Details of Drug Off-Target (DOT)

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

• DOT Name: Pre-mRNA-processing factor 40 homolog B (PRPF40B)
• Synonyms: Huntingtin yeast partner C; Huntingtin-interacting protein C
• Gene Name: PRPF40B
• Related Disease:
  Acute myelogenous leukaemia
  Myelodysplastic syndrome
  Advanced cancer
  Nephronophthisis
  Schizophrenia
  Pancreatic cancer
• UniProt ID: PR40B_HUMAN
• Pfam ID: PF01846 ; PF00397
• Sequence:
  MMPPPFMPPPGIPPPFPPMGLPPMSQRPPAIPPMPPGILPPMLPPMGAPPPLTQIPGMVP
  PMMPGMLMPAVPVTAATAPGADTASSAVAGTGPPRALWSEHVAPDGRIYYYNADDKQSVW
  EKPSVLKSKAELLLSQCPWKEYKSDTGKPYYYNNQSKESRWTRPKDLDDLEVLVKQEAAG
  KQQQQLPQTLQPQPPQPQPDPPPVPPGPTPVPTGLLEPEPGGSEDCDVLEATQPLEQGFL
  QQLEEGPSSSGQHQPQQEEEESKPEPERSGLSWSNREKAKQAFKELLRDKAVPSNASWEQ
  AMKMVVTDPRYSALPKLSEKKQAFNAYKAQREKEEKEEARLRAKEAKQTLQHFLEQHERM
  TSTTRYRRAEQTFGELEVWAVVPERDRKEVYDDVLFFLAKKEKEQAKQLRRRNIQALKSI
  LDGMSSVNFQTTWSQAQQYLMDNPSFAQDHQLQNMDKEDALICFEEHIRALEREEEEERE
  RARLRERRQQRKNREAFQTFLDELHETGQLHSMSTWMELYPAVSTDVRFANMLGQPGSTP
  LDLFKFYVEELKARFHDEKKIIKDILKDRGFCVEVNTAFEDFAHVISFDKRAAALDAGNI
  KLTFNSLLEKAEAREREREKEEARRMRRREAAFRSMLRQAVPALELGTAWEEVRERFVCD
  SAFEQITLESERIRLFREFLQVLEQTECQHLHTKGRKHGRKGKKHHHKRSHSPSGSESEE
  EELPPPSLRPPKRRRRNPSESGSEPSSSLDSVESGGAALGGRGSPSSHLLGADHGLRKAK
  KPKKKTKKRRHKSNSPESETDPEEKAGKESDEKEQEQDKDRELQQAELPNRSPGFGIKKE
  KTGWDTSESELSEGELERRRRTLLQQLDDHQ
• Function: May be involved in pre-mRNA splicing.
• Tissue Specificity: Expressed in the striatum and cortex of the brain (at protein level). Highly expressed in testis, fetal kidney and fetal brain. Moderately expressed in pancreas, skeletal muscle, placenta, brain and heart. Weakly expressed in colon, ileum, ovary, prostate, spleen, kidney and fetal lung.
• KEGG Pathway: Spliceosome (hsa03040)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Myelodysplastic syndrome	DISYHNUI	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Nephronophthisis	DISXU4HY	Strong	Genetic Variation	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[4]
Pancreatic cancer	DISJC981	moderate	Biomarker	[5]

5 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 Pre-mRNA-processing factor 40 homolog B (PRPF40B).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Pre-mRNA-processing factor 40 homolog B (PRPF40B).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Pre-mRNA-processing factor 40 homolog B (PRPF40B).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Pre-mRNA-processing factor 40 homolog B (PRPF40B).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Pre-mRNA-processing factor 40 homolog B (PRPF40B).	[12]

5 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 Pre-mRNA-processing factor 40 homolog B (PRPF40B).	[10]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Pre-mRNA-processing factor 40 homolog B (PRPF40B).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Pre-mRNA-processing factor 40 homolog B (PRPF40B).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Pre-mRNA-processing factor 40 homolog B (PRPF40B).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Pre-mRNA-processing factor 40 homolog B (PRPF40B).	[13]

References

• [1] The changing mutational landscape of acute myeloid leukemia and myelodysplastic syndrome.Mol Cancer Res. 2013 Aug;11(8):815-27. doi: 10.1158/1541-7786.MCR-12-0695. Epub 2013 May 3.
• [2] Human PRPF40B regulates hundreds of alternative splicing targets and represses a hypoxia expression signature.RNA. 2019 Aug;25(8):905-920. doi: 10.1261/rna.069534.118. Epub 2019 May 14.
• [3] Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity.Kidney Int. 2016 Feb;89(2):468-475. doi: 10.1038/ki.2015.317.
• [4] Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
• [5] SF3A1 and pancreatic cancer: new evidence for the association of the spliceosome and cancer.Oncotarget. 2015 Nov 10;6(35):37750-7. doi: 10.18632/oncotarget.5647.
• [6] 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.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] 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.
• [11] 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.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] 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.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.