Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4OYFSK)

DOT Name Ribonuclease P protein subunit p14 (RPP14)
Gene Name RPP14
Related Disease
Adenocarcinoma ( )
Glioma ( )
Hepatocellular carcinoma ( )
Medulloblastoma ( )
Acute myelogenous leukaemia ( )
Acute myocardial infarction ( )
Advanced cancer ( )
Bladder cancer ( )
Breast neoplasm ( )
Clear cell renal carcinoma ( )
Cystic fibrosis ( )
Familial adenomatous polyposis ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
Liver cirrhosis ( )
Lung cancer ( )
Lung carcinoma ( )
Lymphoma ( )
Neoplasm ( )
Pancreatic cancer ( )
Plasma cell myeloma ( )
Promyelocytic leukaemia ( )
Renal cell carcinoma ( )
Schizophrenia ( )
Severe congenital neutropenia ( )
Sjogren syndrome ( )
Skin cancer ( )
Small lymphocytic lymphoma ( )
Small-cell lung cancer ( )
Squamous cell carcinoma ( )
Systemic lupus erythematosus ( )
Systemic sclerosis ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Lung adenocarcinoma ( )
Pediatric lymphoma ( )
Stroke ( )
Carcinoma ( )
Adult lymphoma ( )
Colorectal carcinoma ( )
Intellectual disability ( )
Melanoma ( )
Rheumatoid arthritis ( )
Type-1/2 diabetes ( )
UniProt ID
RPP14_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
6AHR; 6AHU
Pfam ID
PF01900
Sequence
MPAPAATYERVVYKNPSEYHYMKVCLEFQDCGVGLNAAQFKQLLISAVKDLFGEVDAALP
LDILTYEEKTLSAILRICSSGLVKLWSSLTLLGSYKGKKCAFRVIQVSPFLLALSGNSRE
LVLD
Function Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends.
Reactome Pathway
Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226 )
tRNA processing in the nucleus (R-HSA-6784531 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenocarcinoma DIS3IHTY Definitive Posttranslational Modification [1]
Glioma DIS5RPEH Definitive Biomarker [2]
Hepatocellular carcinoma DIS0J828 Definitive Genetic Variation [3]
Medulloblastoma DISZD2ZL Definitive Biomarker [4]
Acute myelogenous leukaemia DISCSPTN Strong Posttranslational Modification [5]
Acute myocardial infarction DISE3HTG Strong Biomarker [6]
Advanced cancer DISAT1Z9 Strong Altered Expression [7]
Bladder cancer DISUHNM0 Strong Posttranslational Modification [8]
Breast neoplasm DISNGJLM Strong Biomarker [9]
Clear cell renal carcinoma DISBXRFJ Strong Genetic Variation [10]
Cystic fibrosis DIS2OK1Q Strong Biomarker [11]
Familial adenomatous polyposis DISW53RE Strong Biomarker [12]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [13]
Hepatitis C virus infection DISQ0M8R Strong Altered Expression [14]
Liver cirrhosis DIS4G1GX Strong Genetic Variation [15]
Lung cancer DISCM4YA Strong Posttranslational Modification [16]
Lung carcinoma DISTR26C Strong Posttranslational Modification [16]
Lymphoma DISN6V4S Strong Altered Expression [17]
Neoplasm DISZKGEW Strong Biomarker [7]
Pancreatic cancer DISJC981 Strong Genetic Variation [12]
Plasma cell myeloma DIS0DFZ0 Strong Posttranslational Modification [18]
Promyelocytic leukaemia DISYGG13 Strong Posttranslational Modification [5]
Renal cell carcinoma DISQZ2X8 Strong Genetic Variation [10]
Schizophrenia DISSRV2N Strong Genetic Variation [19]
Severe congenital neutropenia DISES99N Strong Genetic Variation [20]
Sjogren syndrome DISUBX7H Strong Altered Expression [11]
Skin cancer DISTM18U Strong Genetic Variation [21]
Small lymphocytic lymphoma DIS30POX Strong Biomarker [22]
Small-cell lung cancer DISK3LZD Strong Biomarker [23]
Squamous cell carcinoma DISQVIFL Strong Biomarker [24]
Systemic lupus erythematosus DISI1SZ7 Strong Altered Expression [11]
Systemic sclerosis DISF44L6 Strong Altered Expression [11]
Urinary bladder cancer DISDV4T7 Strong Posttranslational Modification [8]
Urinary bladder neoplasm DIS7HACE Strong Posttranslational Modification [8]
Breast cancer DIS7DPX1 moderate Genetic Variation [25]
Breast carcinoma DIS2UE88 moderate Genetic Variation [25]
Lung adenocarcinoma DISD51WR moderate Altered Expression [26]
Pediatric lymphoma DIS51BK2 moderate Altered Expression [17]
Stroke DISX6UHX moderate Genetic Variation [27]
Carcinoma DISH9F1N Disputed Biomarker [28]
Adult lymphoma DISK8IZR Limited Altered Expression [17]
Colorectal carcinoma DIS5PYL0 Limited Posttranslational Modification [29]
Intellectual disability DISMBNXP Limited Biomarker [30]
Melanoma DIS1RRCY Limited Biomarker [31]
Rheumatoid arthritis DISTSB4J Limited Genetic Variation [32]
Type-1/2 diabetes DISIUHAP Limited Genetic Variation [33]
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⏷ Show the Full List of 46 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Ribonuclease P protein subunit p14 (RPP14). [34]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Ribonuclease P protein subunit p14 (RPP14). [35]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Ribonuclease P protein subunit p14 (RPP14). [36]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Ribonuclease P protein subunit p14 (RPP14). [37]
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References

1 EBV-infection in cardiac and non-cardiac gastric adenocarcinomas is associated with promoter methylation of p16, p14 and APC, but not hMLH1.Cell Oncol (Dordr). 2011 Jun;34(3):209-14. doi: 10.1007/s13402-011-0028-6. Epub 2011 May 3.
