Details of Drug Off-Target (DOT)

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

DOT Name Rho GTPase-activating protein 42 (ARHGAP42)
Synonyms Rho GTPase-activating protein 10-like; Rho-type GTPase-activating protein 42
Gene Name ARHGAP42
Related Disease
Cardiovascular disease ( )
High blood pressure ( )
Advanced cancer ( )
Coronary heart disease ( )
Malignant tumor of nasopharynx ( )
Nasopharyngeal carcinoma ( )
Niemann-Pick disease type C ( )
Chronic obstructive pulmonary disease ( )
UniProt ID
RHG42_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF16746 ; PF00169 ; PF00620 ; PF14604
Sequence
MGLPTLEFSDSYLDSPDFRERLQCHEIELERTNKFIKELIKDGSLLIGALRNLSMAVQKF
SQSLQDFQFECIGDAETDDEISIAQSLKEFARLLIAVEEERRRLIQNANDVLIAPLEKFR
KEQIGAAKDGKKKFDKESEKYYSILEKHLNLSAKKKESHLQEADTQIDREHQNFYEASLE
YVFKIQEVQEKKKFEFVEPLLSFLQGLFTFYHEGYELAQEFAPYKQQLQFNLQNTRNNFE
STRQEVERLMQRMKSANQDYRPPSQWTMEGYLYVQEKRPLGFTWIKHYCTYDKGSKTFTM
SVSEMKSSGKMNGLVTSSPEMFKLKSCIRRKTDSIDKRFCFDIEVVERHGIITLQAFSEA
NRKLWLEAMDGKEPIYTLPAIISKKEEMYLNEAGFNFVRKCIQAVETRGITILGLYRIGG
VNSKVQKLMNTTFSPKSPPDIDIDIELWDNKTITSGLKNYLRCLAEPLMTYKLHKDFIIA
VKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLVKVSLHSQQNLMTVSNLGVIFGPTL
MRAQEETVAAMMNIKFQNIVVEILIEHYEKIFHTAPDPSIPLPQPQSRSGSRRTRAICLS
TGSRKPRGRYTPCLAEPDSDSYSSSPDSTPMGSIESLSSHSSEQNSTTKSASCQPREKSG
GIPWIATPSSSNGQKSLGLWTTSPESSSREDATKTDAESDCQSVASVTSPGDVSPPIDLV
KKEPYGLSGLKRASASSLRSISAAEGNKSYSGSIQSLTSVGSKETPKASPNPDLPPKMCR
RLRLDTASSNGYQRPGSVVAAKAQLFENVGSPKPVSSGRQAKAMYSCKAEHSHELSFPQG
AIFSNVYPSVEPGWLKATYEGKTGLVPENYVVFL
Function May influence blood pressure by functioning as a GTPase-activating protein for RHOA in vascular smooth muscle.
Tissue Specificity Highly and selectively expressed in smooth muscle cells.
Reactome Pathway
CDC42 GTPase cycle (R-HSA-9013148 )
RAC1 GTPase cycle (R-HSA-9013149 )
RAC2 GTPase cycle (R-HSA-9013404 )
RAC3 GTPase cycle (R-HSA-9013423 )
RHOA GTPase cycle (R-HSA-8980692 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cardiovascular disease DIS2IQDX Strong Genetic Variation [1]
High blood pressure DISY2OHH Strong Biomarker [2]
Advanced cancer DISAT1Z9 moderate Altered Expression [3]
Coronary heart disease DIS5OIP1 moderate Genetic Variation [4]
Malignant tumor of nasopharynx DISTGIGF moderate Altered Expression [3]
Nasopharyngeal carcinoma DISAOTQ0 moderate Altered Expression [3]
Niemann-Pick disease type C DIS492ZO moderate Altered Expression [3]
Chronic obstructive pulmonary disease DISQCIRF Limited Genetic Variation [5]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Rho GTPase-activating protein 42 (ARHGAP42). [6]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Rho GTPase-activating protein 42 (ARHGAP42). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Rho GTPase-activating protein 42 (ARHGAP42). [14]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Rho GTPase-activating protein 42 (ARHGAP42). [9]
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8 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 Rho GTPase-activating protein 42 (ARHGAP42). [7]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Rho GTPase-activating protein 42 (ARHGAP42). [8]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Rho GTPase-activating protein 42 (ARHGAP42). [10]
Melphalan DMOLNHF Approved Melphalan decreases the expression of Rho GTPase-activating protein 42 (ARHGAP42). [11]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Rho GTPase-activating protein 42 (ARHGAP42). [12]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Rho GTPase-activating protein 42 (ARHGAP42). [13]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Rho GTPase-activating protein 42 (ARHGAP42). [15]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Rho GTPase-activating protein 42 (ARHGAP42). [16]
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⏷ Show the Full List of 8 Drug(s)

References

1 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
2 Haploinsufficiency of ARHGAP42 is associated with hypertension.Eur J Hum Genet. 2019 Aug;27(8):1296-1303. doi: 10.1038/s41431-019-0382-9. Epub 2019 Mar 21.
3 ARHGAP42 promotes cell migration and invasion involving PI3K/Akt signaling pathway in nasopharyngeal carcinoma.Cancer Med. 2018 Aug;7(8):3862-3874. doi: 10.1002/cam4.1552. Epub 2018 Jun 24.
4 Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
5 Genetic overlap of chronic obstructive pulmonary disease and cardiovascular disease-related traits: a large-scale genome-wide cross-trait analysis.Respir Res. 2019 Apr 2;20(1):64. doi: 10.1186/s12931-019-1036-8.
6 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.
7 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
8 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.
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 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
11 Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
12 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
13 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
14 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.
15 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
16 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.