Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWDR4EX)

• DOT Name: PHD finger protein 10 (PHF10)
• Synonyms: BRG1-associated factor 45a; BAF45a; XAP135
• Gene Name: PHF10
• Related Disease:
  Neoplasm
  Gastric cancer
  Periventricular nodular heterotopia
  Stomach cancer
  Uveal Melanoma
• UniProt ID: PHF10_HUMAN
• PDB ID: 7VDV; 7Y8R
• Pfam ID: PF00628
• Sequence:
  MAAAAGPGAALSPRPCDSDPATPGAQSPKDDNEDNSNDGTQPSKRRRMGSGDSSRSCETS
  SQDLGFSYYPAENLIEYKWPPDETGEYYMLQEQVSEYLGVTSFKRKYPDLERRDLSHKEK
  LYLRELNVITETQCTLGLTALRSDEVIDLMIKEYPAKHAEYSVILQEKERQRITDHYKEY
  SQMQQQNTQKVEASKVPEYIKKAAKKAAEFNSNLNRERMEERRAYFDLQTHVIQVPQGKY
  KVLPTERTKVSSYPVALIPGQFQEYYKRYSPDELRYLPLNTALYEPPLDPELPALDSDGD
  SDDGEDGRGDEKRKNKGTSDSSSGNVSEGESPPDSQEDSFQGRQKSKDKAATPRKDGPKR
  SVLSKSVPGYKPKVIPNAICGICLKGKESNKKGKAESLIHCSQCENSGHPSCLDMTMELV
  SMIKTYPWQCMECKTCIICGQPHHEEEMMFCDMCDRGYHTFCVGLGAIPSGRWICDCCQR
  APPTPRKVGRRGKNSKEG
• Function: Involved in transcription activity regulation by chromatin remodeling. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and is required for the proliferation of neural progenitors. During neural development a switch from a stem/progenitor to a post-mitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to post-mitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth.
• KEGG Pathway:
  ATP-dependent chromatin remodeling (hsa03082)
  Hepatocellular carcinoma (hsa05225)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[2]
Periventricular nodular heterotopia	DISU3ZRI	Strong	Biomarker	[3]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[2]
Uveal Melanoma	DISA7ZGL	Strong	Biomarker	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	PHD finger protein 10 (PHF10) affects the response to substance of Methotrexate.	[14]
Chlorothiazide	DMLHESP	Approved	PHD finger protein 10 (PHF10) increases the Metabolic disorder ADR of Chlorothiazide.	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of PHD finger protein 10 (PHF10).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of PHD finger protein 10 (PHF10).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of PHD finger protein 10 (PHF10).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of PHD finger protein 10 (PHF10).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of PHD finger protein 10 (PHF10).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of PHD finger protein 10 (PHF10).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of PHD finger protein 10 (PHF10).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of PHD finger protein 10 (PHF10).	[12]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of PHD finger protein 10 (PHF10).	[13]

3 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 decreases the methylation of PHD finger protein 10 (PHF10).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of PHD finger protein 10 (PHF10).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of PHD finger protein 10 (PHF10).	[10]

References

• [1] Integrative Copy Number Analysis of Uveal Melanoma Reveals Novel Candidate Genes Involved in Tumorigenesis Including a Tumor Suppressor Role for PHF10/BAF45a.Clin Cancer Res. 2019 Aug 15;25(16):5156-5166. doi: 10.1158/1078-0432.CCR-18-3052. Epub 2019 Jun 21.
• [2] MicroRNA-409-3p regulates cell proliferation and apoptosis by targeting PHF10 in gastric cancer.Cancer Lett. 2012 Jul 28;320(2):189-97. doi: 10.1016/j.canlet.2012.02.030. Epub 2012 Mar 1.
• [3] Periventricular heterotopia in 6q terminal deletion syndrome: role of the C6orf70 gene. Brain. 2013 Nov;136(Pt 11):3378-94. doi: 10.1093/brain/awt249. Epub 2013 Sep 20.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] 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.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [13] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [14] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [15] Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. Pharmacogenomics J. 2014 Feb;14(1):35-40. doi: 10.1038/tpj.2013.3. Epub 2013 Feb 12.