2 Frequent and variable abnormalities in p14 tumor suppressor gene in glioma cell lines.Brain Tumor Pathol. 2008;25(1):9-17. doi: 10.1007/s10014-007-0226-0. Epub 2008 Apr 16.
3 Role of P14 and MGMT gene methylation in hepatocellular carcinomas: a meta-analysis.Asian Pac J Cancer Prev. 2014;15(16):6591-6. doi: 10.7314/apjcp.2014.15.16.6591.
4 Frequent but borderline methylation of p16 (INK4a) and TIMP3 in medulloblastoma and sPNET revealed by quantitative analyses.J Neurooncol. 2007 May;83(1):17-29. doi: 10.1007/s11060-006-9309-8. Epub 2007 Jan 6.
5 Epigenetic dysregulation of the DAP kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in acute leukaemias.J Clin Pathol. 2008 Jul;61(7):844-7. doi: 10.1136/jcp.2007.047324.
6 Regenerative Potential of Neonatal Porcine Hearts.Circulation. 2018 Dec 11;138(24):2809-2816. doi: 10.1161/CIRCULATIONAHA.118.034886.
7 An Oncolytic Adenovirus Vector Expressing p14 FAST Protein Induces Widespread Syncytium Formation and Reduces Tumor Growth Rate InVivo.Mol Ther Oncolytics. 2019 May 15;14:107-120. doi: 10.1016/j.omto.2019.05.001. eCollection 2019 Sep 27.
8 Hypermethylation of E-cadherin, p16, p14, and RASSF1A genes in pathologically normal urothelium predict bladder recurrence of bladder cancer after transurethral resection.Urol Oncol. 2012 Mar-Apr;30(2):177-81. doi: 10.1016/j.urolonc.2010.01.002. Epub 2010 Aug 25.
9 Association of Mouse Mammary Tumor Virus With Human Breast Cancer: Histology, Immunohistochemistry and Polymerase Chain Reaction Analyses.Front Oncol. 2018 May 7;8:141. doi: 10.3389/fonc.2018.00141. eCollection 2018.
10 Major role for a 3p21 region and lack of involvement of the t(3;8) breakpoint region in the development of renal cell carcinoma suggested by loss of heterozygosity analysis.Genes Chromosomes Cancer. 1996 Jan;15(1):64-72. doi: 10.1002/(SICI)1098-2264(199601)15:1<64::AID-GCC9>3.0.CO;2-2.
11 Myeloid calcium binding proteins: expression in the differentiated HL-60 cells and detection in sera of patients with connective tissue diseases.J Biochem. 1990 Oct;108(4):650-3. doi: 10.1093/oxfordjournals.jbchem.a123257.
12 CDKN2A germline mutations in familial pancreatic cancer.Ann Surg. 2002 Dec;236(6):730-7. doi: 10.1097/00000658-200212000-00005.
13 Promoter hypermethylation of p14 (ARF) , RB, and INK4 gene family in hepatocellular carcinoma with hepatitis B virus infection.Tumour Biol. 2014 Mar;35(3):2795-802. doi: 10.1007/s13277-013-1372-0. Epub 2013 Nov 20.
14 Hepatitis C virus Core overcomes all-trans retinoic acid-induced apoptosis in human hepatoma cells by inhibiting p14 expression via DNA methylation.Oncotarget. 2017 Aug 18;8(49):85584-85598. doi: 10.18632/oncotarget.20337. eCollection 2017 Oct 17.
