Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSJ0Z1Y)

DOT Name U4/U6 small nuclear ribonucleoprotein Prp31 (PRPF31)
Synonyms Pre-mRNA-processing factor 31; Serologically defined breast cancer antigen NY-BR-99; U4/U6 snRNP 61 kDa protein; Protein 61K; hPrp31
Gene Name PRPF31
Related Disease
PRPF31-related retinopathy ( )
Retinitis pigmentosa 11 ( )
Acute myelogenous leukaemia ( )
Advanced cancer ( )
Atrial fibrillation ( )
Bladder cancer ( )
Breast cancer ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Cervical cancer ( )
Cervical carcinoma ( )
Childhood acute lymphoblastic leukemia ( )
Clear cell renal carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Epithelial ovarian cancer ( )
Gastric cancer ( )
Glioma ( )
Hepatocellular carcinoma ( )
Inherited retinal dystrophy ( )
Laryngeal squamous cell carcinoma ( )
Liver cancer ( )
Lung cancer ( )
Lung carcinoma ( )
Non-alcoholic fatty liver disease ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Renal cell carcinoma ( )
Stomach cancer ( )
Systemic sclerosis ( )
Thyroid gland papillary carcinoma ( )
Tuberculosis ( )
Type-1 diabetes ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Age-related macular degeneration ( )
Breast carcinoma ( )
Lung adenocarcinoma ( )
Osteoarthritis ( )
Polycystic ovarian syndrome ( )
Retinopathy ( )
Retinitis pigmentosa ( )
Ankylosing spondylitis ( )
Blindness ( )
Neuroblastoma ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Pancreatic cancer ( )
Squamous cell carcinoma ( )
UniProt ID
PRP31_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2OZB; 3JCR; 3SIU; 3SIV; 5O9Z; 6AH0; 6AHD; 6QW6; 6QX9
Pfam ID
PF01798 ; PF09785
Sequence
MSLADELLADLEEAAEEEEGGSYGEEEEEPAIEDVQEETQLDLSGDSVKTIAKLWDSKMF
AEIMMKIEEYISKQAKASEVMGPVEAAPEYRVIVDANNLTVEIENELNIIHKFIRDKYSK
RFPELESLVPNALDYIRTVKELGNSLDKCKNNENLQQILTNATIMVVSVTASTTQGQQLS
EEELERLEEACDMALELNASKHRIYEYVESRMSFIAPNLSIIIGASTAAKIMGVAGGLTN
LSKMPACNIMLLGAQRKTLSGFSSTSVLPHTGYIYHSDIVQSLPPDLRRKAARLVAAKCT
LAARVDSFHESTEGKVGYELKDEIERKFDKWQEPPPVKQVKPLPAPLDGQRKKRGGRRYR
KMKERLGLTEIRKQANRMSFGEIEEDAYQEDLGFSLGHLGKSGSGRVRQTQVNEATKARI
SKTLQRTLQKQSVVYGGKSTIRDRSSGTASSVAFTPLQGLEIVNPQAAEKKVAEANQKYF
SSMAEFLKVKGEKSGLMST
Function Involved in pre-mRNA splicing as component of the spliceosome. Required for the assembly of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome.
Tissue Specificity Ubiquitously expressed.
