Details of Drug Off-Target (DOT)

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

• DOT Name: PR domain zinc finger protein 12 (PRDM12)
• Synonyms: EC 2.1.1.-; PR domain-containing protein 12
• Gene Name: PRDM12
• Related Disease:
  Congenital insensitivity to pain-hypohidrosis syndrome
  Hereditary sensory and autonomic neuropathy
  Channelopathy-associated congenital insensitivity to pain, autosomal recessive
  Neoplasm
• UniProt ID: PRD12_HUMAN
• PDB ID: 3EP0
• EC Number: 2.1.1.-
• Pfam ID: PF21549 ; PF00096
• Sequence:
  MMGSVLPAEALVLKTGLKAPGLALAEVITSDILHSFLYGRWRNVLGEQLFEDKSHHASPK
  TAFTAEVLAQSFSGEVQKLSSLVLPAEVIIAQSSIPGEGLGIFSKTWIKAGTEMGPFTGR
  VIAPEHVDICKNNNLMWEVFNEDGTVRYFIDASQEDHRSWMTYIKCARNEQEQNLEVVQI
  GTSIFYKAIEMIPPDQELLVWYGNSHNTFLGIPGVPGLEEDQKKNKHEDFHPADSAAGPA
  GRMRCVICHRGFNSRSNLRSHMRIHTLDKPFVCRFCNRRFSQSSTLRNHVRLHTGERPYK
  CQVCQSAYSQLAGLRAHQKSARHRPPSTALQAHSPALPAPHAHAPALAAAAAAAAAAAAH
  HLPAMVL
• Function: Involved in the positive regulation of histone H3-K9 dimethylation.
• Tissue Specificity: Not found in adult tissues except in dorsal root ganglia.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital insensitivity to pain-hypohidrosis syndrome	DISJ0VWY	Definitive	Autosomal recessive	[1]
Hereditary sensory and autonomic neuropathy	DIS2VOAM	Definitive	Autosomal recessive	[1]
Channelopathy-associated congenital insensitivity to pain, autosomal recessive	DISJ1NV4	Limited	Genetic Variation	[2]
Neoplasm	DISZKGEW	Limited	Biomarker	[3]

2 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 12 (PRDM12).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of PR domain zinc finger protein 12 (PRDM12).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PR domain zinc finger protein 12 (PRDM12).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of PR domain zinc finger protein 12 (PRDM12).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of PR domain zinc finger protein 12 (PRDM12).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of PR domain zinc finger protein 12 (PRDM12).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of PR domain zinc finger protein 12 (PRDM12).	[9]

References

• [1] Transcriptional regulator PRDM12 is essential for human pain perception. Nat Genet. 2015 Jul;47(7):803-8. doi: 10.1038/ng.3308. Epub 2015 May 25.
• [2] Prdm12 Directs Nociceptive Sensory Neuron Development by Regulating the Expression of the NGF Receptor TrkA.Cell Rep. 2019 Mar 26;26(13):3522-3536.e5. doi: 10.1016/j.celrep.2019.02.097.
• [3] Quantitative PCR identifies a minimal deleted region of 120 kb extending from the Philadelphia chromosome ABL translocation breakpoint in chronic myeloid leukemia with poor outcome.Leukemia. 2003 Jul;17(7):1313-23. doi: 10.1038/sj.leu.2402969.
• [4] 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.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] 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.
• [7] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.