Table 3.
Non–Ion Channel Mutations Linked to AF
| Gene | Locus | Product | Function/Mechanism | Type | References |
|---|---|---|---|---|---|
| NUP155 | 5p13.2 | Nucleoporin 155 | Nuclear pore complex/reduction in nuclear membrane permeability | LOF | 57 and 58 |
| LMNA | 1q22 | Lamin A/C | Nuclear envelope structure | … | 60 and 61 |
| GJA1 | 6q22.31 | Connexin43 | Gap‐junction protein/impaired intracellular transport and intercellular electrical coupling | LOF | 62 |
| GJA5 | 1q21.2 | Connexin40 | Gap‐junction protein/impaired intracellular transport and intercellular electrical coupling | LOF | 63–67 |
| NPPA | 1p36.22 | Natriuretic peptide precursor | Blood pressure regulation/elevated levels of mutant ANP | GOF | 11 and 68–70 |
| GATA4 | 8p23.1 | Cardiac transcription factor | Cardiogenesis | LOF | 71 and 72 |
| GATA5 | 20q13.33 | Cardiac transcription factor | Cardiogenesis | LOF | 73 and 74 |
| GATA6 | 18q11.2 | Cardiac transcription factor | Cardiogenesis | LOF | 75–77 |
| NKX2‐5 | 5q35.1 | Homeobox protein Nkx‐2.5 | Cardiogenesis | LOF | 80–82 |
| NKX2‐6 | 8p21.2 | Homeobox protein Nkx‐2.6 | Cardiogenesis | … | 84 |
| PITX2 | 4q25 | Pituitary homeobox 2 | Cardiogenesis | LOF | 86 |
| GREM2 | 1q43 | Gremlin‐2 | Bone morphogenetic protein antagonist | GOF | 87 |
| JPH2 | 20q13.12 | Juctophilin‐2 | Calcium homeostasis | LOF | 88 |
| RYR2 | 1q43 | Ryanodine receptor 2 | Calcium homeostasis | GOF | 89 |
| AGT | 1q42.2 | Angiotensinogen | Renin‐angiotensin system | … | 90 |
| ACE | 17q23.3 | Angiotensinogen converting enzyme | Renin‐angiotensin system | … | 90 |
| GNB3 | 12p13.31 | β3‐Subunit of heterotrimeric G protein | Signal integration | … | 92 |
| IL6 | 7p15.3 | Interleukin‐6 | Cytokine | … | 93 |
| IL10 | 1q32.1 | Interleukin‐10 | Cytokine | … | 94 |
| MMP2 | 16q12.2 | Matrix metalloproteinase‐2 | Zinc‐dependent enzyme | … | 94 |
| SLN | 11q22.3 | Sarcolipin | Sarcoplasmic reticulum calcium‐ATPase | … | 95 |
| eNOS | 7q36.1 | Endothelial NO synthase | Regulates L‐type calcium channel | … | 96 |
| CETP | 16q13 | Cholesteryl ester transfer protein | Transfer between lipoproteins | … | 97 |
| SYNE2 | 14q23.2 | Nesprin‐2 | Cytoskeleton LINC complex | … | 38 |
| ZFHX3 | 16q22.2 to 2q22.3 | Zinc finger homeobox 3 | Transcription factor | … | 38 |
AF indicates atrial fibrillation; ANP, atrial natriuretic peptide; GOF, gain of function; LINC, linker of the nucleoskeleton and cytoskeleton complex; LOF, loss of function.