Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZX881H)

• DOT Name: Potassium voltage-gated channel subfamily H member 2 (KCNH2)
• Synonyms: Eag homolog; Ether-a-go-go-related gene potassium channel 1; ERG-1; Eag-related protein 1; Ether-a-go-go-related protein 1; H-ERG; hERG-1; hERG1; Voltage-gated potassium channel subunit Kv11.1
• Gene Name: KCNH2
• Related Disease:
  Long QT syndrome
  Long QT syndrome 2
  Short QT syndrome
  Short QT syndrome type 1
  Brugada syndrome
• UniProt ID: KCNH2_HUMAN
• PDB ID: 1BYW; 1UJL; 2L0W; 2L1M; 2L4R; 2LE7; 2N7G; 4HP9; 4HQA; 5VA1; 5VA2; 5VA3; 6SYG
• Pfam ID: PF00027 ; PF00520 ; PF13426
• Sequence:
  MPVRRGHVAPQNTFLDTIIRKFEGQSRKFIIANARVENCAVIYCNDGFCELCGYSRAEVM
  QRPCTCDFLHGPRTQRRAAAQIAQALLGAEERKVEIAFYRKDGSCFLCLVDVVPVKNEDG
  AVIMFILNFEVVMEKDMVGSPAHDTNHRGPPTSWLAPGRAKTFRLKLPALLALTARESSV
  RSGGAGGAGAPGAVVVDVDLTPAAPSSESLALDEVTAMDNHVAGLGPAEERRALVGPGSP
  PRSAPGQLPSPRAHSLNPDASGSSCSLARTRSRESCASVRRASSADDIEAMRAGVLPPPP
  RHASTGAMHPLRSGLLNSTSDSDLVRYRTISKIPQITLNFVDLKGDPFLASPTSDREIIA
  PKIKERTHNVTEKVTQVLSLGADVLPEYKLQAPRIHRWTILHYSPFKAVWDWLILLLVIY
  TAVFTPYSAAFLLKETEEGPPATECGYACQPLAVVDLIVDIMFIVDILINFRTTYVNANE
  EVVSHPGRIAVHYFKGWFLIDMVAAIPFDLLIFGSGSEELIGLLKTARLLRLVRVARKLD
  RYSEYGAAVLFLLMCTFALIAHWLACIWYAIGNMEQPHMDSRIGWLHNLGDQIGKPYNSS
  GLGGPSIKDKYVTALYFTFSSLTSVGFGNVSPNTNSEKIFSICVMLIGSLMYASIFGNVS
  AIIQRLYSGTARYHTQMLRVREFIRFHQIPNPLRQRLEEYFQHAWSYTNGIDMNAVLKGF
  PECLQADICLHLNRSLLQHCKPFRGATKGCLRALAMKFKTTHAPPGDTLVHAGDLLTALY
  FISRGSIEILRGDVVVAILGKNDIFGEPLNLYARPGKSNGDVRALTYCDLHKIHRDDLLE
  VLDMYPEFSDHFWSSLEITFNLRDTNMIPGSPGSTELEGGFSRQRKRKLSFRRRTDKDTE
  QPGEVSALGPGRAGAGPSSRGRPGGPWGESPSSGPSSPESSEDEGPGRSSSPLRLVPFSS
  PRPPGEPPGGEPLMEDCEKSSDTCNPLSGAFSGVSNIFSFWGDSRGRQYQELPRCPAPTP
  SLLNIPLSSPGRRPRGDVESRLDALQRQLNRLETRLSADMATVLQLLQRQMTLVPPAYSA
  VTTPGPGPTSTSPLLPVSPLPTLTLDSLSQVSQFMACEELPPGAPELPQEGPTRRLSLPG
  QLGALTSQPLHRHGSDPGS
• Function: Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr) ; [Isoform A-USO]: Has no channel activity by itself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation; [Isoform B-USO]: Has no channel activity by itself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
• Tissue Specificity: Highly expressed in heart and brain. Isoforms USO are frequently overexpressed in cancer cells.
• Reactome Pathway:
  Phase 3 - rapid repolarisation (R-HSA-5576890)
  Voltage gated Potassium channels (R-HSA-1296072)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Long QT syndrome	DISMKWS3	Definitive	Autosomal dominant	[1]
Long QT syndrome 2	DISQQFTJ	Definitive	Autosomal dominant	[2]
Short QT syndrome	DISOI9X1	Definitive	Autosomal dominant	[1]
Short QT syndrome type 1	DISEKEM0	Definitive	Autosomal dominant	[3]
Brugada syndrome	DISSGN0E	Moderate	Autosomal dominant	[4]