KEGG Pathway
Spliceosome (hsa03040 )
Reactome Pathway
mRNA Splicing - Major Pathway (R-HSA-72163 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
PRPF31-related retinopathy DISC0BYD Definitive Autosomal dominant [1]
Retinitis pigmentosa 11 DISZ09B1 Definitive Autosomal dominant [2]
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Atrial fibrillation DIS15W6U Strong Biomarker [5]
Bladder cancer DISUHNM0 Strong Altered Expression [6]
Breast cancer DIS7DPX1 Strong Biomarker [7]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Strong Altered Expression [8]
Cervical cancer DISFSHPF Strong Biomarker [9]
Cervical carcinoma DIST4S00 Strong Biomarker [9]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Biomarker [10]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [11]
Colon cancer DISVC52G Strong Altered Expression [12]
Colon carcinoma DISJYKUO Strong Altered Expression [12]
Colorectal carcinoma DIS5PYL0 Strong Genetic Variation [13]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [9]
Gastric cancer DISXGOUK Strong Altered Expression [14]
Glioma DIS5RPEH Strong Biomarker [15]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [16]
Inherited retinal dystrophy DISGGL77 Strong Genetic Variation [17]
Laryngeal squamous cell carcinoma DIS9UUVF Strong Biomarker [18]
Liver cancer DISDE4BI Strong Altered Expression [8]
Lung cancer DISCM4YA Strong Genetic Variation [19]
Lung carcinoma DISTR26C Strong Genetic Variation [19]
Non-alcoholic fatty liver disease DISDG1NL Strong Altered Expression [20]
Ovarian cancer DISZJHAP Strong Biomarker [9]
Ovarian neoplasm DISEAFTY Strong Biomarker [9]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [11]
Stomach cancer DISKIJSX Strong Altered Expression [14]
Systemic sclerosis DISF44L6 Strong Biomarker [21]
Thyroid gland papillary carcinoma DIS48YMM Strong Genetic Variation [22]
Tuberculosis DIS2YIMD Strong Genetic Variation [23]
Type-1 diabetes DIS7HLUB Strong Biomarker [24]
Urinary bladder cancer DISDV4T7 Strong Biomarker [25]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [25]
Age-related macular degeneration DIS0XS2C moderate Genetic Variation [26]
Breast carcinoma DIS2UE88 moderate Biomarker [7]
Lung adenocarcinoma DISD51WR moderate Genetic Variation [27]
Osteoarthritis DIS05URM moderate Biomarker [28]
Polycystic ovarian syndrome DISZ2BNG moderate Biomarker [29]
Retinopathy DISB4B0F moderate Altered Expression [30]
Retinitis pigmentosa DISCGPY8 Supportive Autosomal dominant [31]
Ankylosing spondylitis DISRC6IR Limited Genetic Variation [32]
Blindness DISTIM10 Limited Genetic Variation [33]
Neuroblastoma DISVZBI4 Limited Biomarker [34]
Non-insulin dependent diabetes DISK1O5Z Limited Genetic Variation [35]
Non-small-cell lung cancer DIS5Y6R9 Limited Biomarker [36]
Pancreatic cancer DISJC981 Limited Biomarker [37]
Squamous cell carcinoma DISQVIFL Limited Biomarker [4]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 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 U4/U6 small nuclear ribonucleoprotein Prp31 (PRPF31). [38]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the methylation of U4/U6 small nuclear ribonucleoprotein Prp31 (PRPF31). [39]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of U4/U6 small nuclear ribonucleoprotein Prp31 (PRPF31). [41]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of U4/U6 small nuclear ribonucleoprotein Prp31 (PRPF31). [43]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of U4/U6 small nuclear ribonucleoprotein Prp31 (PRPF31). [44]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of U4/U6 small nuclear ribonucleoprotein Prp31 (PRPF31). [44]
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⏷ Show the Full List of 6 Drug(s)
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of U4/U6 small nuclear ribonucleoprotein Prp31 (PRPF31). [40]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of U4/U6 small nuclear ribonucleoprotein Prp31 (PRPF31). [42]
PP-242 DM2348V Investigative PP-242 increases the expression of U4/U6 small nuclear ribonucleoprotein Prp31 (PRPF31). [45]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
3 Expression profile analysis of long non-coding RNA in acute myeloid leukemia by microarray and bioinformatics.Cancer Sci. 2018 Feb;109(2):340-353. doi: 10.1111/cas.13465. Epub 2018 Jan 27.
4 RP11-284F21.9 promotes oral squamous cell carcinoma development via the miR-383-5p/MAL2 axis.J Oral Pathol Med. 2020 Jan;49(1):21-29. doi: 10.1111/jop.12946. Epub 2019 Sep 27.
5 Identification of functional lncRNAs in atrial fibrillation by integrative analysis of the lncRNA-mRNA network based on competing endogenous RNAs hypothesis.J Cell Physiol. 2019 Jul;234(7):11620-11630. doi: 10.1002/jcp.27819. Epub 2018 Nov 27.
6 Identifying Cancer Driver lncRNAs Bridged by Functional Effectors through Integrating Multi-omics Data in Human Cancers.Mol Ther Nucleic Acids. 2019 Sep 6;17:362-373. doi: 10.1016/j.omtn.2019.05.030. Epub 2019 Jun 13.
