Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZNQUW9)

• DOT Name: Potassium voltage-gated channel subfamily E member 1 (KCNE1)
• Synonyms: Delayed rectifier potassium channel subunit IsK; IKs producing slow voltage-gated potassium channel subunit beta Mink; Minimal potassium channel
• Gene Name: KCNE1
• Related Disease:
  Long QT syndrome 5
  Myocardial infarction
  Advanced cancer
  Arrhythmia
  Astrocytoma
  Atrial fibrillation
  Cardiac arrest
  Cardiac disease
  Cardiac failure
  Cardiovascular disease
  Congestive heart failure
  Convulsion
  Deafness
  Endometrial cancer
  Endometrial carcinoma
  Jervell and Lange-Nielsen syndrome 1
  Jervell and Lange-Nielsen syndrome 2
  Long QT syndrome 1
  Meniere disease
  Propionic acidemia
  Short QT syndrome
  Silver-Russell syndrome
  Ventricular tachycardia
  Visceral heterotaxy
  Amelogenesis imperfecta type 1G
  Sensorineural hearing loss disorder
  Obsolete Jervell and Lange-Nielsen syndrome
  Andersen-Tawil syndrome
  Brugada syndrome
  Catecholaminergic polymorphic ventricular tachycardia 1
  Hyperaldosteronism
  Jervell and Lange-Nielsen syndrome
  Nephropathy
  Temporal lobe epilepsy
  Type-1 diabetes
  Type-1/2 diabetes
• UniProt ID: KCNE1_HUMAN
• PDB ID: 2K21
• Pfam ID: PF02060
• Sequence:
  MILSNTTAVTPFLTKLWQETVQQGGNMSGLARRSPRSSDGKLEALYVLMVLGFFGFFTLG
  IMLSYIRSKKLEHSNDPFNVYIESDAWQEKDKAYVQARVLESYRSCYVVENHLAIEQPNT
  HLPETKPSP
• Function: Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1. Assembled with KCNQ1/KVLQT1 is proposed to form the slowly activating delayed rectifier cardiac potassium (IKs) channel. The outward current reaches its steady state only after 50 seconds. Assembled with KCNH2/HERG may modulate the rapidly activating component of the delayed rectifying potassium current in heart (IKr).
• Tissue Specificity: Expressed in lung, kidney, testis, ovaries, small intestine, peripheral blood leukocytes. Expressed in the heart . Not detected in pancreas, spleen, prostate and colon. Restrictively localized in the apical membrane portion of epithelial cells.
• KEGG Pathway: Adrenergic sig.ling in cardiomyocytes (hsa04261)
• Reactome Pathway:
  Phase 2 - plateau phase (R-HSA-5576893)
  Phase 3 - rapid repolarisation (R-HSA-5576890)

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Long QT syndrome 5	DISTN36Q	Definitive	Autosomal dominant	[1]
Myocardial infarction	DIS655KI	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Arrhythmia	DISFF2NI	Strong	Genetic Variation	[4]
Astrocytoma	DISL3V18	Strong	Altered Expression	[5]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[6]
Cardiac arrest	DIS9DIA4	Strong	Genetic Variation	[7]
Cardiac disease	DISVO1I5	Strong	Genetic Variation	[8]
Cardiac failure	DISDC067	Strong	Genetic Variation	[9]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[10]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[9]
Convulsion	DIS1CYA2	Strong	Genetic Variation	[6]
Deafness	DISKCLH4	Strong	Biomarker	[11]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[12]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[12]
Jervell and Lange-Nielsen syndrome 1	DISVWU3A	Strong	Biomarker	[13]
Jervell and Lange-Nielsen syndrome 2	DIS75N4V	Strong	Autosomal recessive	[14]
Long QT syndrome 1	DISXK5OU	Strong	Genetic Variation	[4]
Meniere disease	DISC5R5F	Strong	Genetic Variation	[15]
Propionic acidemia	DIS56N48	Strong	Biomarker	[11]
Short QT syndrome	DISOI9X1	Strong	Biomarker	[16]
Silver-Russell syndrome	DISSVJ1D	Strong	Genetic Variation	[17]
Ventricular tachycardia	DISIBXJ3	Strong	Genetic Variation	[18]
Visceral heterotaxy	DIS1DV90	Strong	Genetic Variation	[19]
Amelogenesis imperfecta type 1G	DISS8U5Q	moderate	Genetic Variation	[20]
Sensorineural hearing loss disorder	DISJV45Z	moderate	Genetic Variation	[21]
Obsolete Jervell and Lange-Nielsen syndrome	DISRHOUU	Supportive	Autosomal recessive	[22]
Andersen-Tawil syndrome	DIS3IWZ7	Limited	Biomarker	[23]
Brugada syndrome	DISSGN0E	Limited	Biomarker	[24]
Catecholaminergic polymorphic ventricular tachycardia 1	DISKGB3F	Limited	Biomarker	[25]
Hyperaldosteronism	DIS3WGAL	Limited	Biomarker	[26]
Jervell and Lange-Nielsen syndrome	DISGCX89	Limited	Biomarker	[4]
Nephropathy	DISXWP4P	Limited	Genetic Variation	[15]
Temporal lobe epilepsy	DISNOPXX	Limited	Altered Expression	[27]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[28]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[29]