This DOT Affected the Drug Response of 9 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Atenolol	DMNKG1Z	Approved	Potassium voltage-gated channel subfamily H member 2 (KCNH2) increases the Sudden cardiac death ADR of Atenolol.	[50]
Quinidine	DMLPICK	Approved	Potassium voltage-gated channel subfamily H member 2 (KCNH2) decreases the response to substance of Quinidine.	[51]
Carbachol	DMX9K8F	Approved	Potassium voltage-gated channel subfamily H member 2 (KCNH2) affects the response to substance of Carbachol.	[52]
Hydrochlorothiazide	DMUSZHD	Approved	Potassium voltage-gated channel subfamily H member 2 (KCNH2) increases the Sudden cardiac death ADR of Hydrochlorothiazide.	[50]
Procainamide	DMNMXR8	Approved	Potassium voltage-gated channel subfamily H member 2 (KCNH2) increases the Sudden cardiac death ADR of Procainamide.	[50]
Diltiazem	DMAI7ZV	Approved	Potassium voltage-gated channel subfamily H member 2 (KCNH2) increases the Sudden cardiac death ADR of Diltiazem.	[50]
Sotalol	DML60TN	Approved	Potassium voltage-gated channel subfamily H member 2 (KCNH2) increases the Sudden cardiac death ADR of Sotalol.	[50]
Propafenone	DMPIBJK	Approved	Potassium voltage-gated channel subfamily H member 2 (KCNH2) increases the Sudden cardiac death ADR of Propafenone.	[50]
Tocainide	DMYNMDP	Approved	Potassium voltage-gated channel subfamily H member 2 (KCNH2) increases the Sudden cardiac death ADR of Tocainide.	[50]

