Table 2.
Mutations identified in KCNJ16/Kir5.1.
| Mutation | CADD Score | Associated phenotypes | Function with Kir4.1 | Function with Kir4.2 | Reference | |||
|---|---|---|---|---|---|---|---|---|
| H | A | D | SIDS | |||||
| K48* | 36 | Y | N | ND | ND | ND | Webb et al., 2021 | |
| T64I | 23.8 | Y | N | Y | Reduced by 70% | Reduced by >90% | Schlingmann et al., 2021 | |
| I132R | 24.7 | Y | (Y) | Y | Reduced by 74% | Reduced by >90% | Schlingmann et al., 2021 | |
| G135A | 24.4 | Y | (Y) | Y | ND | ND | Schlingmann et al., 2021 | |
| R137C | 25.2 | Y | Y | Y | Reduced by 83% | Reduced by >90% | Schlingmann et al., 2021 | |
| R137S | 24.2 | ND | ND | ND | Y | Reduced by 80% | ND | Neubauer et al., 2022 |
| R176* | 34 | Y | (Y) | Y | Reduced by 54% | Reduced by >90% | Schlingmann et al., 2021 | |
| A188S | 23.5 | ND | ND | ND | Y | Increased by 10% | ND | Neubauer et al., 2022 |
| P250L | 23.4 | Y | (Y) | Y | Reduced by 39% | Reduced by >90% | Schlingmann et al., 2021 | |
| >25% Residual function | ||||||||
| <25% Residual function | ||||||||
| Atypical features | ||||||||
| Gain of function | ||||||||
| Function unknown | ||||||||
Table 2 summarizes the consequences of KCNJ16 mutations. CADD score according to https://cadd.gs.washington.edu/snv (Rentzsch et al., 2019). Associated phenotypes refer to hypokalemia (H), acidosis (A), sensorineural deafness (D), and a possible association with sudden infant death syndrome (SIDS). Yes (Y); probably Yes (Y); No (N); Not examined (ND). Color code is shown for functional effects when coexpressed with Kir4.1. * indicates a “stop codon”. Note that functional consequences were generally more severe when Kir5.1 mutants were coexpressed with Kir4.2 (Schlingmann et al., 2021).