Table 3.
Pathogenic genes and pathogenic mechanisms of BrS.
| Gene | Protein | Chromosomal Location | Pathogenic Mechanism | Other Heart-Related Diseases |
|---|---|---|---|---|
| CACNA1C | Voltage-dependent L-type calcium channel subunit α-1C | 12p13.33 | ↓ICa | Timothy syndrome |
| CACNA2D1 [68] | Voltage-dependent calcium channel subunit α-2/delta-1 | 7q21.11 | ↓ICa | SQTS |
| CACNB2 [69] | Voltage-dependent L-type calcium channel subunit β-2 | 10p12 | ↓ICa | - |
| CALM2 [70] | Calmodulin-2 | 2p21 | ↓ICa | RWS, CPVT |
| TRPM4 [71] | Transient receptor potential cation channel subfamily M member 4 | 19q13.3 | ↓INa | PCCD |
| SCN5A [72] | Sodium channel protein type 5 subunit α | 3p22.2 | ↓INa | RWS, AF, AS, SSS, spontaneous ventricular fibrillation, PCCD |
| SCN10A [73] | Sodium channel protein type 10 subunit α | 3p22.2 | ↓INa | RWS |
| SCN1B [74] | Sodium channel subunit β-1 | 19q13.11 | ↓INa | PCCD, AF |
| * SCN2B [75] | Sodium channel subunit β-2 | 11q23.3 | ↓INa | AF |
| SCN3B [76] | Sodium channel regulatory subunit β-3 | 11q24.1 | ↓INa | AF |
| GPD1L [77] | Glycerol-3-phosphate dehydrogenase 1-like protein | 3p22.3 | ↓INa | - |
| * RANGRF [78] | Ran guanine nucleotide release factor | 17p13 | ↓INa | - |
| SLMAP [79] | Sarcolemmal membrane-associated protein | 3p14.3 | ↓INa | - |
| * PKP2 [80,81] | Plakophilin-2 | 12p11.21 | ↓INa | Isolated arrhythmic ventricular dysplasia, left ventricular insufficiency |
| KCND3 [82] | A-type voltage-gated potassium channel KCND3 | 1p13.2 | ↑It0 | - |
| KCNE3 [83] | Potassium voltage-gated channel subfamily E member 3 | 11q13.4 | ↑It0 | - |
| * KCNE5 [84] | Potassium voltage-gated channel subfamily E regulatory β subunit 5 | Xq23 | ↑IK,slow | - |
| KCNJ8 [85] | ATP-sensitive inward rectifier potassium channel 8 | 12p12.1 | ↑IK-ATP | - |
| HCN4 [86] | Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 | 15q24.1 | ↓If | SSS |
| ABCC9 [87] | ATP-binding cassette subfamily C member 9 | 12p12.1 | ↑IK-ATP | AF, idiopathic dilated cardiomyopathy |
| * AKAP9 [88] | A-kinase anchor protein 9 | 7q21.2 | - | RWS |
It0—transient outward potassium current; IK, slow—slow transient outgoing potassium current; IK-ATP—ATP sensitive potassium current; ICa—inward calcium current; INa—inward sodium current; If—inward pacemaker current formed by selective cation channels conducting Na+ and Ca2+; SQTS—short QT syndrome; RWS—Romano–Ward syndrome; CPVT—catecholaminergic polymorphic ventricular tachycardia; PCCD—progressive cardiac conduction defect; AF—atrial fibrillation; AS—atrial standstill; SSS—sick sinus syndrome. * Candidate gene. The gene comes from HGNC. The names of chromosome loci and loci come from OMIM. The protein comes from UniProt. Genetically related diseases come from Orphanet.