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 Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[12]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[12]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[13]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone decreases the expression of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[8]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[8]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[15]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[16]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[15]
Sorafenib	DMS8IFC	Approved	Sorafenib decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Fluoxetine	DM3PD2C	Approved	Fluoxetine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[17]
Imatinib	DM7RJXL	Approved	Imatinib decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[18]
Sertraline	DM0FB1J	Approved	Sertraline decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Nefazodone	DM4ZS8M	Approved	Nefazodone decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Lovastatin	DM9OZWQ	Approved	Lovastatin affects the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[20]
Olanzapine	DMPFN6Y	Approved	Olanzapine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[21]
Adenosine triphosphate	DM79F6G	Approved	Adenosine triphosphate decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[22]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[22]
Crizotinib	DM4F29C	Approved	Crizotinib decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[23]
Clotrimazole	DMMFCIH	Approved	Clotrimazole decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Nilotinib	DM7HXWT	Approved	Nilotinib decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[23]
Thioridazine	DM35M8J	Approved	Thioridazine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[16]
Propranolol	DM79NTF	Approved	Propranolol decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[25]
Imipramine	DM2NUH3	Approved	Imipramine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Vandetanib	DMRICNP	Approved	Vandetanib decreases the expression of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[18]
Carvedilol	DMHTEAO	Approved	Carvedilol decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[26]
Erythromycin	DM4K7GQ	Approved	Erythromycin decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Loratadine	DMF3AN7	Approved	Loratadine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[27]
Pentamidine	DMHZJCG	Approved	Pentamidine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[15]
Flecainide	DMSQDLE	Approved	Flecainide decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Reserpine	DM6VM38	Approved	Reserpine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[28]
Lidocaine	DML4ZOT	Approved	Lidocaine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Tolcapone	DM8MNVO	Approved	Tolcapone decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Lamotrigine	DM8SXYG	Approved	Lamotrigine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[29]
Terbinafine	DMI6HUW	Approved	Terbinafine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Dronedarone	DMA8FS5	Approved	Dronedarone decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[30]
Dobutamine	DMD1B8Z	Approved	Dobutamine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Dutasteride	DMQ4TJK	Approved	Dutasteride decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Fexofenadine	DM17ONX	Approved	Fexofenadine increases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[32]
Gabapentin	DM6T924	Approved	Gabapentin decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[29]
Glibenclamide	DM8JXPZ	Approved	Glibenclamide decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Trazodone	DMK1GBJ	Approved	Trazodone decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[33]
Miconazole	DMPMYE8	Approved	Miconazole decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Dipyridamole	DMXY30O	Approved	Dipyridamole decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[34]
Metoprolol	DMOJ0V6	Approved	Metoprolol decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[25]
Digoxin	DMQCTIH	Approved	Digoxin decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[35]
Methadone	DMTW6IU	Approved	Methadone decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[36]
Clarithromycin	DM4M1SG	Approved	Clarithromycin decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Phentolamine	DMXYJOB	Approved	Phentolamine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Aripiprazole	DM3NUMH	Approved	Aripiprazole decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Desloratadine	DM56YN7	Approved	Desloratadine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Topiramate	DM82Z30	Approved	Topiramate decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[29]
Fentanyl	DM8WAHT	Approved	Fentanyl decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Quinine	DMSWYF5	Approved	Quinine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[37]
Desipramine	DMT2FDC	Approved	Desipramine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[38]
Dextromethorphan	DMUDJZM	Approved	Dextromethorphan decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[39]
Romiplostim	DM3U7SZ	Approved	Romiplostim decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Tacrine	DM51FY6	Approved	Tacrine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Metoclopramide	DMFA5MY	Approved	Metoclopramide decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[40]
Domperidone	DMBDPY0	Approved	Domperidone decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[40]
Disopyramide	DM5SYZP	Approved	Disopyramide decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[41]
Paliperidone	DM7NPJS	Approved	Paliperidone decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[42]
Luvox	DMJKROX	Approved	Luvox decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Idarubicin	DMM0XGL	Approved	Idarubicin decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Alpidem	DMN7Y9K	Approved	Alpidem decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Salmeterol	DMIEU69	Approved	Salmeterol decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Hydroxyzine	DMF8Y74	Approved	Hydroxyzine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[43]
Oxybuprocaine	DMI0GDH	Approved	Oxybuprocaine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Amantadine	DMS3YE9	Approved	Amantadine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[15]
Cisapride	DMY7PED	Approved	Cisapride decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[44]
Bepridil	DM0RKS4	Approved	Bepridil decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[16]
Chlorpheniramine	DM5URA2	Approved	Chlorpheniramine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[45]
Duloxetine	DM9BI7M	Approved	Duloxetine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Pentobarbital	DMFNH7L	Approved	Pentobarbital decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[46]
Retigabine	DMGNYIH	Approved	Retigabine affects the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[47]
Tazarotene	DM8SMD1	Approved	Tazarotene decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Cepharanthine	DM9Y5JB	Approved	Cepharanthine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Ziprasidone	DMM58JY	Approved	Ziprasidone decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Arformoterol	DMYM974	Approved	Arformoterol decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Dofetilide	DMPN1TW	Approved	Dofetilide decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[48]
Flupentixol	DM0DJ9O	Approved	Flupentixol decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Mepyramine	DMB4SFH	Approved	Mepyramine affects the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[20]
Droperidol	DM0DXA8	Approved	Droperidol decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[49]
Dantrolene	DM1D8XY	Approved	Dantrolene decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[19]
Aprindine	DMBXWU8	Approved	Aprindine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Proflavine	DMF1X5P	Approved	Proflavine decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[14]
Econazole	DMFSWGH	Approved	Econazole decreases the activity of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[28]

5 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR affects the binding of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[24]
Perhexiline	DMINO7Z	Approved	Perhexiline affects the binding of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[31]
Ofloxacin	DM0VQN3	Approved	Ofloxacin affects the binding of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[24]
Norfloxacin	DMIZ6W2	Approved	Norfloxacin affects the binding of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[24]
Pefloxacin	DM49IGF	Approved	Pefloxacin affects the binding of Potassium voltage-gated channel subfamily H member 2 (KCNH2).	[24]

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