Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5POMCQ)

• DOT Name: Acid-sensing ion channel 4 (ASIC4)
• Synonyms: ASIC4; Amiloride-sensitive cation channel 4; Amiloride-sensitive cation channel 4, pituitary
• Gene Name: ASIC4
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Glioma
  Neuroblastoma
  Movement disorder
  Nervous system disease
• UniProt ID: ASIC4_HUMAN
• Pfam ID: PF00858
• Sequence:
  MPIEIVCKIKFAEEDAKPKEKEAGDEQSLLGAVAPGAAPRDLATFASTSTLHGLGRACGP
  GPHGLRRTLWALALLTSLAAFLYQAAGLARGYLTRPHLVAMDPAAPAPVAGFPAVTLCNI
  NRFRHSALSDADIFHLANLTGLPPKDRDGHRAAGLRYPEPDMVDILNRTGHQLADMLKSC
  NFSGHHCSASNFSVVYTRYGKCYTFNADPRSSLPSRAGGMGSGLEIMLDIQQEEYLPIWR
  ETNETSFEAGIRVQIHSQEEPPYIHQLGFGVSPGFQTFVSCQEQRLTYLPQPWGNCRAES
  ELREPELQGYSAYSVSACRLRCEKEAVLQRCHCRMVHMPGNETICPPNIYIECADHTLDS
  LGGGPEGPCFCPTPCNLTRYGKEISMVRIPNRGSARYLARKYNRNETYIRENFLVLDVFF
  EALTSEAMEQRAAYGLSALLGDLGGQMGLFIGASILTLLEILDYIYEVSWDRLKRVWRRP
  KTPLRTSTGGISTLGLQELKEQSPCPSRGRVEGGGVSSLLPNHHHPHGPPGGLFEDFAC
• Function: Probable cation channel with high affinity for sodium. In vitro, has no proton-gated channel activity.
• Tissue Specificity: Expressed in pituitary gland. Weakly expressed in brain, vestibular system and organ of Corti.
• KEGG Pathway: Inflammatory mediator regulation of TRP channels (hsa04750)
• Reactome Pathway: Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Genetic Variation	[1]
Neuroblastoma	DISVZBI4	Strong	Genetic Variation	[1]
Movement disorder	DISOJJ2D	Limited	Genetic Variation	[2]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[2]

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 Acid-sensing ion channel 4 (ASIC4).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Acid-sensing ion channel 4 (ASIC4).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Acid-sensing ion channel 4 (ASIC4).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Acid-sensing ion channel 4 (ASIC4).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Acid-sensing ion channel 4 (ASIC4).	[6]

References

• [1] Integration of gene expression and methylation to unravel biological networks in glioblastoma patients.Genet Epidemiol. 2017 Feb;41(2):136-144. doi: 10.1002/gepi.22028. Epub 2016 Dec 26.
• [2] Acid-sensing ion channel (ASIC) 4 gene: physical mapping, genomic organisation, and evaluation as a candidate for paroxysmal dystonia.Eur J Hum Genet. 2001 Sep;9(9):672-6. doi: 10.1038/sj.ejhg.5200699.
• [3] 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.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] 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.