Gene mutations in cardiac arrhythmias: a review of recent evidence in ion channelopathies

Figures & data

Table 1 Inherited arrhythmogenic disorders

Mutations in genes encoding developmental components of the heart

Hypertrophic cardiomyopathy (HCM)

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)

Dilated cardiomyopathy (DC)

Mutations in genes encoding functional units of ion channels and/or transporter-associated proteins (“ion channelopathies”)

Congenital long-QT syndrome (LQTS)

Brugada syndrome (BrS)

Catecholaminergic polymorphic ventricular tachycardia (CPVT)

Short-QT syndrome (SQTS)

Table 2 Congenital long-QT syndrome (LQTS)

Name	Current	Gain/loss of function	Protein	Gene	Reference
LQT1	IKs	Loss	KvLQT1	KCNQ1	Wang et al^Citation3
LQT2	IKr	Loss	Kv11.1	KCNH2	Curran et al^Citation2
LQT3	INa	Gain	Nav1.5	SCN5A	Wang et al^Citation4
LQT4	INCX, INaK, InsP3R	Loss	Ankyrin-B	ANKB	Mohler et al^Citation9
LQT5	IKs	Loss	MinK	KCNE1	Splawski et al^Citation93
LQT6	IKr	Loss	MiRP1	KCNE2	Abbott et al^Citation94
LQT7	IK1	Loss	Kir2.1	KCNJ2	Plaster et al,^Citation16 Ai et al^Citation95
LQT8	ICa,L	Gain	Cav1.2α1	CACNA1C	Splawski et al^Citation25
LQT9	INa	Gain	Caveolin-3	CAV3	Vatta et al,^Citation10 Ye et al^Citation96
LQT10	INa	Gain	Navβ4	SCN4B	Domingo et al,^Citation97 Medeiros-Domingo et al^Citation98
LQT11	IKs	Loss	Yotiao	AKAP9	Chen et al^Citation13
LQT12	INa	Gain	α-1 Syntrophin	SNTA1	Ueda et al,^Citation99 Wu et al^Citation100
LQT13	IK-Ach	Loss	Kir3.4	KCNJ5	Yang et al^Citation101

Abbreviations: I_Kr and I_Ks, rapid and slow delayed-rectifier potassium currents respectively; I_Na, sodium current; I_NCX, Na⁺/Ca²⁺ exchanger current; I_NaK, Na⁺/K⁺ ATPase (pump) current; InsP₃R, inositol 1,4,5-trisphosphate (IP3) receptors; I_K1, inward-rectifier potassium current; I_Ca,L, L-type calcium current; I_K-Ach, acetylcholine-regulated potassium current.

Table 3 Brugada syndrome (BrS)

Name	Current	Gain/loss of function	Protein	Gene	Reference
BrS1	INa	Loss	Nav1.5	SCN5A	Chen et al,^Citation54 Kapplinger et al,^Citation102 Schulze-Bahr et al^Citation103
BrS2	INa	Loss		GPD1-L	London et al^Citation56
BrS3	ICa,L	Loss	Cav1.2α1	CACNA1C	Antzelevitch et al^Citation58
BrS4	ICa,L	Loss	Cavβ2b	CACNB2b	Antzelevitch et al^Citation58
BrS5	INa	Loss	Navβ1	SCN1B	Watanabe et al^Citation5
BrS6	Ito	Gain	MiRP2	KCNE3	Delpón et al^Citation60
BrS7	INa	Loss	Navβ3	SCN3B	Hu et al^Citation55
BrS8	IK-ATP	Gain	Kir6.1	KCNJ8	Medeiros-Domingo et al^Citation104
BrS9	ICa,L	Loss	Cavα2d	CACNA2D1	Burashnikov et al^Citation59
BrS10	Ito	Gain	Kv4.3	KCND3	Giudicessi et al^Citation105
BrS11	INa	Loss		MOG1	Kattygnarath et al^Citation57
BrS12	IK-ATP	Gain	SUR2A	ABCC9	Barajas-Martínez et al^Citation61

Abbreviations: I_Na, sodium current; I_{Ca, L}, L-type calcium current; I_to, transient outward current; I_K-ATP, ATP-dependent potassium current.

Table 4 Catecholaminergic polymorphic ventricular tachycardia (CPVT)

Name	Current	Gain/loss of function	Protein	Gene	Reference
CPVT1	Irel	Leak	RyR2	RyR2	Laitinen et al,^Citation106 Priori et al^Citation107
CPVT2	Irel	Leak	Calsequestrin	CASQ2	Lahat et al,^Citation108 Postma et al^Citation109
CPVT3	IK1	Loss	Kir2.1	KCNJ2	Tester et al,^Citation22 Postma et al^Citation110
CPVT4	INCX, INaK, InsP3R	Loss	Ankyrin-B	ANKB	Mohler et al^Citation111

Abbreviations: RyR2, ryanodine receptor; I_rel, RyR2 Ca²⁺ release current; I_K1, inward-rectifier potassium current; I_NCX, Na⁺/Ca²⁺ exchanger current, I_NaK, Na⁺/K⁺ ATPase (pump) current; InsP₃R, inositol 1,4,5-trisphosphate (IP3) receptors.

Table 5 Short-QT syndrome (SQTS)

Name	Current	Gain/loss of function	Protein	Gene	Reference
SQT1	IKr	Gain	Kv11.1	KCNH2	Brugada et al^Citation112
SQT2	IKs	Gain	KvLQT1	KCNQ1	Bellocq et al^Citation113
SQT3	IK1	Gain	Kir2.1	KCNJ2	Priori et al^Citation114
SQT4	ICa,L	Loss	Cav1.2α1	CACNA1C	Antzelevitch et al^Citation58
SQT5	ICa,L	Loss	Cavβ2b	CACNB2b	Antzelevitch et al^Citation58
SQT6	ICa,L	Loss	Cavα2δ-1	CACNA2D1	Templin et al^Citation115

Abbreviations: I_Kr and I_Ks, rapid and slow delayed-rectifier potassium currents, respectively; I_K1, inward-rectifier potassium current; I_{Ca, L}, L-type calcium current.

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