)
• Synonyms: Zeta-SG; ZSG1
• Gene Name: SGCZ
• Related Disease:
  Acute myelogenous leukaemia
  Anxiety
  Cholelithiasis
  High blood pressure
  Myelodysplastic syndrome
  Myoclonic dystonia 11
  Panic disorder
  Rheumatoid arthritis
  Skin disease
• UniProt ID: SGCZ_HUMAN
• Pfam ID: PF04790
• Sequence:
  MTREQYILATQQNNLPRTENAQLYPVGIYGWRKRCLYFFVLLLLVTMIVNLAMTIWILKV
  MNFTVDGMGNLRVTKKGIRLEGISEFLLPLYVKEIHSRKDSPLVLQSDRNVTVNARNHMG
  QLTGQLTIGADAVEAQCKRFEVRASEDGRVLFSADEDEITIGAEKLKVTGTEGAVFGHSV
  ETPHIRAEPSQDLRLESPTRSLIMEAPRGVQVSAAAGDFKATCRKELHLQSTEGEIFLNA
  ETIKLGNLPTGSFSSSSPSSSSSRQTVYELCVCPNGKLYLSPAGVGSTCQSSSNICLWS
• 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. May play a role in the maintenance of striated muscle membrane stability.
• 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

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[1]
Anxiety	DISIJDBA	Strong	Genetic Variation	[2]
Cholelithiasis	DISERLZB	Strong	Genetic Variation	[3]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[4]
Myelodysplastic syndrome	DISYHNUI	Strong	Genetic Variation	[5]
Myoclonic dystonia 11	DISMVAWP	Strong	Genetic Variation	[5]
Panic disorder	DISD3VNY	Strong	Genetic Variation	[6]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[7]
Skin disease	DISDW8R6	Strong	Biomarker	[8]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methamphetamine	DMPM4SK	Approved	Zeta-sarcoglycan (SGCZ) affects the response to substance of Methamphetamine.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Zeta-sarcoglycan (SGCZ).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Zeta-sarcoglycan (SGCZ).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Zeta-sarcoglycan (SGCZ).	[9]

References

• [1] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [2] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [3] A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease.Nat Genet. 2007 Aug;39(8):995-9. doi: 10.1038/ng2101. Epub 2007 Jul 15.
• [4] Genome-Wide and Gene-Based Meta-Analyses Identify Novel Loci Influencing Blood Pressure Response to Hydrochlorothiazide.Hypertension. 2017 Jan;69(1):51-59. doi: 10.1161/HYPERTENSIONAHA.116.08267. Epub 2016 Oct 31.
• [5] SGCZ mutations are unlikely to be associated with myoclonus dystonia.Neuroscience. 2014 Jul 11;272:88-91. doi: 10.1016/j.neuroscience.2014.04.034. Epub 2014 Apr 30.
• [6] Genome-wide association study of panic disorder in the Japanese population.J Hum Genet. 2009 Feb;54(2):122-6. doi: 10.1038/jhg.2008.17. Epub 2009 Jan 23.
• [7] Genetic associations with radiological damage in rheumatoid arthritis: Meta-analysis of seven genome-wide association studies of 2,775 cases.PLoS One. 2019 Oct 9;14(10):e0223246. doi: 10.1371/journal.pone.0223246. eCollection 2019.
• [8] Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study.Environ Health. 2017 Jul 18;16(1):75. doi: 10.1186/s12940-017-0283-8.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [10] 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.
• [11] Genome-wide association for methamphetamine dependence: convergent results from 2 samples. Arch Gen Psychiatry. 2008 Mar;65(3):345-55. doi: 10.1001/archpsyc.65.3.345.