Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0V4EIZ)

• DOT Name: Ras association domain-containing protein 7 (RASSF7)
• Synonyms: HRAS1-related cluster protein 1
• Gene Name: RASSF7
• Related Disease:
  Bladder cancer
  Neuroblastoma
  Adrenocortical carcinoma
  Advanced cancer
  Autism
  Beckwith-Wiedemann syndrome
  Brain neoplasm
  Colon carcinoma
  Epithelial ovarian cancer
  Gastric cancer
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Melanoma
  Multiple endocrine neoplasia type 1
  Neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Squamous cell carcinoma
  Stomach cancer
  Thyroid tumor
  Urinary bladder cancer
  Urinary bladder neoplasm
  Hereditary breast ovarian cancer syndrome
  Aniridia
  Childhood kidney Wilms tumor
  Hepatocellular carcinoma
  Intervertebral disc degeneration
  Leukemia
  Lymphoma
  Type-1 diabetes
  Wilms tumor
• UniProt ID: RASF7_HUMAN
• Pfam ID: PF00788
• Sequence:
  MLLGLAAMELKVWVDGIQRVVCGVSEQTTCQEVVIALAQAIGQTGRFVLVQRLREKERQL
  LPQECPVGAQATCGQFASDVQFVLRRTGPSLAGRPSSDSCPPPERCLIRASLPVKPRAAL
  GCEPRKTLTPEPAPSLSRPGPAAPVTPTPGCCTDLRGLELRVQRNAEELGHEAFWEQELR
  REQAREREGQARLQALSAATAEHAARLQALDAQARALEAELQLAAEAPGPPSPMASATER
  LHQDLAVQERQSAEVQGSLALVSRALEAAERALQAQAQELEELNRELRQCNLQQFIQQTG
  AALPPPPRPDRGPPGTQGPLPPAREESLLGAPSESHAGAQPRPRGGPHDAELLEVAAAPA
  PEWCPLAAQPQAL
• Function: Negatively regulates stress-induced JNK activation and apoptosis by promoting MAP2K7 phosphorylation and inhibiting its ability to activate JNK. Following prolonged stress, anti-apoptotic effect stops because of degradation of RASSF7 protein via the ubiquitin-proteasome pathway. Required for the activation of AURKB and chromosomal congression during mitosis where it stimulates microtubule polymerization.

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Definitive	Genetic Variation	[1]
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[2]
Adrenocortical carcinoma	DISZF4HX	Strong	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Autism	DISV4V1Z	Strong	Genetic Variation	[5]
Beckwith-Wiedemann syndrome	DISH15GR	Strong	Biomarker	[6]
Brain neoplasm	DISY3EKS	Strong	Genetic Variation	[7]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[9]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[10]
Lung cancer	DISCM4YA	Strong	Altered Expression	[11]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[11]
Lung neoplasm	DISVARNB	Strong	Genetic Variation	[12]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[13]
Multiple endocrine neoplasia type 1	DIS0RJRK	Strong	Genetic Variation	[14]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[11]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[9]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[9]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[16]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[10]
Thyroid tumor	DISLVKMD	Strong	Genetic Variation	[17]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[1]
Hereditary breast ovarian cancer syndrome	DISWDUGU	moderate	Genetic Variation	[18]
Aniridia	DIS1P333	Limited	Biomarker	[19]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Biomarker	[19]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[20]
Intervertebral disc degeneration	DISG3AIM	Limited	Altered Expression	[21]
Leukemia	DISNAKFL	Limited	Biomarker	[22]
Lymphoma	DISN6V4S	Limited	Genetic Variation	[23]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[21]
Wilms tumor	DISB6T16	Limited	Biomarker	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Ras association domain-containing protein 7 (RASSF7) decreases the response to substance of Arsenic trioxide.	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Ras association domain-containing protein 7 (RASSF7).	[24]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Ras association domain-containing protein 7 (RASSF7).	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ras association domain-containing protein 7 (RASSF7).	[25]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ras association domain-containing protein 7 (RASSF7).	[26]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Ras association domain-containing protein 7 (RASSF7).	[27]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Ras association domain-containing protein 7 (RASSF7).	[28]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ras association domain-containing protein 7 (RASSF7).	[29]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ras association domain-containing protein 7 (RASSF7).	[30]