This DOT Affected the Drug Response of 12 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Propranolol	DM79NTF	Approved	Potassium voltage-gated channel subfamily E member 1 (KCNE1) increases the Sudden cardiac death ADR of Propranolol.	[36]
Atenolol	DMNKG1Z	Approved	Potassium voltage-gated channel subfamily E member 1 (KCNE1) increases the Sudden cardiac death ADR of Atenolol.	[36]
Quinidine	DMLPICK	Approved	Potassium voltage-gated channel subfamily E member 1 (KCNE1) increases the Sudden cardiac death ADR of Quinidine.	[36]
Flecainide	DMSQDLE	Approved	Potassium voltage-gated channel subfamily E member 1 (KCNE1) increases the Sudden cardiac death ADR of Flecainide.	[36]
Procainamide	DMNMXR8	Approved	Potassium voltage-gated channel subfamily E member 1 (KCNE1) increases the Sudden cardiac death ADR of Procainamide.	[36]
Diltiazem	DMAI7ZV	Approved	Potassium voltage-gated channel subfamily E member 1 (KCNE1) increases the Sudden cardiac death ADR of Diltiazem.	[36]
Sotalol	DML60TN	Approved	Potassium voltage-gated channel subfamily E member 1 (KCNE1) increases the Sudden cardiac death ADR of Sotalol.	[36]
Propafenone	DMPIBJK	Approved	Potassium voltage-gated channel subfamily E member 1 (KCNE1) increases the Sudden cardiac death ADR of Propafenone.	[36]
Dofetilide	DMPN1TW	Approved	Potassium voltage-gated channel subfamily E member 1 (KCNE1) increases the Sudden cardiac death ADR of Dofetilide.	[36]
Tocainide	DMYNMDP	Approved	Potassium voltage-gated channel subfamily E member 1 (KCNE1) increases the Sudden cardiac death ADR of Tocainide.	[36]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Potassium voltage-gated channel subfamily E member 1 (KCNE1) increases the Sudden cardiac death ADR of Amiodarone.	[36]
Verapamil	DMA7PEW	Phase 2/3 Trial	Potassium voltage-gated channel subfamily E member 1 (KCNE1) increases the Sudden cardiac death ADR of Verapamil.	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Potassium voltage-gated channel subfamily E member 1 (KCNE1).	[30]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Potassium voltage-gated channel subfamily E member 1 (KCNE1).	[31]
Pentobarbital	DMFNH7L	Approved	Pentobarbital decreases the activity of Potassium voltage-gated channel subfamily E member 1 (KCNE1).	[32]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Potassium voltage-gated channel subfamily E member 1 (KCNE1).	[34]
Ginsenoside Re	DM46FVD	Investigative	Ginsenoside Re increases the expression of Potassium voltage-gated channel subfamily E member 1 (KCNE1).	[35]
Ginsenoside Rb1	DMF70AB	Investigative	Ginsenoside Rb1 increases the expression of Potassium voltage-gated channel subfamily E member 1 (KCNE1).	[35]

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 E member 1 (KCNE1).	[33]

References

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