Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5R5LAT)

• DOT Name: Beta-sarcoglycan (SGCB)
• Synonyms: Beta-SG; 43 kDa dystrophin-associated glycoprotein; 43DAG; A3b
• Gene Name: SGCB
• Related Disease:
  Autosomal recessive limb-girdle muscular dystrophy
  Autosomal recessive limb-girdle muscular dystrophy type 2E
• UniProt ID: SGCB_HUMAN
• Pfam ID: PF04790
• Sequence:
  MAAAAAAAAEQQSSNGPVKKSMREKAVERRSVNKEHNSNFKAGYIPIDEDRLHKTGLRGR
  KGNLAICVIILLFILAVINLIITLVIWAVIRIGPNGCDSMEFHESGLLRFKQVSDMGVIH
  PLYKSTVGGRRNENLVITGNNQPIVFQQGTTKLSVENNKTSITSDIGMQFFDPRTQNILF
  STDYETHEFHLPSGVKSLNVQKASTERITSNATSDLNIKVDGRAIVRGNEGVFIMGKTIE
  FHMGGNMELKAENSIILNGSVMVSTTRLPSSSSGDQLGSGDWVRYKLCMCADGTLFKVQV
  TSQNMGCQISDNPCGNTH
• 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: Highest expression in heart and skeletal muscle. Low expression in brain, kidney, placenta, pancreas and lung. High expression in fetal brain. Also found in fetal lung, kidney and liver.
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive limb-girdle muscular dystrophy	DISWPGLM	Definitive	Autosomal recessive	[1]
Autosomal recessive limb-girdle muscular dystrophy type 2E	DISQH5PB	Definitive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Beta-sarcoglycan (SGCB) affects the response to substance of Paclitaxel.	[10]

8 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 Beta-sarcoglycan (SGCB).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Beta-sarcoglycan (SGCB).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Beta-sarcoglycan (SGCB).	[4]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Beta-sarcoglycan (SGCB).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Beta-sarcoglycan (SGCB).	[6]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Beta-sarcoglycan (SGCB).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Beta-sarcoglycan (SGCB).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Beta-sarcoglycan (SGCB).	[9]

References

• [1] 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.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Effect of all-trans retinoic acid on sodium/iodide symporter expression, radioiodine uptake and gene expression profiles in a human anaplastic thyroid carcinoma cell line. Nucl Med Biol. 2006 Oct;33(7):875-82. doi: 10.1016/j.nucmedbio.2006.07.004.
• [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] Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. Pharmacogenomics J. 2003;3(1):27-40.
• [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] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [8] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [9] 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.
• [10] 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.