Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNGQU7A)

• DOT Name: Rho GTPase-activating protein 26 (ARHGAP26)
• Synonyms: GTPase regulator associated with focal adhesion kinase; GRAF1; Oligophrenin-1-like protein; Rho-type GTPase-activating protein 26
• Gene Name: ARHGAP26
• Related Disease:
  Acute monocytic leukemia
  Adult acute monocytic leukemia
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Cerebellar ataxia
  Gastric cancer
  Hepatitis C virus infection
  Neoplasm
  Patent ductus arteriosus
  Psychotic disorder
  Signet ring cell carcinoma
  Stomach cancer
  Adult glioblastoma
  Coronary heart disease
  Glioblastoma multiforme
  Alpha thalassemia-X-linked intellectual disability syndrome
  Autoimmune disease
  Intellectual disability
  Retinitis pigmentosa 1
  Chronic myelomonocytic leukaemia
• UniProt ID: RHG26_HUMAN
• PDB ID: 1UGV
• Pfam ID: PF16746 ; PF00169 ; PF00620 ; PF14604
• Sequence:
  MGLPALEFSDCCLDSPHFRETLKSHEAELDKTNKFIKELIKDGKSLISALKNLSSAKRKF
  ADSLNEFKFQCIGDAETDDEMCIARSLQEFATVLRNLEDERIRMIENASEVLITPLEKFR
  KEQIGAAKEAKKKYDKETEKYCGILEKHLNLSSKKKESQLQEADSQVDLVRQHFYEVSLE
  YVFKVQEVQERKMFEFVEPLLAFLQGLFTFYHHGYELAKDFGDFKTQLTISIQNTRNRFE
  GTRSEVESLMKKMKENPLEHKTISPYTMEGYLYVQEKRHFGTSWVKHYCTYQRDSKQITM
  VPFDQKSGGKGGEDESVILKSCTRRKTDSIEKRFCFDVEAVDRPGVITMQALSEEDRRLW
  MEAMDGREPVYNSNKDSQSEGTAQLDSIGFSIIRKCIHAVETRGINEQGLYRIVGVNSRV
  QKLLSVLMDPKTASETETDICAEWEIKTITSALKTYLRMLPGPLMMYQFQRSFIKAAKLE
  NQESRVSEIHSLVHRLPEKNRQMLQLLMNHLANVANNHKQNLMTVANLGVVFGPTLLRPQ
  EETVAAIMDIKFQNIVIEILIENHEKIFNTVPDMPLTNAQLHLSRKKSSDSKPPSCSERP
  LTLFHTVQSTEKQEQRNSIINSSLESVSSNPNSILNSSSSLQPNMNSSDPDLAVVKPTRP
  NSLPPNPSPTSPLSPSWPMFSAPSSPMPTSSTSSDSSPVRSVAGFVWFSVAAVVLSLARS
  SLHAVFSLLVNFVPCHPNLHLLFDRPEEAVHEDSSTPFRKAKALYACKAEHDSELSFTAG
  TVFDNVHPSQEPGWLEGTLNGKTGLIPENYVEFL
• Function: GTPase-activating protein for RHOA and CDC42; [Isoform 2]: Associates with MICAL1 on the endosomal membrane to promote Rab8-Rab10-dependent tubule extension. After dissociation of MICAL1, recruits WDR44 which connects the endoplasmic reticulum (ER) with the endosomal tubule, thereby participating in the export of a subset of neosynthesized proteins.
• Reactome Pathway:
  RHOB GTPase cycle (R-HSA-9013026)
  RHOC GTPase cycle (R-HSA-9013106)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOD GTPase cycle (R-HSA-9013405)
  RHOQ GTPase cycle (R-HSA-9013406)
  RHOJ GTPase cycle (R-HSA-9013409)
  RAC3 GTPase cycle (R-HSA-9013423)
  RHOA GTPase cycle (R-HSA-8980692)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute monocytic leukemia	DIS28NEL	Strong	Genetic Variation	[1]
Adult acute monocytic leukemia	DISG6BLX	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[4]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[5]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Patent ductus arteriosus	DIS9P8YS	Strong	Biomarker	[8]
Psychotic disorder	DIS4UQOT	Strong	Biomarker	[9]
Signet ring cell carcinoma	DISVCUCR	Strong	Biomarker	[2]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[5]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[10]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[11]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[10]
Alpha thalassemia-X-linked intellectual disability syndrome	DISV7OEV	Limited	Altered Expression	[12]
Autoimmune disease	DISORMTM	Limited	Biomarker	[9]
Intellectual disability	DISMBNXP	Limited	Biomarker	[12]
Retinitis pigmentosa 1	DISSLQPP	Limited	Biomarker	[13]
Chronic myelomonocytic leukaemia	DISDN5P7	No Known	Unknown	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[15]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[19]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[20]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[22]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[23]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[24]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[26]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[29]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[24]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[31]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Rho GTPase-activating protein 26 (ARHGAP26).	[32]

2 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 GTPase-activating protein 26 (ARHGAP26).	[21]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Rho GTPase-activating protein 26 (ARHGAP26).	[28]

References

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