Table 2. Summary of potassium channel rare variants associated with AF.
| Gene | Gene product | Nucleotide substitution | Amino-acid substitution | Documented family co-segregation | Electrophysiological consequence | Reference | Found in ESP EA minor/minor/ minor/major | Found in ESP AA minor/minor/ minor/major | Found in ESP all minor/minor/ minor/major |
|---|---|---|---|---|---|---|---|---|---|
| KCNQ1 | α-Subunit of IKs | c.40C>T | p.(Arg14Cys) | Yes | Gain-of-function | 53 | 0/0 | 0/0 | 0/0 |
| c.160_168insATCGCGCCC | p.(54_56insIleAlaPro) | Yes | Gain-of-function | 52 | 0/0 | 0/0 | 0/0 | ||
| c.418A>G | p.(Ser140 Gly) | Yes | Gain-of-function | 48 | 0/0 | 0/0 | 0/0 | ||
| c.421G>A | p.(Val141Met) | No | Gain-of-function | 49 | 0/0 | 0/0 | 0/0 | ||
| c.625C>T | p.(Ser209Pro) | Yes | Gain-of-function | 50 | 0/0 | 0/0 | 0/0 | ||
| c.692G>A | p.(Arg231His) | Yes | Gain-of-function | 54 | 0/0 | 0/0 | 0/0 | ||
| c.693C>T | p.(Arg231Cys) | Yes | Gain-of-function | 51 | 0/0 | 0/0 | 0/0 | ||
| KCNE1 | β-Subunit of IKs | c.74C>T | p.(Gly25Val) | No | Gain-of-function | 55 | 0/0 | 0/0 | 0/0 |
| c.179G>A | p.(Gly60Asp) | Yes | Gain-of-function | 55 | 0/0 | 0/0 | 0/0 | ||
| KCNE2 | β-Subunit of IKs | c.79C>T | p.(Arg27Cys) | Yes | Gain-of-function | 56 | 0/0 | 0/0 | 0/0 |
| KCNE3 | β-Subunit of IKs | c.49G>A | p.(Val17Met) | No | Gain-of-function | 12 | 0/0 | 0/0 | 0/0 |
| KCNE4 | β-Subunit of IKs | c.422A>C | p.(Glu141Ala) | ? | Possible change | 57 | 0/5 | 0/0 | 0/5 |
| KCNE5 | β-Subunit of IKs | c.193C>T | p.(Leu65Phe) | No | Gain-of-function | 13 | 0/0 | 0/0 | 0/0 |
| KCND3 | Kv4.3 | c.5C>A | p.(Ala2Glu) | ? | No change | 57 | 0/0 | 0/0 | 0/0 |
| c.641A>G | p.(Lys214Arg) | ? | No change | 57 | 0/4 | 0/0 | 0/4 | ||
| c.1633G>C | p.(Ala545Pro) | ? | Gain-of-function | 118 | 0/0 | 0/0 | 0/0 | ||
| KCNH2 | α-Subunit of IKr | c.526C>T | p.(Arg176Trp) | No | Loss-of-function | 57, 121 | 0/0 | 0/0 | 0/0 |
| c.1330G>A | p.(Glu444Lys) | Yes | Loss-of-function | 57 | 0/0 | 0/0 | 0/0 | ||
| c.1764C>G | p.(Asn588Lys) | Yes | Gain-of-function | 58, 59 | 0/0 | 0/0 | 0/0 | ||
| KCNJ2 | Kir2.1 | c.277G>A | p.(Val93Ile) | Yes | Gain-of-function | 60 | 0/2 | 0/1 | 0/3 |
| KCNJ8 | Kir6.1 | c.1265C>T | p.(Ser422Leu) | ? | Gain-of-function | 61, 62 | 0/19 | 0/1 | 0/20 |
| KCNA5 | Kv1.5 | c.143A>G | p.(Glu48Gly) | No | Gain-of-function | 66 | 0/0 | 0/0 | 0/0 |
| c.211_243 | p.(71_81del) | Yes | Loss-of-function | 65 | NA | NA | NA | ||
| c.464A>G | p.(Tyr155Cys) | No | Loss-of-function | 66 | 0/0 | 0/0 | 0/0 | ||
| c.913G>A | p.(Ala305Thr) | Yes | Gain-of-function | 66 | 0/0 | 0/0 | 0/0 | ||
| c.964G>C | p.(Asp322His) | No | Gain-of-function | 66 | 0/0 | 0/0 | 0/0 | ||
| c.1123G>T | p.(Glu375Ter) | Yes | Loss-of-function | 63 | 0/0 | 0/0 | 0/0 | ||
| c.1407C>A | p.(Asp469Glu) | No | Loss-of-function | 66 | 0/0 | 0/0 | 0/0 | ||
| c.1462C>T | p.(Pro488Ser) | No | Loss-of-function | 66 | 0/0 | 0/0 | 0/0 | ||
| c.1580C>T | p.(Thr527Met) | Yes | Loss-of-function | 46, 64 | 0/0 | 0/0 | 0/0 | ||
| c.1703G>T | p.(Gly568Val) | Yes | Gain-of-function | 57 | 0/3 | 0/0 | 0/3 | ||
| c.1727C>T | p.(Ala576Val) | Yes | Loss-of-function | 46 | 0/0 | 0/0 | 0/0 | ||
| c.1828G>A | p.(Glu610Lys) | Yes | Loss-of-function | 46 | 0/0 | 0/0 | 0/0 | ||
| ABCC9 | KATP channel | c.4640C>T | p.(Thr1547Ile) | ? | Loss-of-function | 67 | 0/0 | 0/0 | 0/0 |
Abbreviations: AA, African American; EA, European American; ESP, NHLBI GO Exome Sequencing Project; NA, data regarding major InDel is not available in EVS.