15 Studying the frequency of aberrant DNA methylation of APC, P14, and E-cadherin genes in HCV-related hepatocarcinogenesis.Cancer Biomark. 2018;22(3):503-509. doi: 10.3233/CBM-171156.
16 Aberrant p16 promoter methylation in smokers and former smokers with nonsmall cell lung cancer.Int J Cancer. 2003 Oct 10;106(6):913-8. doi: 10.1002/ijc.11322.
17 Primary malignant lymphoma of the brain: frequent abnormalities and inactivation of p14 tumor suppressor gene.Cancer Sci. 2005 Jan;96(1):38-41. doi: 10.1111/j.1349-7006.2005.00003.x.
18 Epigenetic dysregulation of the death-associated protein kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myeloma. J Clin Pathol. 2007 Jun;60(6):664-9. doi: 10.1136/jcp.2006.038331.
19 Early Development of Parvalbumin-, Somatostatin-, and Cholecystokinin-Expressing Neurons in Rat Brain following Prenatal Immune Activation and Maternal Iron Deficiency.Dev Neurosci. 2016;38(5):342-353. doi: 10.1159/000454677. Epub 2017 Feb 18.
20 Clinical implications of ELA2-, HAX1-, and G-CSF-receptor (CSF3R) mutations in severe congenital neutropenia.Br J Haematol. 2009 Feb;144(4):459-67. doi: 10.1111/j.1365-2141.2008.07425.x. Epub 2008 Dec 10.
21 p14ARF hypermethylation is common but INK4a-ARF locus or p53 mutations are rare in Merkel cell carcinoma.J Invest Dermatol. 2008 Jul;128(7):1788-96. doi: 10.1038/sj.jid.5701256. Epub 2008 Jan 24.
22 Frequent DAP kinase but not p14 or Apaf-1 hypermethylation in B-cell chronic lymphocytic leukemia.J Hum Genet. 2006;51(9):832-838. doi: 10.1007/s10038-006-0029-x. Epub 2006 Aug 3.
23 A 2.5-Mb physical map within 3p21.1 spans the breakpoint associated with Greig cephalopolysyndactyly syndrome.Genomics. 1991 Sep;11(1):93-102. doi: 10.1016/0888-7543(91)90105-n.
24 Frequency of genetic and epigenetic alterations of p14ARF and p16INK4A in head and neck cancer in a Hungarian population.Pathol Oncol Res. 2014 Oct;20(4):923-9. doi: 10.1007/s12253-014-9775-9. Epub 2014 Apr 9.
25 Promoter hypermethylation of RAR2, DAPK, hMLH1, p14, and p15 is associated with progression of breast cancer: A PRISMA-compliant meta-analysis.Medicine (Baltimore). 2018 Dec;97(51):e13666. doi: 10.1097/MD.0000000000013666.
26 Adenovirus-Mediated Expression of the p14 Fusion-Associated Small Transmembrane Protein Promotes Cancer Cell Fusion and Apoptosis In Vitro but Does Not Provide Therapeutic Efficacy in a Xenograft Mouse Model of Cancer.PLoS One. 2016 Mar 17;11(3):e0151516. doi: 10.1371/journal.pone.0151516. eCollection 2016.
27 Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System.Front Neural Circuits. 2017 Jun 29;11:47. doi: 10.3389/fncir.2017.00047. eCollection 2017.
28 p14 expression differences in ovarian benign, borderline and malignant epithelial tumors.J Ovarian Res. 2016 Oct 22;9(1):69. doi: 10.1186/s13048-016-0275-2.
29 18q loss of heterozygosity in microsatellite stable colorectal cancer is correlated with CpG island methylator phenotype-negative (CIMP-0) and inversely with CIMP-low and CIMP-high.BMC Cancer. 2007 May 2;7:72. doi: 10.1186/1471-2407-7-72.
30 Partial tetrasomy with triplication of chromosome (5) (p14-p15.33) in a patient with severe multiple congenital anomalies.Am J Med Genet. 1998 Sep 1;79(2):103-7.
31 Mutual exclusivity analysis of genetic and epigenetic drivers in melanoma identifies a link between p14 ARF and RAR signaling.Mol Cancer Res. 2013 Oct;11(10):1166-78. doi: 10.1158/1541-7786.MCR-13-0006. Epub 2013 Jul 12.
32 Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.Hum Mol Genet. 2019 Mar 1;28(5):858-874. doi: 10.1093/hmg/ddy395.
33 Islet biology, the CDKN2A/B locus and type 2 diabetes risk.Diabetologia. 2016 Aug;59(8):1579-93. doi: 10.1007/s00125-016-3967-7. Epub 2016 May 7.
34 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
35 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
36 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
37 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.