General Information of Drug Transporter (DT)
DT ID	DTD0510 Transporter Info
Gene Name	KCNH2
Protein Name	Voltage-gated potassium channel Kv11.1
Gene ID	3757
UniProt ID	Q12809
Genetic Polymorphisms of DT (GPD)
Genetic Polymorphism	rs1137617
Site of GPD	chr7:150951110 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	A>C / A>G / A>T
Minor Allele Frequency	A=0.2278/1141 (Global)
Genotype GG	Click to Show/Hide the Full List of Affected Drugs:         12 Drugs in Total
Candesartan	Drug Info	Essential hypertension	Irrelevant to the drug response in patients (compare with genotypes AA + AG)		[ 1]
Irbesartan	Drug Info	Essential hypertension	Irrelevant to the drug response in patients (compare with genotypes AA + AG)		[ 1]
Candesartan	N.A.	Torsades De Pointes	Genotype GG is not associated with response to candesartan, imidapril or irbesartan in people with Essential hypertension as compared to genotypes AA + AG.		[ 1]
Imidapril	N.A.	Torsades De Pointes	Genotype GG is not associated with response to candesartan, imidapril or irbesartan in people with Essential hypertension as compared to genotypes AA + AG.		[ 1]
Irbesartan	N.A.	Torsades De Pointes	Genotype GG is not associated with response to candesartan, imidapril or irbesartan in people with Essential hypertension as compared to genotypes AA + AG.		[ 1]
Atenolol	N.A.	Torsades De Pointes	Genotype GG is associated with response to atenolol, bisoprolol, Celiprolol or doxazosin in people with Essential hypertension as compared to genotypes AA + AG.		[ 1]
Bisoprolol	N.A.	Torsades De Pointes	Genotype GG is associated with response to atenolol, bisoprolol, Celiprolol or doxazosin in people with Essential hypertension as compared to genotypes AA + AG.		[ 1]
Celiprolol	N.A.	Torsades De Pointes	Genotype GG is associated with response to atenolol, bisoprolol, Celiprolol or doxazosin in people with Essential hypertension as compared to genotypes AA + AG.		[ 1]
Doxazosin	N.A.	Torsades De Pointes	Genotype GG is associated with response to atenolol, bisoprolol, Celiprolol or doxazosin in people with Essential hypertension as compared to genotypes AA + AG.		[ 1]
Calcium Channel Blockers	N.A.	Essential Hypertension	Patients with the GG genotype with essential hypertension who are treated with calcium channel blockers may have smaller reductions in diastolic blood pressure and mean arterial pressure as compared to patients with the AA or AG genotype. Other genetic and clinical factors may also influence a patient's response to antihypertensive treatments.		[ 1]
Nitrendipine	N.A.	Essential Hypertension	Patients with the GG genotype with essential hypertension who are treated with calcium channel blockers may have smaller reductions in diastolic blood pressure and mean arterial pressure as compared to patients with the AA or AG genotype. Other genetic and clinical factors may also influence a patient's response to antihypertensive treatments.		[ 1]
Imidapril	N.A.	Essential hypertension	Irrelevant to the drug response in patients (compare with genotypes AA + AG)		[ 1]
Genotypes AA + AG	Click to Show/Hide the Full List of Affected Drugs:           4 Drugs in Total
Calcium Channel Blockers	N.A.	Torsades De Pointes	Genotypes AA + AG are associated with increased reduction in blood pressure when treated with calcium channel blockers or nitrendipine in people with Essential hypertension as compared to genotype GG.		[ 1]
Nitrendipine	N.A.	Torsades De Pointes	Genotypes AA + AG are associated with increased reduction in blood pressure when treated with calcium channel blockers or nitrendipine in people with Essential hypertension as compared to genotype GG.		[ 1]
Calcium Channel Blockers	N.A.	Essential Hypertension	Genotypes AA + AG are associated with increased reduction in blood pressure when treated with calcium channel blockers or nitrendipine in people with Essential hypertension as compared to genotype GG.		[ 1]
Nitrendipine	N.A.	Essential Hypertension	Genotypes AA + AG are associated with increased reduction in blood pressure when treated with calcium channel blockers or nitrendipine in people with Essential hypertension as compared to genotype GG.		[ 1]
Genotype AA	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Calcium Channel Blockers	N.A.	Essential Hypertension	Patients with the AA genotype with essential hypertension who are treated with calcium channel blockers may have greater reductions in diastolic blood pressure and mean arterial pressure as compared to patients with the GG genotype. Male patients with the AA genotype may also have greater reductions in systolic blood pressure. Other genetic and clinical factors may also influence a patient's response to antihypertensive treatments.		[ 1]
