Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTES2MES)

• DOT Name: RNA-binding protein 10 (RBM10)
• Synonyms: G patch domain-containing protein 9; RNA-binding motif protein 10; RNA-binding protein S1-1; S1-1
• Gene Name: RBM10
• Related Disease:
  Endometrial cancer
  Endometrial carcinoma
  Adenocarcinoma
  Advanced cancer
  Astrocytoma
  Breast neoplasm
  Cardiac failure
  Clear cell renal carcinoma
  Cleft palate
  Congestive heart failure
  Isolated cleft palate
  Lung carcinoma
  Lung neoplasm
  Neoplasm
  Polydactyly
  TARP syndrome
  Breast cancer
  Small-cell lung cancer
  Breast carcinoma
  Clubfoot
  Lung adenocarcinoma
  Lung cancer
  Renal cell carcinoma
• UniProt ID: RBM10_HUMAN
• PDB ID: 2LXI; 2M2B; 2MXV; 2MXW; 5ZSW; 5ZSY
• Pfam ID: PF01585 ; PF17780 ; PF00076 ; PF00641
• Sequence:
  MEYERRGGRGDRTGRYGATDRSQDDGGENRSRDHDYRDMDYRSYPREYGSQEGKHDYDDS
  SEEQSAEDSYEASPGSETQRRRRRRHRHSPTGPPGFPRDGDYRDQDYRTEQGEEEEEEED
  EEEEEKASNIVMLRMLPQAATEDDIRGQLQSHGVQAREVRLMRNKSSGQSRGFAFVEFSH
  LQDATRWMEANQHSLNILGQKVSMHYSDPKPKINEDWLCNKCGVQNFKRREKCFKCGVPK
  SEAEQKLPLGTRLDQQTLPLGGRELSQGLLPLPQPYQAQGVLASQALSQGSEPSSENAND
  TIILRNLNPHSTMDSILGALAPYAVLSSSNVRVIKDKQTQLNRGFAFIQLSTIVEAAQLL
  QILQALHPPLTIDGKTINVEFAKGSKRDMASNEGSRISAASVASTAIAAAQWAISQASQG
  GEGTWATSEEPPVDYSYYQQDEGYGNSQGTESSLYAHGYLKGTKGPGITGTKGDPTGAGP
  EASLEPGADSVSMQAFSRAQPGAAPGIYQQSAEASSSQGTAANSQSYTIMSPAVLKSELQ
  SPTHPSSALPPATSPTAQESYSQYPVPDVSTYQYDETSGYYYDPQTGLYYDPNSQYYYNA
  QSQQYLYWDGERRTYVPALEQSADGHKETGAPSKEGKEKKEKHKTKTAQQIAKDMERWAR
  SLNKQKENFKNSFQPISSLRDDERRESATADAGYAILEKKGALAERQHTSMDLPKLASDD
  RPSPPRGLVAAYSGESDSEEEQERGGPEREEKLTDWQKLACLLCRRQFPSKEALIRHQQL
  SGLHKQNLEIHRRAHLSENELEALEKNDMEQMKYRDRAAERREKYGIPEPPEPKRRKYGG
  ISTASVDFEQPTRDGLGSDNIGSRMLQAMGWKEGSGLGRKKQGIVTPIEAQTRVRGSGLG
  ARGSSYGVTSTESYKETLHKTMVTRFNEAQ
• Function: May be involved in post-transcriptional processing, most probably in mRNA splicing. Binds to RNA homopolymers, with a preference for poly(G) and poly(U) and little for poly(A). May bind to specific miRNA hairpins.
• Reactome Pathway:
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Endometrial cancer	DISW0LMR	Definitive	Altered Expression	[1]
Endometrial carcinoma	DISXR5CY	Definitive	Altered Expression	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Astrocytoma	DISL3V18	Strong	Altered Expression	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Cardiac failure	DISDC067	Strong	Altered Expression	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[7]
Cleft palate	DIS6G5TF	Strong	Genetic Variation	[8]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[6]
Isolated cleft palate	DISV80CD	Strong	Genetic Variation	[8]
Lung carcinoma	DISTR26C	Strong	Biomarker	[9]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Polydactyly	DIS25BMZ	Strong	Biomarker	[10]
TARP syndrome	DIS7ZSZP	Strong	X-linked	[8]
Breast cancer	DIS7DPX1	moderate	Biomarker	[11]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[12]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[11]
Clubfoot	DISLXT4S	Limited	Genetic Variation	[13]
Lung adenocarcinoma	DISD51WR	Limited	Altered Expression	[11]
Lung cancer	DISCM4YA	Limited	Biomarker	[9]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[7]

