Table 1

Hereditary channelopathies of excitable tissues

Gene	Locus	Channel protein	Disease	Inheritance	Change
Cardiac muscle
KCNQ1	11p15.5	Potassium channel α subunit, KCNQ1, KVLQT1	Long QT syndrome 1	Dominant	Loss
KCNQ1	11p15.5	Potassium channel α subunit, KCNQ1, KVLQT1	Jervell and Lange-Nielsen	Recessive	Loss
HERG	7q35-36	Potassium channel α subunit, HERG, eag related, Ikr	Long QT syndrome 2	Dominant	Loss
SCN5A	3p21	Sodium channel α subunit	Long QT syndrome 3	Dominant	Gain
SCN5A	3p21	Sodium channel α subunit	Brugada syndrome	Dominant	Loss
KCNE1	21q22	β subunit of KVLQT1, MinK	Long QT syndrome 5	Dominant	Loss
KCNE2		β subunit of HERG, MiRP1	Long QT syndrome inducible	Dominant	Loss
RYR2	1q42-43	Ryanodine receptor 1, calcium release channel type 2	Catecholaminergic ventricular fibrillation	Dominant	Gain
CASQ2	1p13-11	Calsequestrin type 2, fast twitch	Catecholaminergic ventricular fibrillation	Recessive	Gain
Skeletal muscle
SCN4A	17q23.1-25.3	Voltage gated sodium channel Nav1.4 α subunit	Hyperkalaemic periodic paralysis	Dominant	Gain
			Paramyotonia congenita	Dominant	Gain
			Potassium aggravated myotonia	Dominant	Gain
			Hypokalaemic periodic paralysis 2	Dominant	Loss
CACNA1S	1q31-32	Voltage gated L-type calcium channel α1 subunit, dihydropyridine (DHP) receptor	Hypokalaemic periodic paralysis type 1	Dominant	Unclear
CACNA1S	1q31-32		Malignant hyperthermia type 5	Dominant	Unclear
RYR1	19q13.1	Ryanodine receptor 1, calcium release channel	Malignant hyperthermia type 1	Dominant	Gain
RYR1	19q13.1	Ryanodine receptor 1, calcium release channel	Central core disease	Dominant	Gain
KCNJ2	17q23-24	Voltage insensitive potassium channel α subunit Kir2.1	Andersen’s syndrome, long QT syndrome 7	Dominant	Loss
CLCN1	7q32-qter	Voltage gated chloride channel ClC1	Thomsen myotonia	Dominant	Loss
		Voltage gated chloride channel ClC1	Becker myotonia	Recessive	Loss
		Altered splicing	Myotonic dystrophy type 1	Dominant	Loss
		Altered splicing	Myotonic dystrophy type 2	Dominant	Loss
ATP2A1	16p12	SERCA 1a, Ca-ATPase of sarcoplasmic reticulum, fast twitch 1	Brody’s syndrome	Dominant, recessive	Loss
Endplate
CHRNA1	2q24-32	nAChR α1 subunit	Congenital myasthenic syndrome (nAChR = nicotinic acetylcholine receptor)	Dominant and recessive	Gain and loss of function
CHRNB1	17p12-11	nAChR β1 subunit
CHRND	2q33-34	nAChR δ subunit
CHRNE	17	nAChR 1 subunit
RAPSN	11p11	Rapsyn, AChR associated protein	Congenital myasthenic syndrome	Recessive	Loss
Central nervous system
SCN1A	2q24	Nav1.1 sodium channel α subunit 1	Generalised epilepsy with febrile seizures plus (GEFS+2)	Dominant	?
SCN1B	19q13.1	β1 subunit
SCN2A	2q23	Nav1.2 sodium channel α subunit 2
SCN2A	2q23	Nav1.2 sodium channel α subunit 2	Benign familial neonatal/infantile convulsions	Dominant	?
KCNA1	12p13	Potassium ch α1 subunit, A-type, Kv1.1	Episodic ataxia type 1, partial epilepsy (?)	Dominant	Loss
KCNQ2	20q13.3	Voltage gated potassium channel α subunit Kv7.2	Benign familial neonatal convulsions	Dominant	Loss
KCNQ2	20q13.3	Voltage gated potassium channel α subunit Kv7.2	Neuromyotonia	Dominant	Loss
KCNQ3	8q??	Voltage gated potassium channel α subunit Kv7.3	Benign familial neonatal convulsions	Dominant	Loss
CACNA1A	19p13.1	Calcium channel P/Q-type α1 subunit	Episodic ataxia type 2	Dominant	Loss
			Familial hemiplegic migraine 1	Dominant	Loss
			Spinocerebellar ataxia type 6	Dominant	Loss
			Absence epilepsy	Dominant	Loss
CACNA1F	Xp11.23	Calcium channel retinal L-type α1 subunit	Congenital stationary night blindness (CSNB2)	Recessive	Loss
CLCN2	3q26	Voltage gated chloride channel ClC-2	Idiopathic generalised epilepsies	Dominant	Loss or gain
CACNB4	2q22-23	Calcium channel L-type β4 subunit	Generalised epilepsy	Dominant	Gain
CACNB4	2q22-23	Calcium channel L-type β4 subunit	Episodic ataxia 3	Dominant	Gain
CHRNA4	20q13.3	Nicotinic acetylcholine receptor α4 subunit	Nocturnal frontal lobe, ADNFLE	Dominant	Loss
GLRA1	5q31.2	Glycine receptor α1 subunit	Hyperekplexia = startle disease = stiff baby syndrome (STHE)	Dominant	Loss
GLRA1	5q31.2	Glycine receptor α1 subunit		Recessive	Loss