Nitrendipine	N.A.	Essential Hypertension	Patients with the AA genotype with essential hypertension who are treated with calcium channel blockers may have greater reductions in diastolic blood pressure and mean arterial pressure as compared to patients with the GG genotype. Male patients with the AA genotype may also have greater reductions in systolic blood pressure. Other genetic and clinical factors may also influence a patient's response to antihypertensive treatments.		[ 1]
Genotype AG	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Calcium Channel Blockers	N.A.	Essential Hypertension	Patients with the AG genotype with essential hypertension who are treated with calcium channel blockers may have greater reductions in diastolic blood pressure and mean arterial pressure as compared to patients with the GG genotype. Male patients with the AG genotype may also have greater reductions in systolic blood pressure. Other genetic and clinical factors may also influence a patient's response to antihypertensive treatments.		[ 1]
Nitrendipine	N.A.	Essential Hypertension	Patients with the AG genotype with essential hypertension who are treated with calcium channel blockers may have greater reductions in diastolic blood pressure and mean arterial pressure as compared to patients with the GG genotype. Male patients with the AG genotype may also have greater reductions in systolic blood pressure. Other genetic and clinical factors may also influence a patient's response to antihypertensive treatments.		[ 1]
Genetic Polymorphism	rs36210421
Site of GPD	chr7:150947340 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	C>A / C>T
Minor Allele Frequency	C=0.9920/1963 (Global)
Allele A	Click to Show/Hide the Full List of Affected Drugs:           3 Drugs in Total
Cisapride	N.A.	Cardiotoxicity	Allele A is not associated with increased sensitivity to cisapride as compared to allele C.		[ 2]
Dofetilide	N.A.	Cardiotoxicity	Allele A is associated with decreased catalytic activity of KCNH2 when exposed to dofetilide HEK293.		[ 3]
Dofetilide	N.A.	Torsades De Pointes	Allele A is associated with Torsades de Pointes when treated with dofetilide.		[ 3]
Genetic Polymorphism	rs1805123
Site of GPD	chr7:150948446 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	T>A / T>C / T>G
Minor Allele Frequency	T=0.8680/1717 (Global)
Allele G	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Cisapride	N.A.	Cardiotoxicity	Allele G is not associated with increased sensitivity to cisapride as compared to allele T.		[ 2]
Antiarrhythmics, Class I And Iii	N.A.	Acquired Long Qt Syndrome (alqts)	Allele G is not associated with risk of Acquired Long QT Syndrome (aLQTS) when treated with antiarrhythmics, class i and iii.		[ 5]
Genetic Polymorphism	rs199472959
Site of GPD	chr7:150951502 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	A>C
Allele C	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Quinidine	N.A.	Cardiotoxicity	Allele C is associated with decreased inhibition of KCNH2 due to quinidine as compared to allele A.		[ 5]
Genetic Polymorphism	rs12720441
Site of GPD	chr7:150950216 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	G>A / G>C
Minor Allele Frequency	G=1.0000/1979 (Global)
Allele A	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Amiodarone	N.A.	Torsades De Pointes	Allele A is associated with increased risk of Torsades de Pointes when treated with amiodarone as compared to allele G.		[ 4]
Genotype AA	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Amiodarone	N.A.	Torsades De Pointes	Patients with the AA genotype may have increased risk for Torsades de Point when treated with amiodarone as compared to patients with the GG genotype. Other genetic and clinical factors may also influence a patient's risk for adverse events.		[ 4]
Genotype AG	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Amiodarone	N.A.	Torsades De Pointes	Patients with the AG genotype may have increased risk for Torsades de Point when treated with amiodarone as compared to patients with the GG genotype. Other genetic and clinical factors may also influence a patient's risk for adverse events.		[ 4]
Genotype GG	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Amiodarone	N.A.	Torsades De Pointes	Patients with the GG genotype may have decreased risk for Torsades de Point when treated with amiodarone as compared to patients with the AA or AG genotype. Patients with the GG genotype may still be at risk for adverse events when taking amiodarone based on their genotype. Other genetic and clinical factors may also influence a patient's risk for adverse events.		[ 4]
Genetic Polymorphism	rs104894021
Site of GPD	chr7:150951629 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	G>T
Allele T	Click to Show/Hide the Full List of Affected Drugs:           4 Drugs in Total