7 Integrative transcriptome data mining for identification of core lncRNAs in breast cancer.PeerJ. 2019 Oct 7;7:e7821. doi: 10.7717/peerj.7821. eCollection 2019.
8 Dependence of artesunate on long noncoding RNA-RP11 to inhibit epithelial-mesenchymal transition of hepatocellular carcinoma.J Cell Biochem. 2019 Apr;120(4):6026-6034. doi: 10.1002/jcb.27889. Epub 2018 Oct 18.
9 Long non-coding RNA RP11-552M11.4 favors tumorigenesis and development of cervical cancer via modulating miR-3941/ATF1 signaling.Int J Biol Macromol. 2019 Jun 1;130:24-33. doi: 10.1016/j.ijbiomac.2019.02.083. Epub 2019 Feb 18.
10 A childhood acute lymphoblastic leukemia-specific lncRNA implicated in prednisolone resistance, cell proliferation, and migration.Oncotarget. 2017 Jan 31;8(5):7477-7488. doi: 10.18632/oncotarget.13936.
11 LncRNA RP11-436H11.5, functioning as a competitive endogenous RNA, upregulates BCL-W expression by sponging miR-335-5p and promotes proliferation and invasion in renal cell carcinoma.Mol Cancer. 2017 Oct 25;16(1):166. doi: 10.1186/s12943-017-0735-3.
12 Downregulation of LncRNA-RP11-317J10.2 promotes cell proliferation and invasion and predicts poor prognosis in colorectal cancer.Scand J Gastroenterol. 2018 Jan;53(1):38-45. doi: 10.1080/00365521.2017.1392597. Epub 2017 Oct 26.
13 Polymorphisms of a novel long non-coding RNA RP11-108K3.2 with colorectal cancer susceptibility and their effects on its expression.Int J Biol Markers. 2020 Mar;35(1):3-9. doi: 10.1177/1724600819888512. Epub 2019 Dec 2.
14 DC-SIGN mediates gastric cancer progression by regulating the JAK2/STAT3 signaling pathway and affecting LncRNA RP11-181G12.2 expression.Biomed Pharmacother. 2020 Jan;121:109644. doi: 10.1016/j.biopha.2019.109644. Epub 2019 Nov 19.
15 The binding of lncRNA RP11-732M18.3 with 14-3-3 / accelerates p21 degradation and promotes glioma growth.EBioMedicine. 2019 Jul;45:58-69. doi: 10.1016/j.ebiom.2019.06.002. Epub 2019 Jun 13.
16 Genome-Wide Screening and Functional Analysis Identifies Tumor Suppressor Long Noncoding RNAs Epigenetically Silenced in Hepatocellular Carcinoma.Cancer Res. 2019 Apr 1;79(7):1305-1317. doi: 10.1158/0008-5472.CAN-18-1659. Epub 2019 Feb 4.
17 Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease.Ophthalmology. 2016 May;123(5):1143-50. doi: 10.1016/j.ophtha.2016.01.009. Epub 2016 Feb 9.
18 Functional significance of the long non-coding RNA RP11-169D4.1 as a metastasis suppressor in laryngeal squamous cell carcinoma by regulating CDH1.Oncol Rep. 2017 Jul;38(1):211-220. doi: 10.3892/or.2017.5645. Epub 2017 May 16.
19 Integrating expression-related SNPs into genome-wide gene- and pathway-based analyses identified novel lung cancer susceptibility genes.Int J Cancer. 2018 Apr 15;142(8):1602-1610. doi: 10.1002/ijc.31182. Epub 2017 Dec 12.
20 Comprehensive bioinformatics analysis of critical lncRNAs, mRNAs and miRNAs in nonalcoholic fatty liver disease.Mol Med Rep. 2019 Apr;19(4):2649-2659. doi: 10.3892/mmr.2019.9931. Epub 2019 Feb 5.
21 Disease-related autoantibody profile in patients with systemic sclerosis.Autoimmunity. 2017 Nov;50(7):414-421. doi: 10.1080/08916934.2017.1357699. Epub 2017 Jul 27.
22 A novel RNA sequencing-based risk score model to predict papillary thyroid carcinoma recurrence.Clin Exp Metastasis. 2020 Apr;37(2):257-267. doi: 10.1007/s10585-019-10011-4. Epub 2019 Dec 2.