4 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 RNA-binding protein 10 (RBM10).	[14]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of RNA-binding protein 10 (RBM10).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of RNA-binding protein 10 (RBM10).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of RNA-binding protein 10 (RBM10).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of RNA-binding protein 10 (RBM10).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RNA-binding protein 10 (RBM10).	[16]
Selenium	DM25CGV	Approved	Selenium increases the expression of RNA-binding protein 10 (RBM10).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RNA-binding protein 10 (RBM10).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of RNA-binding protein 10 (RBM10).	[21]

References

• [1] Alternative splicing of VEGFA is regulated by RBM10 in endometrial cancer.Kaohsiung J Med Sci. 2020 Jan;36(1):13-19. doi: 10.1002/kjm2.12127. Epub 2019 Oct 6.
• [2] Increased cell apoptosis in human lung adenocarcinoma and in vivo tumor growth inhibition by RBM10, a tumor suppressor gene.Oncol Lett. 2017 Oct;14(4):4663-4669. doi: 10.3892/ol.2017.6765. Epub 2017 Aug 17.
• [3] RNA-binding motif protein 10 induces apoptosis and suppresses proliferation by activating p53.Oncogene. 2020 Jan;39(5):1031-1040. doi: 10.1038/s41388-019-1034-9. Epub 2019 Oct 7.
• [4] Differential expression of the RNA-binding motif protein 3 in human astrocytoma.Chin Med J (Engl). 2013;126(10):1948-52.
• [5] The small variant of the apoptosis-associated X-chromosome RBM10 gene is co-expressed with caspase-3 in breast cancer.Cancer Genomics Proteomics. 2008 May-Aug;5(3-4):169-73.
• [6] A Splicing-Independent Function of RBM10 Controls Specific 3' UTR Processing to Regulate Cardiac Hypertrophy.Cell Rep. 2018 Sep 25;24(13):3539-3553. doi: 10.1016/j.celrep.2018.08.077.
• [7] RBM10-TFE3 renal cell carcinoma characterised by paracentric inversion with consistent closely split signals in break-apart fluorescence in-situ hybridisation: study of 10 cases and a literature review.Histopathology. 2019 Aug;75(2):254-265. doi: 10.1111/his.13866. Epub 2019 Jun 25.
• [8] Massively parallel sequencing of exons on the X chromosome identifies RBM10 as the gene that causes a syndromic form of cleft palate. Am J Hum Genet. 2010 May 14;86(5):743-8. doi: 10.1016/j.ajhg.2010.04.007. Epub 2010 May 6.
• [9] Functional role of RBM10 in lung adenocarcinoma proliferation.Int J Oncol. 2019 Feb;54(2):467-478. doi: 10.3892/ijo.2018.4643. Epub 2018 Nov 22.
• [10] Expansion of the TARP syndrome phenotype associated with de novo mutations and mosaicism.Am J Med Genet A. 2014 Jan;164A(1):120-8. doi: 10.1002/ajmg.a.36212. Epub 2013 Nov 20.
• [11] RBM10 truncation in astroblastoma in a patient with history of mandibular ameloblastoma: A case report.Cancer Genet. 2019 Feb;231-232:41-45. doi: 10.1016/j.cancergen.2019.01.001. Epub 2019 Jan 9.
• [12] RBM10 promotes transformation-associated processes in small cell lung cancer and is directly regulated by RBM5.PLoS One. 2017 Jun 29;12(6):e0180258. doi: 10.1371/journal.pone.0180258. eCollection 2017.
• [13] Clinical diagnostic exome evaluation for an infant with a lethal disorder: genetic diagnosis of TARP syndrome and expansion of the phenotype in a patient with a newly reported RBM10 alteration.BMC Med Genet. 2017 Jun 2;18(1):60. doi: 10.1186/s12881-017-0426-3.
• [14] 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.
• [15] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [16] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [17] 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.
• [18] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [19] 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.
• [20] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.