Quinidine	N.A.	Acquired Long Qt Syndrome (alqts)	Allele T is associated with decreased inhibition of KCNH2 when exposed to quinidine as compared to allele G.		[ 6]
Disopyramide	N.A.	Acquired Long Qt Syndrome (alqts)	Allele T is associated with decreased inhibition of KCNH2 when exposed to disopyramide as compared to allele G.		[ 6]
Disopyramide	N.A.	Short Qt Syndrome 1	Allele T is associated with decreased inhibition of KCNH2 when exposed to disopyramide as compared to allele G.		[ 6]
Quinidine	N.A.	Short Qt Syndrome 1	Allele T is associated with decreased inhibition of KCNH2 when exposed to quinidine as compared to allele G.		[ 6]
Allele C	Click to Show/Hide the Full List of Affected Drugs:           4 Drugs in Total
Disopyramide	N.A.	Acquired Long Qt Syndrome (alqts)	Allele C is associated with decreased inhibition of KCNH2 when exposed to disopyramide as compared to allele G.		[ 6]
Quinidine	N.A.	Acquired Long Qt Syndrome (alqts)	Allele C is associated with decreased inhibition of KCNH2 when exposed to quinidine as compared to allele G.		[ 6]
Disopyramide	N.A.	Short Qt Syndrome 1	Allele C is associated with decreased inhibition of KCNH2 when exposed to disopyramide as compared to allele G.		[ 6]
Quinidine	N.A.	Short Qt Syndrome 1	Allele C is associated with decreased inhibition of KCNH2 when exposed to quinidine as compared to allele G.		[ 6]
Genotype CC	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Disopyramide	N.A.	Short Qt Syndrome 1	Patients with the CC genotype may experience decreased inhibition of KCNH2 by disopyramide as compared to patients with the GG genotype. However, this decrease in inhibition is not considered to be clinically significant. Other genetic and clinical factors may also affect inhibition of KCNH2 by disopyramide.		[ 6]
Quinidine	N.A.	Short Qt Syndrome 1	Patients with the CC genotype may experience decreased inhibition of KCNH2 by quinidine as compared to patients the GG genotype. Other genetic and clinical factors may also affect inhibition of KCNH2 by quinidine.		[ 6]
Genotype CG	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Disopyramide	N.A.	Short Qt Syndrome 1	Patients with the CG genotype may experience decreased inhibition of KCNH2 by disopyramide as compared to patients with the GG genotype. However, this decrease in inhibition is not considered to be clinically significant. Other genetic and clinical factors may also affect inhibition of KCNH2 by disopyramide.		[ 6]
Quinidine	N.A.	Short Qt Syndrome 1	Patients with the CG genotype may experience decreased inhibition of KCNH2 by quinidine as compared to patients the GG genotype. Other genetic and clinical factors may also affect inhibition of KCNH2 by quinidine.		[ 6]
Genotype CT	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Disopyramide	N.A.	Short Qt Syndrome 1	Patients with the CT genotype may experience decreased inhibition of KCNH2 by disopyramide as compared to patients with the GG genotype. However, this decrease in inhibition is not considered to be clinically significant. Other genetic and clinical factors may also affect inhibition of KCNH2 by disopyramide.		[ 6]
Quinidine	N.A.	Short Qt Syndrome 1	Patients with the CT genotype may experience decreased inhibition of KCNH2 by quinidine as compared to patients the GG genotype. Other genetic and clinical factors may also affect inhibition of KCNH2 by quinidine.		[ 6]
Genotype GG	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Disopyramide	N.A.	Short Qt Syndrome 1	Patients with the GG genotype may experience increased inhibition of KCNH2 by disopyramide as compared to patients carrying at least one C or T allele. Other genetic and clinical factors may also affect inhibition of KCNH2 by disopyramide.		[ 6]
Quinidine	N.A.	Short Qt Syndrome 1	Patients with the GG genotype may experience increased inhibition of KCNH2 by quinidine as compared to patients carrying at least one C or T allele. Other genetic and clinical factors may also affect inhibition of KCNH2 by quinidine.		[ 6]
Genotype GT	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Disopyramide	N.A.	Short Qt Syndrome 1	Patients with the GT genotype may experience decreased inhibition of KCNH2 by disopyramide as compared to patients with the GG genotype. However, this decrease in inhibition is not considered to be clinically significant. Other genetic and clinical factors may also affect inhibition of KCNH2 by disopyramide.		[ 6]
Quinidine	N.A.	Short Qt Syndrome 1	Patients with the GT genotype may experience decreased inhibition of KCNH2 by quinidine as compared to patients the GG genotype. Other genetic and clinical factors may also affect inhibition of KCNH2 by quinidine.		[ 6]
