Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9BPJCL)

• DOT Name: Rho guanine nucleotide exchange factor 7 (ARHGEF7)
• Synonyms: Beta-Pix; COOL-1; PAK-interacting exchange factor beta; p85
• Gene Name: ARHGEF7
• Related Disease:
  Neuroblastoma
  Adenocarcinoma
  Advanced cancer
  Alzheimer disease
  Astrocytoma
  B-cell neoplasm
  Breast neoplasm
  Classic Hodgkin lymphoma
  Colon cancer
  Colon carcinoma
  Endometrial carcinoma
  Glioblastoma multiforme
  Glioma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Melanoma
  Neoplasm
  Non-small-cell lung cancer
  OPTN-related open angle glaucoma
  Osteoarthritis
  Pancreatic cancer
  Polycythemia
  Primary familial polycythemia due to EPO receptor mutation
  Prostate cancer
  Prostate carcinoma
  Psychotic disorder
  Small lymphocytic lymphoma
  Type-1/2 diabetes
  Adult glioblastoma
  Amyotrophic lateral sclerosis
  Breast cancer
  Breast carcinoma
  Clear cell renal carcinoma
  Epithelial ovarian cancer
  Ovarian cancer
  Thyroid gland carcinoma
  Acute myelogenous leukaemia
  Bipolar disorder
  Cognitive impairment
  Colorectal carcinoma
  Coronary heart disease
  Hepatitis C virus infection
  Mental disorder
  Metastatic malignant neoplasm
  Nasopharyngeal carcinoma
  Rheumatoid arthritis
• UniProt ID: ARHG7_HUMAN
• PDB ID: 1BY1; 1ZSG; 2L3G; 5SXP
• Pfam ID: PF00307 ; PF00169 ; PF00621 ; PF16615 ; PF16614 ; PF07653
• Sequence:
  MNSAEQTVTWLITLGVLESPKKTISDPEGFLQASLKDGVVLCRLLERLLPGTIEKVYPEP
  RSESECLSNIREFLRGCGASLRLELLFPPSQPPQHLVTTILLSASTFDANDLYQGQNFNK
  VLSSLVTLNKVTADIGLGSDSVCARPSSHRIKSFDSLGSQSLHTRTSKLFQGQYRSLDMT
  DNSNNQLVVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE
  VKASEKPVSPKSGTLKSPPKGFDTTAINKSYYNVVLQNILETENEYSKELQTVLSTYLRP
  LQTSEKLSSANISYLMGNLEEICSFQQMLVQSLEECTKLPEAQQRVGGCFLNLMPQMKTL
  YLTYCANHPSAVNVLTEHSEELGEFMETKGASSPGILVLTTGLSKPFMRLDKYPTLLKEL
  ERHMEDYHTDRQDIQKSMAAFKNLSAQCQEVRKRKELELQILTEAIRNWEGDDIKTLGNV
  TYMSQVLIQCAGSEEKNERYLLLFPNVLLMLSASPRMSGFIYQGKLPTTGMTITKLEDSE
  NHRNAFEISGSMIERILVSCNNQQDLQEWVEHLQKQTKVTSVGNPTIKPHSVPSHTLPSH
  PVTPSSKHADSKPAPLTPAYHTLPHPSHHGTPHTTINWGPLEPPKTPKPWSLSCLRPAPP
  LRPSAALCYKEDLSKSPKTMKKLLPKRKPERKPSDEEFASRKSTAALEEDAQILKVIEAY
  CTSAKTRQTLNSTWQGTDLMHNHVLADDDQPSLDSLGRRSSLSRLEPSDLSEDSDYDSIW
  TAHSYRMGSTSRKSCCSYISHQN
• Function: Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. Functions in cell migration, attachment and cell spreading. Promotes targeting of RAC1 to focal adhesions. May function as a positive regulator of apoptosis. Downstream of NMDA receptors and CaMKK-CaMK1 signaling cascade, promotes the formation of spines and synapses in hippocampal neurons.
• KEGG Pathway:
  Regulation of actin cytoskeleton (hsa04810)
  Yersinia infection (hsa05135)
• Reactome Pathway:
  (Name not found)
  NRAGE signals death through JNK (R-HSA-193648)
  Ephrin signaling (R-HSA-3928664)
  G alpha (12/13) signalling events (R-HSA-416482)
  RHOA GTPase cycle (R-HSA-8980692)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RHOQ GTPase cycle (R-HSA-9013406)
  RHOJ GTPase cycle (R-HSA-9013409)
  RHOU GTPase cycle (R-HSA-9013420)
  RHOV GTPase cycle (R-HSA-9013424)
  EGFR downregulation (R-HSA-182971)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	Definitive	Altered Expression	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Astrocytoma	DISL3V18	Strong	Altered Expression	[5]
B-cell neoplasm	DISVY326	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[7]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[8]
Colon cancer	DISVC52G	Strong	Biomarker	[9]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[9]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[10]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[11]
Glioma	DIS5RPEH	Strong	Biomarker	[12]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[13]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Melanoma	DIS1RRCY	Strong	Altered Expression	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[16]
OPTN-related open angle glaucoma	DISDR98A	Strong	Biomarker	[17]
Osteoarthritis	DIS05URM	Strong	Biomarker	[18]
Pancreatic cancer	DISJC981	Strong	Biomarker	[19]
Polycythemia	DIS8B6VW	Strong	Genetic Variation	[20]
Primary familial polycythemia due to EPO receptor mutation	DISFVI97	Strong	Biomarker	[21]
Prostate cancer	DISF190Y	Strong	Altered Expression	[22]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[22]
Psychotic disorder	DIS4UQOT	Strong	Biomarker	[23]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[24]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[25]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[12]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[26]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[27]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[27]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[28]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[29]
Ovarian cancer	DISZJHAP	moderate	Biomarker	[29]
Thyroid gland carcinoma	DISMNGZ0	moderate	Altered Expression	[30]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[31]
Bipolar disorder	DISAM7J2	Limited	Genetic Variation	[32]
Cognitive impairment	DISH2ERD	Limited	Biomarker	[33]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[34]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[35]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[36]
Mental disorder	DIS3J5R8	Limited	Biomarker	[37]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[38]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[39]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[41]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[42]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[43]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[44]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[45]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[47]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[48]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[49]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[50]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[51]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[49]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[52]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[53]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[56]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Rho guanine nucleotide exchange factor 7 (ARHGEF7).	[55]

References

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