Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPA3F8Q)

• DOT Name: Rho-related GTP-binding protein RhoF (RHOF)
• Synonyms: Rho family GTPase Rif; Rho in filopodia
• Gene Name: RHOF
• Related Disease:
  Coagulation defect
  Disseminated intravascular coagulation
  Drug-resistant tuberculosis
  Endometriosis
  Eosinophilic esophagitis
  Esophageal squamous cell carcinoma
  Hepatitis
  Hepatitis A virus infection
  Hydrocephalus
  Inflammation
  Melioidosis
  Meningeal tuberculosis
  Multi-drug resistant tuberculosis
  Mycosis fungoides
  Neoplasm
  Pancreatic cancer
  Pleural tuberculosis
  Promyelocytic leukaemia
  Thrombocytopenia
  Follicular lymphoma
  Lymphoma
  Malaria
  Methicillin-resistant staphylococci infection
  Osteomyelitis
• UniProt ID: RHOF_HUMAN
• Pfam ID: PF00071
• Sequence:
  MDAPGALAQTAAPGPGRKELKIVIVGDGGCGKTSLLMVYSQGSFPEHYAPSVFEKYTASV
  TVGSKEVTLNLYDTAGQEDYDRLRPLSYQNTHLVLICYDVMNPTSYDNVLIKWFPEVTHF
  CRGIPMVLIGCKTDLRKDKEQLRKLRAAQLEPITYMQGLSACEQIRAALYLECSAKFREN
  VEDVFREAAKVALSALKKAQRQKKRRLCLLL
• Function: Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. Causes the formation of thin, actin-rich surface projections called filopodia. Functions cooperatively with CDC42 and Rac to generate additional structures, increasing the diversity of actin-based morphology.
• Reactome Pathway:
  RHOF GTPase cycle (R-HSA-9035034)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coagulation defect	DIS9X3H6	Strong	Biomarker	[1]
Disseminated intravascular coagulation	DISCAVOZ	Strong	Biomarker	[1]
Drug-resistant tuberculosis	DIS5BUFB	Strong	Biomarker	[2]
Endometriosis	DISX1AG8	Strong	Biomarker	[3]
Eosinophilic esophagitis	DISR8WSB	Strong	Altered Expression	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[4]
Hepatitis	DISXXX35	Strong	Biomarker	[5]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[5]
Hydrocephalus	DISIZUF7	Strong	Biomarker	[6]
Inflammation	DISJUQ5T	Strong	Altered Expression	[4]
Melioidosis	DISB13HR	Strong	Biomarker	[7]
Meningeal tuberculosis	DIS8KHDE	Strong	Biomarker	[8]
Multi-drug resistant tuberculosis	DIS1A2CS	Strong	Biomarker	[9]
Mycosis fungoides	DIS62RB8	Strong	Genetic Variation	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[11]
Pleural tuberculosis	DISD09EG	Strong	Biomarker	[8]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[1]
Thrombocytopenia	DISU61YW	Strong	Biomarker	[1]
Follicular lymphoma	DISVEUR6	Limited	Altered Expression	[12]
Lymphoma	DISN6V4S	Limited	Altered Expression	[12]
Malaria	DISQ9Y50	Limited	Biomarker	[13]
Methicillin-resistant staphylococci infection	DIS6DRDZ	Limited	Genetic Variation	[14]
Osteomyelitis	DIS0VUZL	Limited	Biomarker	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Rho-related GTP-binding protein RhoF (RHOF) decreases the response to substance of Arsenic trioxide.	[26]

10 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-related GTP-binding protein RhoF (RHOF).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Rho-related GTP-binding protein RhoF (RHOF).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Rho-related GTP-binding protein RhoF (RHOF).	[18]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Rho-related GTP-binding protein RhoF (RHOF).	[19]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Rho-related GTP-binding protein RhoF (RHOF).	[20]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Rho-related GTP-binding protein RhoF (RHOF).	[21]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Rho-related GTP-binding protein RhoF (RHOF).	[22]
Adenosine triphosphate	DM79F6G	Approved	Adenosine triphosphate increases the expression of Rho-related GTP-binding protein RhoF (RHOF).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Rho-related GTP-binding protein RhoF (RHOF).	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Rho-related GTP-binding protein RhoF (RHOF).	[25]

