Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP8B2UY)

• DOT Name: Putative ATP-dependent RNA helicase TDRD12 (TDRD12)
• Synonyms: EC 3.6.4.13; ES cell-associated transcript 8 protein; Tudor domain-containing protein 12
• Gene Name: TDRD12
• Related Disease: Acute myelogenous leukaemia
• UniProt ID: TDR12_HUMAN
• EC Number: 3.6.4.13
• Pfam ID: PF00270 ; PF00567
• Sequence:
  MLQLLVLKIEDPGCFWVIIKGCSPFLDHDVDYQKLNSAMNDFYNSTCQDIEIKPLTLEEG
  QVCVVYCEELKCWCRAIVKSITSSADQYLAECFLVDFAKNIPVKSKNIRVVVESFMQLPY
  RAKKFSLYCTKPVTLHIDFCRDSTDIVPAKKWDNAAIQYFQNLLKATTQVEARLCAVEED
  TFEVYLYVTIKDEKVCVNDDLVAKNYACYMSPTKNKNLDYLEKPRLNIKSAPSFNKLNPA
  LTLWPMFLQGKDVQGMEDSHGVNFPAQSLQHTWCKGIVGDLRPTATAQDKAVKCNMDSLR
  DSPKDKSEKKHHCISLKDTNKRVESSVYWPAKRGITIYADPDVPEASALSQKSNEKPLRL
  TEKKEYDEKNSCVKLLQFLNPDPLRADGISDLQQLQKLKGLQPPVVVLRNKIKPCLTIDS
  SPLSADLKKALQRNKFPGPSHTESYSWPPIARGCDVVVISHCESNPLLYLLPVLTVLQTG
  ACYKSLPSRNGPLAVIVCPGWKKAQFIFELLGEYSMSSRPLHPVLLTIGLHKEEAKNTKL
  PRGCDVIVTTPYSLLRLLACQSLLFLRLCHLILDEVEVLFLEANEQMFAILDNFKKNIEV
  EERESAPHQIVAVGVHWNKHIEHLIKEFMNDPYIVITAMEEAALYGNVQQVVHLCLECEK
  TSSLLQALDFIPSQAQKTLIFTCSVAETEIVCKVVESSSIFCLKMHKEMIFNLQNVLEQW
  KKKLSSGSQIILALTDDCVPLLAITDATCVIHFSFPASPKVFGGRLYCMSDHFHAEQGSP
  AEQGDKKAKSVLLLTEKDASHAVGVLRYLERADAKVPAELYEFTAGVLEAKEDKKAGRPL
  CPYLKAFGFCKDKRICPDRHRINPETDLPRKLSSQALPSFGYIKIIPFYILNATNYFGRI
  VDKHMDLYATLNAEMNEYFKDSNKTTVEKVEKFGLYGLAEKTLFHRVQVLEVNQKEDAWA
  LDDILVEFIDEGRTGLVTRDQLLHLPEHFHTLPPQAVEFIVCRVKPADNEIEWNPKVTRY
  IHHKIVGKLHDAKVILALGNTVWIDPMVHITNLSSLKTSVIDYNVRAEILSMGMGIDNPE
  HIEQLKKLREDAKIPACEESLSQTPPRVTGTSPAQDQDHPSEEQGGQGTPPAEDAACLQS
  PQPEDTGAEGGAESKTSSENQKPGGYLVFKRWLSSNR
• Function: Probable ATP-binding RNA helicase required during spermatogenesis to repress transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Involved in the secondary piRNAs metabolic process. Acts via the PET complex, a multiprotein complex required during the secondary piRNAs metabolic process for the PIWIL2 slicing-triggered loading of PIWIL4 piRNAs.
• Reactome Pathway: PIWI-interacting RNA (piRNA) biogenesis (R-HSA-5601884)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[1]

1 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 Putative ATP-dependent RNA helicase TDRD12 (TDRD12).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Putative ATP-dependent RNA helicase TDRD12 (TDRD12).	[3]

References

• [1] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [2] 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.
• [3] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.