Table 2.
In-Vitro Functional Characteristics of MCT8 Mutations
| Mutation | Functional analysis |
Subcellular localization |
Main cellular pathogenic mechanism | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Protein expression |
Uptake |
Metabolism |
PM |
ER |
||||||||
| COS1 | JEG3 | Flp-in 293 | COS1 | JEG3 | Flp-in 293 | COS1 | JEG3 | Flp-in 293 | JEG3 | Flp-in 293 | ||
| G221R | n | n | n.d. | − | − | n.d. | − | − | n.d. | + | n.d. | Loss of transport activity |
| insV236 | low | low | low | − | − | − | + | − | − | − | + | Protein degradation and trafficking defect plus partial loss of transport activity |
| G282C | low | low | low | + | − | − | + | − | − | − | + | Decreased protein synthesis and/or increased protein degradation |
| P321L | n | n | n | − | − | + | − | − | + | + | + | Loss of transport activity |
| D453V | n | n | n.d. | − | − | n.d. | + | − | n.d. | + | n.d. | Loss of transport activity |
| P537L | n | n | n | + | − | + | + | − | + | + | + | Loss of transport activity |
| G558D | low | low | low | + | − | + | + | − | − | − | + | Decreased protein synthesis and/or increased protein degradation |
Functional analysis: n, normal, similar to WT; low, lower expression than WT; −, no significant difference compared with empty vector for T3 uptake; +, significant T3 uptake compared with empty vector; n.d., not done; −, no significant difference compared to D3 alone for T3 metabolism; +, significant T3 metabolism compared to D3 alone.
Subcellular localization: −, minimal if any colocalization; +, colocalization.