Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWOP87P)

• DOT Name: Transmembrane protein 240 (TMEM240)
• Gene Name: TMEM240
• Related Disease:
  Spinocerebellar ataxia type 21
  Cerebellar ataxia
  Intellectual disability
• UniProt ID: TM240_HUMAN
• Pfam ID: PF15207
• Sequence:
  MSMSANTMIFMILGASVVMAIACLMDMNALLDRFHNYILPHLRGEDRVCHCNCGRHHIHY
  VIPYDGDQSVVDASENYFVTDSVTKQEIDLMLGLLLGFCISWFLVWMDGVLHCAVRAWRA
  GRRYDGSWTWLPKLCSLRELGRRPHRPFEEAAGNMVHVKQKLYHNGHPSPRHL

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Spinocerebellar ataxia type 21	DIS0U436	Definitive	Autosomal dominant	[1]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[2]
Intellectual disability	DISMBNXP	moderate	Genetic Variation	[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 Transmembrane protein 240 (TMEM240).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transmembrane protein 240 (TMEM240).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transmembrane protein 240 (TMEM240).	[6]

References

• [1] The Neurodevelopmental and Motor Phenotype of SCA21 (ATX-TMEM240). J Child Neurol. 2020 Dec;35(14):953-962. doi: 10.1177/0883073820943488. Epub 2020 Jul 24.
• [2] The movement disorder spectrum of SCA21 (ATX-TMEM240): 3 novel families and systematic review of the literature.Parkinsonism Relat Disord. 2019 May;62:215-220. doi: 10.1016/j.parkreldis.2018.11.027. Epub 2018 Nov 29.
• [3] TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment. Brain. 2014 Oct;137(Pt 10):2657-63. doi: 10.1093/brain/awu202. Epub 2014 Jul 28.
• [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] 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.
• [6] 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.