References

• [1] HRAS1 variable number of tandem repeats polymorphism and risk of bladder cancer.Int J Cancer. 2002 Aug 1;100(4):414-8. doi: 10.1002/ijc.10497.
• [2] The RASSF gene family members RASSF5, RASSF6 and RASSF7 show frequent DNA methylation in neuroblastoma.Mol Cancer. 2012 Jun 13;11:40. doi: 10.1186/1476-4598-11-40.
• [3] Genetic changes in human adrenocortical carcinomas.J Natl Cancer Inst. 1989 Apr 5;81(7):518-23. doi: 10.1093/jnci/81.7.518.
• [4] The non-enzymatic RAS effector RASSF7 inhibits oncogenic c-Myc function.J Biol Chem. 2018 Oct 5;293(40):15691-15705. doi: 10.1074/jbc.RA118.004452. Epub 2018 Aug 23.
• [5] Possible association of c-Harvey-Ras-1 (HRAS-1) marker with autism.Psychiatry Res. 1993 Mar;46(3):261-7. doi: 10.1016/0165-1781(93)90094-w.
• [6] Duplication of HRAS1, INS, and IGF2 is not a common event in Beckwith-Wiedemann syndrome.Ann Genet. 1988;31(4):216-20.
• [7] Rare HRAS1 alleles are a risk factor for the development of brain tumors.Cancer. 2001 Dec 1;92(11):2920-6.
• [8] HRAS1 minisatellite alleles in colorectal carcinoma: relationship to microsatelite instability.Anticancer Res. 2001 Jul-Aug;21(4A):2855-60.
• [9] The HRAS1 minisatellite locus and risk of ovarian cancer.Cancer Res. 2000 Jan 15;60(2):259-61.
• [10] RASSF10 is an epigenetically silenced tumor suppressor in gastric cancer.Oncol Rep. 2014 Apr;31(4):1661-8. doi: 10.3892/or.2014.3039. Epub 2014 Feb 20.
• [11] The coiled-coil domain of oncogene RASSF 7 inhibits hippo signaling and promotes non-small cell lung cancer.Oncotarget. 2017 Aug 12;8(45):78734-78748. doi: 10.18632/oncotarget.20223. eCollection 2017 Oct 3.
• [12] Genetic alterations in cancer knowledge system: analysis of gene mutations in mouse and human liver and lung tumors.Toxicol Sci. 2006 Apr;90(2):400-18. doi: 10.1093/toxsci/kfj101. Epub 2006 Jan 12.
• [13] HRAS1 proto-oncogene polymorphisms in human malignant melanoma: TaqI defined alleles significantly associated with the disease.Oncogene. 1987;2(1):91-5.
• [14] Loss of the same alleles of HRAS1 and D11S151 in two independent pancreatic cancers from a patient with multiple endocrine neoplasia type 1.Cancer Res. 1989 May 15;49(10):2716-21.
• [15] Truncated RASSF7 promotes centrosomal defects and cell death.Dev Biol. 2016 Jan 15;409(2):502-17. doi: 10.1016/j.ydbio.2015.11.001. Epub 2015 Nov 10.
• [16] A region within murine chromosome 7F4, syntenic to the human 11q13 amplicon, is frequently amplified in 4NQO-induced oral cavity tumors.Oncogene. 1997 Sep 4;15(10):1161-70. doi: 10.1038/sj.onc.1201269.
• [17] [Study of HRas1 minisatellite frequencies in children with thyroid papillary cancer].Tsitol Genet. 2004 Jan-Feb;38(1):9-14.
• [18] Ovarian cancer risk in BRCA1 carriers is modified by the HRAS1 variable number of tandem repeat (VNTR) locus.Nat Genet. 1996 Mar;12(3):309-11. doi: 10.1038/ng0396-309.
• [19] HRAS1-selected chromosome transfer generates markers that colocalize aniridia- and genitourinary dysplasia-associated translocation breakpoints and the Wilms tumor gene within band 11p13.Proc Natl Acad Sci U S A. 1987 Aug;84(15):5355-9. doi: 10.1073/pnas.84.15.5355.
• [20] RASSF7 promotes cell proliferation through activating MEK1/2-ERK1/2 signaling pathway in hepatocellular carcinoma.Cell Mol Biol (Noisy-le-grand). 2018 Apr 30;64(5):73-79.
• [21] RASSF7 expression and its regulatory roles on apoptosis in human intervertebral disc degeneration.Int J Clin Exp Pathol. 2015 Dec 1;8(12):16097-103. eCollection 2015.
• [22] HRAS1 and INS genes are relocated but not structurally altered as a result of the t(7;11)(p15;p15) in a clone from a patient with acute myeloid leukaemia (M4).Br J Haematol. 1989 Apr;71(4):481-6. doi: 10.1111/j.1365-2141.1989.tb06306.x.
• [23] Rare HRAS1 alleles outside the VTR region in lymph nodes from patients with malignant lymphoma.Cancer Genet Cytogenet. 1993 Aug;69(1):60-4. doi: 10.1016/0165-4608(93)90115-3.
• [24] 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.
• [25] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [26] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [27] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [28] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [29] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [30] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [31] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [32] 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.