Table 1.

Genes encoding cardiac ion channels and signaling proteins that have been associated with early-onset familial AF.

Gene	Mode of inheritance	Effect on function	Physiologic effect	Associated phenotypes
ABCC9	unknown	loss-of-function	↓ atrial APD	adrenergic AF
KCNQ1	AD	gain-of-function	↓ atrial APD	prolonged QT
KCNE1 KCNE5	AD AD	gain-of-function gain-of-function	↓ atrial APD ↓ atrial APD	frequent PACs
KCNJ2	AD	gain-of-function	↓ atrial APD
GJA5	somatic mutations in isolated early-onset AF cases	↓electrical cell-to-cell coupling	regions of heterogeneous conduction
KCNA5	AD	loss-of-function	↑ atrial APD, EADs and TA
SCN5A SCN1B/2B	AD AD	gain-of-function and loss-of-function	↑↓ atrial APD EADs, TA	HCM, DCM
SCN10A	AD	enhanced late INa	↑APD, EADs, TA	slow ventricular rates
CACNA1C CACNB2	AD AD	loss-of-function loss-of-function	↑APD, EADs, TA ↑APD, EADs, TA
NKX2.6	AD	Loss-of-function	Reduced transcriptional activity of ANP promoter	None
TBX5	unknown	Increased expression of ANP and CX40		Early-onset AF
NPPA	AD	loss-of-function	↓ atrial APD	atrial myopathy
NUP155	AR	nuclear protein transport (hsp70)		sudden cardiac death

Modified from³⁰

AD, autosomal dominant; APD, action potential duration; AR, autosomal recessive; PAC, premature atrial contractions; EAD, early after-depolarization; TA, triggered activity.