References

• [1] The impact of oral arsenic and all-trans-retinoic acid on coagulopathy in acute promyelocytic leukemia.Leuk Res. 2018 Feb;65:14-19. doi: 10.1016/j.leukres.2017.11.009. Epub 2017 Nov 15.
• [2] Abbott RealTime MTB and MTB RIF/INH assays for the diagnosis of tuberculosis and rifampicin/isoniazid resistance.Infect Genet Evol. 2019 Jul;71:54-59. doi: 10.1016/j.meegid.2019.03.012. Epub 2019 Mar 20.
• [3] Preliminary functional inquiry of lncRNA ENST00000433673 in embryo implantation using bioinformatics analysis.Syst Biol Reprod Med. 2019 Apr;65(2):164-173. doi: 10.1080/19396368.2018.1563844. Epub 2019 Jan 16.
• [4] KLF4 activates NFB signaling and esophageal epithelial inflammation via the Rho-related GTP-binding protein RHOF.PLoS One. 2019 Apr 18;14(4):e0215746. doi: 10.1371/journal.pone.0215746. eCollection 2019.
• [5] Prevalence of tuberculosis, HIV/AIDS, and hepatitis; in a prison of Balochistan: a cross-sectional survey.BMC Public Health. 2019 Dec 4;19(1):1631. doi: 10.1186/s12889-019-8011-7.
• [6] The Utility of CSF Xpert MTB/RIF in Diagnosis of Tubercular Meningitis in Children.Indian J Pediatr. 2019 Dec;86(12):1089-1093. doi: 10.1007/s12098-019-03032-0. Epub 2019 Jul 19.
• [7] Melioidosis in patients with suspected tuberculosis in Cambodia: a single-center cross-sectional study.Int J Tuberc Lung Dis. 2018 Dec 1;22(12):1481-1485. doi: 10.5588/ijtld.17.0294.
• [8] Xpert MTB/RIF Ultra improved the diagnosis of paucibacillary tuberculosis: A prospective cohort study.J Infect. 2019 Apr;78(4):311-316. doi: 10.1016/j.jinf.2019.02.010. Epub 2019 Feb 21.
• [9] Benzofuran-isatin-imine hybrids tethered via different length alkyl linkers: Design, synthesis and invitro evaluation of anti-tubercular and anti-bacterial activities as well as cytotoxicity.Eur J Med Chem. 2019 Mar 1;165:323-331. doi: 10.1016/j.ejmech.2019.01.042. Epub 2019 Jan 22.
• [10] Array-based comparative genomic hybridization in early-stage mycosis fungoides: recurrent deletion of tumor suppressor genes BCL7A, SMAC/DIABLO, and RHOF.Genes Chromosomes Cancer. 2008 Dec;47(12):1067-75. doi: 10.1002/gcc.20601.
• [11] miR-3656 expression enhances the chemosensitivity of pancreatic cancer to gemcitabine through modulation of the RHOF/EMT axis.Cell Death Dis. 2017 Oct 19;8(10):e3129. doi: 10.1038/cddis.2017.530.
• [12] Expression of the Rho-family GTPase gene RHOF in lymphocyte subsets and malignant lymphomas.Br J Haematol. 2005 May;129(4):531-3. doi: 10.1111/j.1365-2141.2005.05481.x.
• [13] Recognition of variant Rifin antigens by human antibodies induced during natural Plasmodium falciparum infections.Infect Immun. 2002 Dec;70(12):7013-21. doi: 10.1128/IAI.70.12.7013-7021.2002.
• [14] Burden of Rifampicin- and Methicillin-Resistant Staphylococcus aureus in Italy.Microb Drug Resist. 2018 Jul/Aug;24(6):732-738. doi: 10.1089/mdr.2017.0299. Epub 2017 Nov 29.
• [15] Preparation, in vitro release and antibacterial activity evaluation of rifampicin and moxifloxacin-loaded poly(D,L-lactide-co-glycolide) microspheres.Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):790-798. doi: 10.1080/21691401.2019.1581792.
• [16] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [17] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [20] 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.
• [21] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [22] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [23] Extracellular ATP drives breast cancer cell migration and metastasis via S100A4 production by cancer cells and fibroblasts. Cancer Lett. 2018 Aug 28;430:1-10. doi: 10.1016/j.canlet.2018.04.043. Epub 2018 May 5.
• [24] 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.
• [25] 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.
• [26] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.