23 Genetic polymorphisms of long noncoding RNA RP11-37B2.1 associate with susceptibility of tuberculosis and adverse events of antituberculosis drugs in west China.J Clin Lab Anal. 2019 Jun;33(5):e22880. doi: 10.1002/jcla.22880. Epub 2019 Mar 28.
24 Long non-coding RNAs in nucleus pulposus cell function and intervertebral disc degeneration.Cell Prolif. 2018 Oct;51(5):e12483. doi: 10.1111/cpr.12483. Epub 2018 Jul 24.
25 LncRNA RP11-79H23.3 Functions as a Competing Endogenous RNA to Regulate PTEN Expression through Sponging hsa-miR-107 in the Development of Bladder Cancer.Int J Mol Sci. 2018 Aug 26;19(9):2531. doi: 10.3390/ijms19092531.
26 A novel PRPF31 mutation in a large Chinese family with autosomal dominant retinitis pigmentosa and macular degeneration.PLoS One. 2013 Nov 11;8(11):e78274. doi: 10.1371/journal.pone.0078274. eCollection 2013.
27 Systematic identification of lincRNA-based prognostic biomarkers by integrating lincRNA expression and copy number variation in lung adenocarcinoma.Int J Cancer. 2019 Apr 1;144(7):1723-1734. doi: 10.1002/ijc.31865. Epub 2018 Dec 12.
28 Knockdown of Long Non-Coding RNA RP11-445H22.4 Alleviates LPS-Induced Injuries by Regulation of MiR-301a in Osteoarthritis.Cell Physiol Biochem. 2018;45(2):832-843. doi: 10.1159/000487175. Epub 2018 Jan 31.
29 Polycystic Ovary Syndrome: Novel and Hub lncRNAs in the Insulin Resistance-Associated lncRNA-mRNA Network.Front Genet. 2019 Aug 22;10:772. doi: 10.3389/fgene.2019.00772. eCollection 2019.
30 Expression of PRPF31 and TFPT: regulation in health and retinal disease.Hum Mol Genet. 2012 Sep 15;21(18):4126-37. doi: 10.1093/hmg/dds242. Epub 2012 Jun 20.
31 Nonsyndromic Retinitis Pigmentosa Overview. 2000 Aug 4 [updated 2023 Apr 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
32 Association of Long Noncoding RNAs Polymorphisms With Ankylosing Spondylitis, Vogt-Koyanagi-Harada Disease, and Behcet's Disease.Invest Ophthalmol Vis Sci. 2018 Feb 1;59(2):1158-1166. doi: 10.1167/iovs.17-23247.
33 CNOT3 is a modifier of PRPF31 mutations in retinitis pigmentosa with incomplete penetrance.PLoS Genet. 2012;8(11):e1003040. doi: 10.1371/journal.pgen.1003040. Epub 2012 Nov 8.
34 Regulatory effects of the long noncoding RNA RP11?43N12.1 and microRNA?24?p axis on the neuronal apoptosis induced by the inflammatory reactions of microglia.Int J Mol Med. 2018 Sep;42(3):1741-1755. doi: 10.3892/ijmm.2018.3736. Epub 2018 Jun 20.
35 Genome-Wide Assessment for RestingHeart Rate and Shared Genetics WithCardiometabolic Traits and Type 2 Diabetes.J Am Coll Cardiol. 2019 Oct 29;74(17):2162-2174. doi: 10.1016/j.jacc.2019.08.1055.
36 Exosome-mediated transfer of lncRNA RP11?38N2.4 promotes erlotinib resistance in non-small cell lung cancer.Int J Oncol. 2018 Aug;53(2):527-538. doi: 10.3892/ijo.2018.4412. Epub 2018 May 17.
37 Depletion of the lncRNA RP11-567G11.1 inhibits pancreatic cancer progression.Biomed Pharmacother. 2019 Apr;112:108685. doi: 10.1016/j.biopha.2019.108685. Epub 2019 Feb 23.
38 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.
39 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
40 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.
41 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
42 Benzo[a]pyrene treatment leads to changes in nuclear protein expression and alternative splicing. Mutat Res. 2010 Apr 1;686(1-2):47-56. doi: 10.1016/j.mrfmmm.2010.01.015. Epub 2010 Jan 25.
43 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
44 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.
45 Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.