Table 4.
TRPV4 mutations analyzed and summary of in vitro results.
| TRPV4 genotype | Clinical syndrome | Protein domain | In vitro results | |||
|---|---|---|---|---|---|---|
| Baseline calcium | Stimulated calcium | Cell death (%) | GSK219 IC50 (nM) | |||
| WT | — | — | 0.73 | 1.76 | 7.2 | 8.0 |
| R269C | Neuropathy with vocal cord weakness | ARD3 | 0.88 | 2.56 | 11.3 | 10.0 |
| D333G | Skeletal dysplasia | ARD5 | 1.12 | 2.36 | 10.7 | 20.7 |
| S542Y | Neuropathy with vocal cord weakness, short stature | Ligand binding | 1.19 | 2.74 | 12.2 | 55.3 |
| R616Q | Skeletal dysplasia | TM5 | 0.87 | 2.09 | 8.2 | 11.9 |
| R616G | Neuropathy with vocal cord weakness | TM5 | 1.83 | 1.99 | 26.3 | 215.6 |
| L619P | Severe neuropathy with vocal cord weakness, skeletal dysplasia, giant cell jaw lesions | TM5 | 2.17 | 2.37 | 28.5 | 198.4 |
| W785C | Mild neuropathy without vocal cord weakness, skeletal dysplasia, scaly skin | C terminal | 1.18 | 2.09 | 15.0 | 31.5 |
Baseline and stimulated calcium response values indicate Fura ratios (340/380). Abbreviations: ARD, ankyrin repeat domain; TM, transmembrane domain; IC50, half maximal inhibitory concentration.