Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDDWU5Q)

• DOT Name: PR domain zinc finger protein 10 (PRDM10)
• Synonyms: EC 2.1.1.-; PR domain-containing protein 10; Tristanin
• Gene Name: PRDM10
• Related Disease:
  Allergic rhinitis
  Familial adenomatous polyposis 2
  Rheumatoid arthritis
  Soft tissue neoplasm
  Sarcoma
  Soft tissue sarcoma
  Birt-Hogg-Dube syndrome 2
  Coronary atherosclerosis
  Coronary heart disease
  Type-1 diabetes
• UniProt ID: PRD10_HUMAN
• PDB ID: 3IHX
• EC Number: 2.1.1.-
• Pfam ID: PF21549 ; PF00096 ; PF12874
• Sequence:
  MDSKDESSHVWPTSAEHEQNAAQVHFVPDTGTVAQIVYTDDQVRPPQQVVYTADGASYTS
  VDGPEHTLVYIHPVEAAQTLFTDPGQVAYVQQDATAQQASLPVHNQVLPSIESVDGSDPL
  ATLQTPLGRLEAKEEEDEDEDEDTEEDEEEDGEDTDLDDWEPDPPRPFDPHDLWCEECNN
  AHASVCPKHGPLHPIPNRPVLTRARASLPLVLYIDRFLGGVFSKRRIPKRTQFGPVEGPL
  VRGSELKDCYIHLKVSLDKGDRKERDLHEDLWFELSDETLCNWMMFVRPAQNHLEQNLVA
  YQYGHHVYYTTIKNVEPKQELKVWYAASYAEFVNQKIHDISEEERKVLREQEKNWPCYEC
  NRRFISSEQLQQHLNSHDEKLDVFSRTRGRGRGRGKRRFGPGRRPGRPPKFIRLEITSEN
  GEKSDDGTQDLLHFPTKEQFDEAEPATLNGLDQPEQTTIPIPQLPQETQSSLEHEPETHT
  LHLQPQHEESVVPTQSTLTADDMRRAKRIRLELQNAALQHLFIRKSFRPFKCLQCGKAFR
  EKDKLDQHLRFHGREGNCPLTCDLCNKGFISSTSLESHMKLHSDQKTYSCIFCPESFDRL
  DLLKDHVAIHINDGYFTCPTCKKRFPDFIQVKKHVRSFHSEKIYQCTECDKAFCRPDKLR
  LHMLRHSDRKDFLCSTCGKQFKRKDKLREHMQRMHNPEREAKKADRISRSKTFKPRITST
  DYDSFTFKCRLCMMGFRRRGMLVNHLSKRHPDMKIEEVPELTLPIIKPNRDYFCQYCDKV
  YKSASKRKAHILKNHPGAELPPSIRKLRPAGPGEPDPMLSTHTQLTGTIATPPVCCPHCS
  KQYSSKTKMVQHIRKKHPEFAQLSNTIHTPLTTAVISATPAVLTTDSATGETVVTTDLLT
  QAMTELSQTLTTDYRTPQGDYQRIQYIPVSQSASGLQQPQHIQLQVVQVASATSPHQSQQ
  STVDVGQLHDPQPYPQHAIQVQHIQVSGQPLSPSAQQAQQGLSPSHIQGSSSTQGQALQQ
  QQQQQQNSSVQHTYLPSAWNSFRGYSSEIQMMTLPPGQFVITDSGVATPVTTGQVKAVTS
  GHYVLSESQSELEEKQTSALSGGVQVEPPAHSDSLDPQTNSQQQTTQYIITTTTNGNGSS
  EVHITKP
• Function: Acts as a transcriptional activator of FLNC expression.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[1]
Familial adenomatous polyposis 2	DIS62W3Y	Strong	Biomarker	[2]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[3]
Soft tissue neoplasm	DISP2OHE	Strong	Biomarker	[4]
Sarcoma	DISZDG3U	moderate	Genetic Variation	[5]
Soft tissue sarcoma	DISSN8XB	moderate	Genetic Variation	[5]
Birt-Hogg-Dube syndrome 2	DISJOY0X	Limited	Autosomal dominant	[6]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[7]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[7]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[7]

3 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 PR domain zinc finger protein 10 (PRDM10).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of PR domain zinc finger protein 10 (PRDM10).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of PR domain zinc finger protein 10 (PRDM10).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of PR domain zinc finger protein 10 (PRDM10).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of PR domain zinc finger protein 10 (PRDM10).	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of PR domain zinc finger protein 10 (PRDM10).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of PR domain zinc finger protein 10 (PRDM10).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of PR domain zinc finger protein 10 (PRDM10).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of PR domain zinc finger protein 10 (PRDM10).	[16]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of PR domain zinc finger protein 10 (PRDM10).	[17]

References

• [1] Exploring of the molecular mechanism of rhinitis via bioinformatics methods.Mol Med Rep. 2018 Feb;17(2):3014-3020. doi: 10.3892/mmr.2017.8213. Epub 2017 Dec 7.
• [2] Limiting the Hydrolysis and Oxidation of Maleimide-Peptide Adducts Improves Detection of Protein Thiol Oxidation.J Proteome Res. 2017 May 5;16(5):2004-2015. doi: 10.1021/acs.jproteome.6b01060. Epub 2017 Apr 7.
• [3] Identification of a 3'-Untranslated Genetic Variant of RARB Associated With Carotid Intima-Media Thickness in Rheumatoid Arthritis: A Genome-Wide Association Study.Arthritis Rheumatol. 2019 Mar;71(3):351-360. doi: 10.1002/art.40734. Epub 2019 Jan 18.
• [4] PRDM10-rearranged Soft Tissue Tumor: A Clinicopathologic Study of 9 Cases.Am J Surg Pathol. 2019 Apr;43(4):504-513. doi: 10.1097/PAS.0000000000001207.
• [5] Recurrent PRDM10 gene fusions in undifferentiated pleomorphic sarcoma.Clin Cancer Res. 2015 Feb 15;21(4):864-9. doi: 10.1158/1078-0432.CCR-14-2399. Epub 2014 Dec 16.
• [6] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [7] Genome-wide association analysis of imputed rare variants: application to seven common complex diseases.Genet Epidemiol. 2012 Dec;36(8):785-96. doi: 10.1002/gepi.21675. Epub 2012 Sep 5.
• [8] 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.
• [9] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [10] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [11] 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.
• [12] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [13] Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16669-74. doi: 10.1073/pnas.1108190108. Epub 2011 Sep 26.
• [14] 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.
• [15] 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.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.