Genotype TT	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Disopyramide	N.A.	Short Qt Syndrome 1	Patients with the TT genotype may experience decreased inhibition of KCNH2 by disopyramide as compared to patients with the GG genotype. However, this decrease in inhibition is not considered to be clinically significant. Other genetic and clinical factors may also affect inhibition of KCNH2 by disopyramide.		[ 6]
Quinidine	N.A.	Short Qt Syndrome 1	Patients with the TT genotype may experience decreased inhibition of KCNH2 by quinidine as compared to patients the GG genotype. Other genetic and clinical factors may also affect inhibition of KCNH2 by quinidine.		[ 6]
Genetic Polymorphism	rs138776684
Site of GPD	chr7:150957380 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	G>A
Minor Allele Frequency	G=0.9990/1977 (Global)
Allele A	Click to Show/Hide the Full List of Affected Drugs:           4 Drugs in Total
Cisapride	N.A.	Acquired Long Qt Syndrome (alqts)	Allele A is associated with increased likelihood of Acquired Long QT Syndrome (aLQTS) and Torsades de Pointes when treated with cisapride and clarithromycin in people with Acquired Long QT Syndrome (aLQTS) as compared to allele G.		[ 7]
Cisapride	N.A.	Torsades De Pointes	Allele A is associated with increased likelihood of Acquired Long QT Syndrome (aLQTS) and Torsades de Pointes when treated with cisapride and clarithromycin in people with Acquired Long QT Syndrome (aLQTS) as compared to allele G.		[ 7]
Clarithromycin	N.A.	Acquired Long Qt Syndrome (alqts)	Allele A is associated with increased likelihood of Acquired Long QT Syndrome (aLQTS) and Torsades de Pointes when treated with cisapride and clarithromycin in people with Acquired Long QT Syndrome (aLQTS) as compared to allele G.		[ 7]
Clarithromycin	N.A.	Torsades De Pointes	Allele A is associated with increased likelihood of Acquired Long QT Syndrome (aLQTS) and Torsades de Pointes when treated with cisapride and clarithromycin in people with Acquired Long QT Syndrome (aLQTS) as compared to allele G.		[ 7]
Genetic Polymorphism	rs199472944
Site of GPD	chr7:150951552 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	G>A
Genotype AG	Click to Show/Hide the Full List of Affected Drugs:           3 Drugs in Total
Hydroxyzine	N.A.	Acquired Long Qt Syndrome (alqts)	Genotype AG is associated with increased likelihood of Acquired Long QT Syndrome (aLQTS), Syncope and Torsades de Pointes when treated with hydroxyzine in women as compared to genotype GG.		[ 8]
Hydroxyzine	N.A.	Syncope	Genotype AG is associated with increased likelihood of Acquired Long QT Syndrome (aLQTS), Syncope and Torsades de Pointes when treated with hydroxyzine in women as compared to genotype GG.		[ 8]
Hydroxyzine	N.A.	Torsades De Pointes	Genotype AG is associated with increased likelihood of Acquired Long QT Syndrome (aLQTS), Syncope and Torsades de Pointes when treated with hydroxyzine in women as compared to genotype GG.		[ 8]
Genetic Polymorphism	rs3807372
Site of GPD	chr7:150971969 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	G>A / G>T
Minor Allele Frequency	G=0.7100/1405 (Global)
Genotype AA	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Escitalopram	N.A.	Acquired Long Qt Syndrome (alqts)	Genotype AA is associated with increased likelihood of Acquired Long QT Syndrome (aLQTS) when treated with escitalopram as compared to genotypes AG + GG.		[ 9]
References
1	The KCNH2 genetic polymorphism (1956, C>T) is a novel biomarker that is associated with CCB and ,-ADR blocker response in EH patients in China. 2013 Apr 22;8(4):e61317.
2	Molecular and functional characterization of common polymorphisms in HERG (KCNH2) potassium channels. Am J Physiol Heart Circ Physiol. 2004 Jun;286(6):H2434-41.
3	Role of a KCNH2 polymorphism (R1047 L) in dofetilide-induced Torsades de Pointes. J Mol Cell Cardiol. 2004 Nov;37(5):1031-9.
4	Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. Circulation. 2002 Apr 23;105(16):1943-8.
5	Action potential clamp characterization of the S631A hERG mutation associated with short QT syndrome. Physiol Rep. 2018 Sep;6(17):e13845.
6	Disopyramide is an effective inhibitor of mutant HERG K+ channels involved in variant 1 short QT syndrome. J Mol Cell Cardiol. 2006 Sep;41(3):563-6.
7	Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J Mol Med (Berl). 2004 Mar;82(3):182-8.
8	Hydroxyzine, a first generation H(1)-receptor antagonist, inhibits human ether-a-go-go-related gene (HERG) current and causes syncope in a patient with the HERG mutation. J Pharmacol Sci. 2008 Dec;108(4):462-71.
9	Escitalopram-induced QTc prolongation and its relationship with KCNQ1, KCNE1, and KCNH2 gene polymorphisms. J Affect Disord. 2024 Feb 15;347:399-405.

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