Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG1STV8)

• DOT Name: Rho GTPase-activating protein 20 (ARHGAP20)
• Synonyms: Rho-type GTPase-activating protein 20
• Gene Name: ARHGAP20
• Related Disease:
  Alzheimer disease
  Small lymphocytic lymphoma
• UniProt ID: RHG20_HUMAN
• PDB ID: 3MSX
• Pfam ID: PF00788 ; PF00620
• Sequence:
  MEAMSPQQETLGGQPGRSSSLTGVSRLAGGSCTKKKMKTLAERRRSAPSLILDKALQKRP
  TTRDSPSASVDTCTFLSSLVCSNRTLLIDGRAELKRGLQRQERHLFLFNDLFVVAKIKYN
  NNFKIKNKIKLTDMWTASCVDEVGEGNTNAMKSFVLGWPTVNFVATFSSPEQKDKWLSLL
  QRYINLEKEKDYPKSIPLKIFAKDIGNCAYSKTITVMNSDTANEVINMSLPMLGITGSER
  DYQLWVNSGKEEAPYPLIGHEYPYGIKMSHLRDSALLTPGSKDSTTPFNLQEPFLMEQLP
  REMQCQFILKPSRLAAAQQLSDSGHKTFKRRRSIINWAFWRGSSTHLDNLPSSPTSPMPG
  QLFGISLPNICENDNLPKPVLDMLFFLNQKGPLTKGIFRQSANVKSCRELKEKLNSGVEV
  HLDCESIFVIASVLKDFLRNIPGSIFSSDLYDHWVSVMDQGNDEEKINTVQRLLDQLPRA
  NVVLLRYLFGVLHNIEQHSSSNQMTAFNLAVCVAPSILWPPASSSPELENEFTKKVSLLI
  QFLIENCLRIFGEEITSLFREVSVRCDTRENASDISCFQLNDSSYDSLENELNEDVDAPC
  SDLVKKLGQGSRSMDSVLTLSDYDLDQPEVEGLLTLSDFDLAHSKDEDVQMKRPLESKPV
  NILVYTKIPLRDHARAPSAMCTPSYLSTAAANAAKSLRRHRRCSEPSIDYLDSKLSYLRE
  FYQKKLRKSSCDAILSQKDEDYLKQNQPLQEEGKTCFKQSLVTGTDVSKKNATTQNTKKK
  SLSGSEGNHVKLFPKSKPVAISVASYSPMSSQDHSKNQPFDVNTSGYSPPHTADALKGPR
  THRRCSEPNIEDQNRKLTYLRGIYSKKQHKTSCEAGLLHGEEDYLKRHKSLQMEGQKLIN
  QSLVMGIEVGKSSATNQNTEKVLPPRLNLCPRTSYSSLSSPGTSPSGSSVSSQDSAFSQI
  SEHSVFTPTETSSPIDCTFQAQRKREDLSPDFSNASHVSGMPGPSSGQACSRPAYTKKDT
  MEWHSQMHSVTLHPSTWLRNGVASLKNWSLKKKAKAARPEEEKIASPKGPLEPPPHASGV
  PEANSLQEEQKDLPLRAAEGLSPVQSAQRCSSSPFQDSERHCSSPFSLVESRLKLCMKSH
  EEIEPGSQSSSGSLPWERASASSWTLEDATSPDSGPTVVCDIEDRYLTKDI
• Function: GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.
• Tissue Specificity: Expressed predominantly in the brain. Lower expression is found in lymph nodes.
• Reactome Pathway:
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RHOA GTPase cycle (R-HSA-8980692)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Rho GTPase-activating protein 20 (ARHGAP20).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Rho GTPase-activating protein 20 (ARHGAP20).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Rho GTPase-activating protein 20 (ARHGAP20).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Rho GTPase-activating protein 20 (ARHGAP20).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Rho GTPase-activating protein 20 (ARHGAP20).	[8]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Rho GTPase-activating protein 20 (ARHGAP20).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Rho GTPase-activating protein 20 (ARHGAP20).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Rho GTPase-activating protein 20 (ARHGAP20).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Rho GTPase-activating protein 20 (ARHGAP20).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Rho GTPase-activating protein 20 (ARHGAP20).	[7]

References

• [1] Genome-wide association study of the rate of cognitive decline in Alzheimer's disease.Alzheimers Dement. 2014 Jan;10(1):45-52. doi: 10.1016/j.jalz.2013.01.008. Epub 2013 Mar 25.
• [2] Expression analysis of genes located in the minimally deleted regions of 13q14 and 11q22-23 in chronic lymphocytic leukemia-unexpected expression pattern of the RHO GTPase activator ARHGAP20.Genes Chromosomes Cancer. 2011 Jul;50(7):546-58. doi: 10.1002/gcc.20879. Epub 2011 Apr 15.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] 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.
• [8] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [9] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [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] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.