Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD8GEO0)

• DOT Name: Potassium voltage-gated channel subfamily S member 1 (KCNS1)
• Synonyms: Delayed-rectifier K(+) channel alpha subunit 1; Voltage-gated potassium channel subunit Kv9.1
• Gene Name: KCNS1
• Related Disease:
  Neuralgia
  Peripheral sensory neuropathies
  Anxiety
  Anxiety disorder
• UniProt ID: KCNS1_HUMAN
• Pfam ID: PF02214 ; PF00520
• Sequence:
  MLMLLVRGTHYENLRSKVVLPTPLGGRSTETFVSEFPGPDTGIRWRRSDEALRVNVGGVR
  RQLSARALARFPGTRLGRLQAAASEEQARRLCDDYDEAAREFYFDRHPGFFLSLLHFYRT
  GHLHVLDELCVFAFGQEADYWGLGENALAACCRARYLERRLTQPHAWDEDSDTPSSVDPC
  PDEISDVQRELARYGAARCGRLRRRLWLTMENPGYSLPSKLFSCVSISVVLASIAAMCIH
  SLPEYQAREAAAAVAAVAAGRSPEGVRDDPVLRRLEYFCIAWFSFEVSSRLLLAPSTRNF
  FCHPLNLIDIVSVLPFYLTLLAGVALGDQGGKEFGHLGKVVQVFRLMRIFRVLKLARHST
  GLRSLGATLKHSYREVGILLLYLAVGVSVFSGVAYTAEKEEDVGFNTIPACWWWGTVSMT
  TVGYGDVVPVTVAGKLAASGCILGGILVVALPITIIFNKFSHFYRRQKALEAAVRNSNHQ
  EFEDLLSSIDGVSEASLETSRETSQEGQSADLESQAPSEPPHPQMY
• Function: Potassium channel subunit that does not form functional channels by itself. Can form functional heterotetrameric channels with KCNB1 and KCNB2; modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1 and KCNB2.
• Tissue Specificity: Detected in all tissues tested with the exception of skeletal muscle. Highly expressed in adult and fetal brain, fetal kidney and lung, and adult prostate and testis .
• Reactome Pathway: Voltage gated Potassium channels (R-HSA-1296072)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuralgia	DISWO58J	Strong	Biomarker	[1]
Peripheral sensory neuropathies	DISYWI6M	moderate	Biomarker	[2]
Anxiety	DISIJDBA	Limited	Biomarker	[3]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Potassium voltage-gated channel subfamily S member 1 (KCNS1).	[4]

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 increases the methylation of Potassium voltage-gated channel subfamily S member 1 (KCNS1).	[5]

References

• [1] Mice lacking Kcns1 in peripheral neurons show increased basal and neuropathic pain sensitivity.Pain. 2018 Aug;159(8):1641-1651. doi: 10.1097/j.pain.0000000000001255.
• [2] KCNS1, but not GCH1, is associated with pain intensity in a black southern African population with HIV-associated sensory neuropathy: a genetic association study.J Acquir Immune Defic Syndr. 2013 May 1;63(1):27-30. doi: 10.1097/QAI.0b013e318285cf36.
• [3] Biopsychosocial influence on exercise-induced injury: genetic and psychological combinations are predictive of shoulder pain phenotypes.J Pain. 2014 Jan;15(1):68-80. doi: 10.1016/j.jpain.2013.09.012. Epub 2013 Oct 5.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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.