Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1KWTC1)

• DOT Name: Acid-sensing ion channel 5 (ASIC5)
• Synonyms: ASIC5; Amiloride-sensitive cation channel 5; Human intestine Na(+) channel; HINaC
• Gene Name: ASIC5
• Related Disease:
  Cystic fibrosis
  Essential hypertension
  High blood pressure
  Liddle syndrome
  Pelger-Huet anomaly
• UniProt ID: ASIC5_HUMAN
• Pfam ID: PF00858
• Sequence:
  MEQTEKSKVYAENGLLEKIKLCLSKKPLPSPTERKKFDHDFAISTSFHGIHNIVQNRSKI
  RRVLWLVVVLGSVSLVTWQIYIRLLNYFTWPTTTSIEVQYVEKMEFPAVTFCNLNRFQTD
  AVAKFGVIFFLWHIVSKVLHLQEITANSTGSREATDFAASHQNFSIVEFIRNKGFYLNNS
  TLLDCEFFGKPCSPKDFAHVFTEYGNCFTFNHGETLQAKRKVSVSGRGLSLLFNVNQEAF
  TDNPALGFVDAGIIFVIHSPKKVPQFDGLGLLSPVGMHARVTIRQVKTVHQEYPWGECNP
  NIKLQNFSSYSTSGCLKECKAQHIKKQCGCVPFLLPGYGIECDLQKYFSCVSPVLDHIEF
  KDLCTVGTHNSSCPVSCEEIEYPATISYSSFPSQKALKYLSKKLNQSRKYIRENLVKIEI
  NYSDLNYKITQQQKAVSVSELLADLGGQLGLFCGASLITIIEIIEYLFTNFYWICIFFLL
  KISEMTQWTPPPQNHLGNKNRIEEC
• Function: Cation channel that gives rise to very low constitutive currents in the absence of activation. The activated channel exhibits selectivity for sodium, and is inhibited by amiloride.
• Tissue Specificity: Detected in small intestine, duodenum and jejunum. Detected at very low levels in testis and rectum.
• KEGG Pathway: Inflammatory mediator regulation of TRP channels (hsa04750)
• Reactome Pathway: Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[1]
Essential hypertension	DIS7WI98	Strong	Biomarker	[2]
High blood pressure	DISY2OHH	Limited	Genetic Variation	[3]
Liddle syndrome	DISY0X0N	Limited	Genetic Variation	[3]
Pelger-Huet anomaly	DISCW4OI	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Acid-sensing ion channel 5 (ASIC5).	[5]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Acid-sensing ion channel 5 (ASIC5).	[6]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Acid-sensing ion channel 5 (ASIC5).	[7]

References

• [1] The TNFalpha receptor TNFRSF1A and genes encoding the amiloride-sensitive sodium channel ENaC as modulators in cystic fibrosis.Hum Genet. 2006 Apr;119(3):331-43. doi: 10.1007/s00439-006-0140-2. Epub 2006 Feb 4.
• [2] Seven lessons from two candidate genes in human essential hypertension: angiotensinogen and epithelial sodium channel.Hypertension. 1999 Jun;33(6):1324-31. doi: 10.1161/01.hyp.33.6.1324.
• [3] Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: a quantitative approach.Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15370-5. doi: 10.1073/pnas.93.26.15370.
• [4] Functional polymorphisms in the mineralocorticoid receptor and amirolide-sensitive sodium channel genes in a patient with sporadic pseudohypoaldosteronism.Hum Genet. 2003 Jan;112(1):91-7. doi: 10.1007/s00439-002-0855-7. Epub 2002 Oct 25.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [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.