Functional analysis of SCN8A mutations identified in heterozygous state in patients with intellectual disability (ID) with or without epileptic encephalopathy (EE)
| Protein change | ID | EE | Cell assay | Effect on function | Ref. | Channel domain |
|---|---|---|---|---|---|---|
| N1768D | + | + | Neuronal | GOF, increased persistent current | 25 | In D4S6 |
| T1716I | + | + | Neuronal | GOF, hyperpolarizing shift in activation voltage | 28 | In D2S1 |
| N984K | + | + | HEK | GOF, hyperpolarizing shift in activation voltage | This article | Near D2S6 |
| G1451S | + | + | HEK | LOF at 37°C | This article | in D3S6 |
| R223G | + | + | HEK | Partial LOF; thermolabile. Protein is unstable at 37°C, active at 30°C | 32 | In D1S4 |
| P1719Rfs*6 | + | − | None | LOF, protein truncation | 24 | In D4S5-S6 |
| D58N | + | − | HEK | Wildtype activity; may be non-pathogenic in view of additional de novo mutation | This article | In N-term |
Missense mutations were introduced into the mouse NaV1.6 cDNA and cells were transfected for electrophysiological assays. Only the deduced protein changes (one-letter code) are provided.
GOF, gain of function; LOF, loss of function.