Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT197C7T)

• DOT Name: TOG array regulator of axonemal microtubules protein 2 (TOGARAM2)
• Synonyms: Crescerin-2
• Gene Name: TOGARAM2
• Related Disease: Narcolepsy
• UniProt ID: TGRM2_HUMAN
• Pfam ID: PF12348
• Sequence:
  MGTRDDVPEAKVLVPVAVYCGSIPRTSAGPRVLPPGSINSSLPHGEGSLQPEPRALLNNE
  EPSQLLRGLGQLGGLKLDTPSKGWQARNGHPRNLRALSLGDQPLVLLPSPESEANSVARD
  TIQIKDKLKKRRLSEGLAASSRASLDPGGGPQGVPLHSTIPRATSQRLLRVPRPMPLIQS
  IPTTPEASGVKEKGLDLPGSIPGPHELRPGAQEAQISWQYLHCNDEKMQKSLGAIVIPPI
  PKARTVAATPSRVPGSLPSPLPPGQGVLTGLRAPRTRLARGSGPREKTPASLEPKPLASP
  IRDRPAAAKKPALPFSQSAPTLTAFSFDCAREACPPLKEEDQKEIGTKIQVTISKSAREK
  MQLKQMKEMELLRRLEEPRTGQELTSQCLGSQRAFMKEGLLPLRGSGTLSVPTRLSGPCR
  NDVSIILRKWASRASLPSIPISRQEPRFARHASANSLPAVLTLGSPEWEEEEEMDLRACK
  ELRPFSNPELGLRDALQCLNSSDWQMKEKGLVSIQRLAACHSEVLTGKLHDVCLVVTGEV
  TNLRSKVSHLAISTLGDLFQALKKNMDQEAEEIARCLLQKMADTNEFIQRAAGQSLRAMV
  ENVTLARSLVVLTSAGVYHRNPLIRKYAAEHLSAVLEQIGAEKLLSGTRDSTDMLVHNLV
  RLAQDSNQDTRFYGRKMVNILMANTKFDAFLKQSLPSYDLQKVMAAIKQQGIEDNDELPS
  AKGRKVLRSLVVCENGLPIKEGLSCNGPRLVGLRSTLQGRGEMVEQLRELTRLLEAKDFR
  SRMEGVGQLLELCKAKTELVTAHLVQVFDAFTPRLQDSNKKVNQWALESFAKMIPLLRES
  LHPMLLSIIITVADNLNSKNSGIYAAAVAVLDAMVESLDNLCLLPALAGRVRFLSGRAVL
  DVTDRLAVLVASVYPRKPQAVERHVLPILWHFLNTATRNGTLPGPSGNIRGVVCRLSRSL
  QEHMGSRLLDFAASQPKHVLKTLQELLDSESLGGSRKATDRGVAPDSKTTGSSYPFQLD

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[1]

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 TOG array regulator of axonemal microtubules protein 2 (TOGARAM2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of TOG array regulator of axonemal microtubules protein 2 (TOGARAM2).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of TOG array regulator of axonemal microtubules protein 2 (TOGARAM2).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of TOG array regulator of axonemal microtubules protein 2 (TOGARAM2).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of TOG array regulator of axonemal microtubules protein 2 (TOGARAM2).	[6]

References

• [1] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] 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.
• [6] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.