Details of Drug Off-Target (DOT)

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

• DOT Name: PR domain zinc finger protein 13 (PRDM13)
• Synonyms: EC 2.1.1.-; PR domain-containing protein 13
• Gene Name: PRDM13
• Related Disease:
  Glioma
  Triple negative breast cancer
  Malignant tumor of nasopharynx
  Nasopharyngeal carcinoma
  Neoplasm
  Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism
  North Carolina macular dystrophy
  Pontocerebellar hypoplasia, IIA 17
• UniProt ID: PRD13_HUMAN
• EC Number: 2.1.1.-
• Pfam ID: PF21549 ; PF00096
• Sequence:
  MHGAARAPATSVSADCCIPAGLRLGPVPGTFKLGKYLSDRREPGPKKKVRMVRGELVDES
  GGSPLEWIGLIRAARNSQEQTLEAIADLPGGQIFYRALRDVQPGEELTVWYSNSLAQWFD
  IPTTATPTHDEKGEERYICWYCWRTFRYPNSLKAHLRFHCVFSGGGGGAFLHHEHAARQG
  AVPAADGLGLSPKPPAPDFAAPSQAGTLRPHPLGPPPVQACGAREGIKREASSAPSATSP
  TPGKWGQPKKGKEQLDRALDMSGAARGQGHFLGIVGGSSAGVGSLAFYPGVRSAFKPAGL
  ARAAAAAHGDPYREESSSKQGAGLALGRLLGGGRACGRPGSGENSAAGGAGHHHHHHAHH
  HHHPKCLLAGDPPPPPPPGLPCSGALRGFPLLSVPPEEASAFKHVERAPPAAAALPGARY
  AQLPPAPGLPLERCALPPLDPGGLKAYPGGECSHLPAVMPAFTVYNGELLYGSPATTAYY
  PLKLHFGGLLKYPESISYFSGPAAAALSPAELGSLASIDREIAMHNQQLSEMAAGKGRGR
  LDSGTLPPAVAAAGGTGGGGSGGSGAGKPKTGHLCLYCGKLYSRKYGLKIHMRTHTGYKP
  LKCKVCLRPFGDPSNLNKHIRLHAEGNTPYRCEFCGKVLVRRRDLERHVKSRHPGQSLLA
  KAGDGPGAEPGYPPEPGDPKSDDSDVDVCFTDDQSDPEVGGGGERDL
• Function: May be involved in transcriptional regulation. Is required for the differentiation of KISS1-expressing neurons in the arcuate (Arc) nucleus of the hypothalamus. Is a critical regulator of GABAergic cell fate in the cerebellum, required for normal postnatal cerebellar development.
• Tissue Specificity: In the embryo, expressed in neural stem cells of the hindbrain.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[2]
Malignant tumor of nasopharynx	DISTGIGF	moderate	Biomarker	[3]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Biomarker	[3]
Neoplasm	DISZKGEW	moderate	Biomarker	[3]
Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism	DISVT4UQ	Limited	Unknown	[4]
North Carolina macular dystrophy	DISMPOAO	Limited	Autosomal dominant	[5]
Pontocerebellar hypoplasia, IIA 17	DISR9DMQ	Limited	Autosomal recessive	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of PR domain zinc finger protein 13 (PRDM13).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of PR domain zinc finger protein 13 (PRDM13).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of PR domain zinc finger protein 13 (PRDM13).	[10]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of PR domain zinc finger protein 13 (PRDM13).	[13]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of PR domain zinc finger protein 13 (PRDM13).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of PR domain zinc finger protein 13 (PRDM13).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of PR domain zinc finger protein 13 (PRDM13).	[12]

References

• [1] Overexpression of PRDM13 inhibits glioma cells via Rho and GTP enzyme activation protein.Int J Mol Med. 2018 Aug;42(2):966-974. doi: 10.3892/ijmm.2018.3679. Epub 2018 May 14.
• [2] Large-scale in-silico identification of a tumor-specific antigen pool for targeted immunotherapy in triple-negative breast cancer.Oncotarget. 2019 Apr 2;10(26):2515-2529. doi: 10.18632/oncotarget.26808. eCollection 2019 Apr 2.
• [3] Novel tumor antigens identified by autologous antibody screening of childhood medulloblastoma cDNA libraries.Int J Cancer. 2003 Aug 20;106(2):244-51. doi: 10.1002/ijc.11208.
• [4] De novo mutation screening in childhood-onset cerebellar atrophy identifies gain-of-function mutations in the CACNA1G calcium channel gene. Brain. 2018 Jul 1;141(7):1998-2013. doi: 10.1093/brain/awy145.
• [5] A novel duplication of PRMD13 causes North Carolina macular dystrophy: overexpression of PRDM13 orthologue in drosophila eye reproduces the human phenotype. Hum Mol Genet. 2017 Nov 15;26(22):4367-4374. doi: 10.1093/hmg/ddx322.
• [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] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] 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.
• [9] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] 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.
• [12] 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.
• [13] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.