Table 6.
Functional consequences of HSPB1 mutations. NTD: N-terminal domains, CTD: C-terminal domains.
| Domain | Mutation 1 | Inheritance 2 | Oligomer Size | Oligomer Stability | Oligomer Sensitivity to Phosphorylation | Dimerization | Chaperone Function | Client Binding | Thermal Stability | Aggregation | Cytotoxicity | Cell Stress Tolerance | Effects on Neurofilaments | Effects on Microtubules | Susceptibility to Proteasomal Degradation Mutant HSPB1 | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NTD | P7S | D | = | – | + | [337] | ||||||||||
| G34R | D | + | + | – | – | [336,350] | ||||||||||
| P39L | D | + | + | – | ± | + | [334,350,360] | |||||||||
| E41K | D | + | + | – | – | [336,350] | ||||||||||
| G53D | R | = | – | + | [337] | |||||||||||
| L58Afs*105 | D | = | + | [337,340] | ||||||||||||
| A61Rfs*100 | D | = | + | [337] | ||||||||||||
| G84R | D | + | – | + | – | (+) | [331,334,348] | |||||||||
| S86L | R | [342] | ||||||||||||||
| ACD | L99M | R | + | – | + | – | (+) | [331,334,348] | ||||||||
| R127W | D | + | – | + | – | + | + | – | + | + | [170,333,347,358] | |||||
| R127L | D | – | [365] | |||||||||||||
| Q128R | D | = | – | + | [337] | |||||||||||
| D129E | D | [345] | ||||||||||||||
| S135F | D | + | – | + | – | + | + | = | + | + | + | + | [170,333,347,356,358,360] | |||
| R136W | D | + | – | – | + | + | = | = | + | [170,333,347,358] | ||||||
| R140G | SD | ++/– | – | ≈ | – | – | + | + | (+) | [210,331,334,339,346,360] | ||||||
| K141Q | D | (+) | – | – | – | (+) | [331,346,368] | |||||||||
| T151I | D | = | = | = | = | = | [170,333,358] | |||||||||
| T164A | D | – | = | [349,369] | ||||||||||||
| M169Cfs*2 | D | = | – | – | [365] | |||||||||||
| CTD | T180I | D | ≈ | [335,349] | ||||||||||||
| P182S | D | + | + | = | – | + | (+) | [331,349,370] | ||||||||
| P182L | D | + | = | = | + | – | + | = | [170,333,351,358] | |||||||
| S187L | D | = | + | – | [337] | |||||||||||
| R188W | D | – | – | = | [336,349] | |||||||||||
| A204Gfs*6 | D | + | – | [343] |
The table shows a selected subset of HSPB1 mutations for which functional information is available. 1 Reference sequence NP_001531.1 2 D, dominant; R, recessive; SD, semidominant.