Table 4.
Pathogenic genes and pathogenic mechanisms of familial AF.
| Gene | Protein | Chromosomal Location | Pathogenic Mechanism | Other Heart-Related Diseases |
|---|---|---|---|---|
| KCNA5 [99] | Potassium voltage-gated channel subfamily A member 5 | 12p13.32 | ↑↓IKur | - |
| KCNJ2 [107] | Inward rectifier potassium channel 2 | 17q24.3 | ↑IK1 | ATS, SQTS |
| KCNQ1 [107,108] | Potassium voltage-gated channel subfamily KQT member 1 | 11p15.5-p15.4 | ↑IKs | RWS, JLNS, SQTS |
| * KCNE1 [108] | Potassium voltage-gated channel subfamily E member 1 | 21q22.12 | ↑IKs | JLNS, RWS |
| KCNE2 [107] | Potassium voltage-gated channel subfamily E member 2 | 21q22.11 | ↑IKr | RWS |
| * SCN1B | Sodium channel subunit β-1 | 19q13.11 | ↑INa | BrS, PCCD |
| SCN2B | Sodium channel subunit β-2 | 11q23.3 | ↑INa | BrS |
| SCN3B | Sodium channel regulatory subunit β-3 | 11q24.1 | ↑INa | BrS |
| SCN4B | Sodium channel subunit β-4 | 11q23.3 | ↑INa | RWS |
| SCN5A [109] | Sodium channel protein type 5 subunit α | 3p22.2 | ↑INa | RWS, BrS, SSS, AS, spontaneous ventricular fibrillation, PCCD |
| * ABCC9 [110] | ATP-binding cassette subfamily C member 9 | 12p12.1 | ↑IK-ATP | BrS, idiopathic dilated cardiomyopathy |
| GATA4 [111] | Transcription factor GATA-4 | 8p23.1 | ↓Transcriptional activity | Tetralogy of fallot, etc. |
| GATA5 [112] | Transcription factor GATA-5 | 20q13.33 | ↓Transcriptional activity | Tetralogy of fallot, etc. |
| GATA6 [113] | Transcription factor GATA-6 | 18q11.2 | ↑Transcriptional activity | Tetralogy of fallot, etc. |
| NKX2-5 [101] | Homeobox protein Nkx-2.5 | 5q34 | ↑HCN4 | PCCD, hypoplastic left heart syndrome, etc. |
| NKX2-6 [114] | Homeobox protein Nkx-2.6 | 8p21.2 | Similar to NKX2-5 | Tetralogy of fallot, persistent truncus arteriosus |
| PITX2 [101] | Pituitary homeobox 2 | 4q25 | ↓NKX2-5 | Axenfeld abnormal, Rieger abnormal, etc. |
| MYL4 [115] | Myosin light chain 4 | 17q21.32 | Ligandin | - |
| TTN [116,117] | Titin | 2q31.2 | - | Familial isolated dilated cardiomyopathy, early-onset myopathy with fatal cardiomyopathy, isolated arrhythmia ventricular dysplasia |
| GJA5 [103] | Gap junction α-5 protein | 1q21.2 | Ligandin | Tetralogy of fallot |
| NPPA [105] | Natriuretic peptides A | 1p36.22 | Channel remodeling | AS |
| NUP155 [106] | Nuclear pore complex protein Nup155 | 5p13.2 | ↓Nuclear membrane permeability | - |
IKs—slow delay rectifier potassium current; IKr—fast delay rectifier potassium current; IK1—inward rectifying potassium current; IKur—atrial specific potassium current; IK-ATP—ATP sensitive inward rectifying potassium current; INa—voltage dependent sodium current; ATS—Andersen Tawil syndrome; SQTS—short QT syndrome; RWS—Romano–Ward syndrome; JLNS—Jervell–Lange–Nielsen syndrome; BrS—Brugada syndrome; PCCD—progressive cardiac conduction defect; SSS—sick sinus syndrome; AS—atrial standstill. * 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.