Table 1 Categories of FBP1 missense mutations.
Mutation | Location | Enzymatic activity | Protein expression | Intracellular | Aggregation | Chaperone binding ability | Type of amino acid | Hydropathy index | Structure | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Amino acid change | Compared to wild-type | Compared to wild-type | Localization | (%) | HSP70 | HSP90 | Wild-type | Mutant | Wild-type | Mutant | |||
Type 1: Loss of enzyme activity due to mutations in functional domain with unchanged protein expression and diffuse cytoplasmic localization | |||||||||||||
D119N | Metal binding site | Decrease | No change | 1.4 | Diffuse (cytoplasm) | 9.4 | 0.1 | 0.3 | Hydrophilic-acidic | Hydrophilic-neutral | −3.5 | −3.5 | β-strand |
P120L | Linker lesion at metal and substrate binding site | Decrease | No change | 1.3 | Diffuse (cytoplasm) | 8.5 | 1.1 | 0.5 | Hydrophobic-aliphatic | Hydrophobic-aliphatic | −1.6 | 3.8 | β-strand |
N213K | Substrate binding site | Decrease | No change | 1.1 | Diffuse (cytoplasm) | 13.3 | 1.5 | 0.5 | Hydrophilic-neutral | Hydrophilic-basic | −3.5 | −3.9 | ND |
E281K | Metal binding site | Decrease | No change | 0.9 | Diffuse (cytoplasm) | 33.6 | 2.4 | 0.5 | Hydrophilic-acidic | Hydrophilic-basic | −3.5 | −3.9 | turn |
Type 2: Loss of enzyme activity with decreased protein expression and ER aggregation in association with hydrophobicity change | |||||||||||||
R158W | Decrease | Decrease | 0.5 | Aggregated (in ER) | 69.6 | 7.7 | 7.8 | Hydrophilic-basic | Hydrophobic-aromatic | −4.5 | −0.9 | α-helix | |
G164D | Decrease | Decrease | 0.4 | Aggregated (in ER) | 71.4 | 13.7 | 15.8 | Hydrophobic-aliphatic | Hydrophilic-acidic | −0.4 | −3.5 | β-strand | |
G164S | Decrease | Decrease | 0.6 | Aggregated (in ER) | 42.7 | 6.4 | 12.2 | Hydrophobic-aliphatic | Hydrophilic-neutral | −0.4 | −0.8 | β-strand | |
A177D | Decrease | Decrease | 0.2 | Aggregated (in ER) | 73.9 | 24.0 | 37.5 | Hydrophobic-aliphatic | Hydrophilic-acidic | 1.8 | −3.5 | β-strand | |
F194S | Decrease | Decrease | 0.4 | Aggregated (in ER) | 62.6 | 15.4 | 19.8 | Hydrophobic-aromatic | Hydrophilic-neutral | 2.8 | −0.8 | β-strand | |
G260R | Decrease | Decrease | 0.4 | Aggregated (in ER) | 73.5 | 18.9 | 28.2 | Hydrophobic-aliphatic | Hydrophilic-basic | −0.4 | −4.5 | ND | |
P284R | Decrease | Decrease | 0.3 | Aggregated (in ER) | 57.7 | 41.2 | 47.2 | Hydrophobic-aliphatic | Hydrophilic-basic | −1.6 | −4.5 | α-helix | |
G294E | Decrease | Decrease | 0.4 | Aggregated (in ER) | 64.1 | 64.9 | 89.9 | Hydrophobic-aliphatic | Hydrophilic-acidic | −0.4 | −3.5 | ND | |
G294V | Decrease | Decrease | 0.6 | Aggregated (in ER) | 65.9 | 6.1 | 3.5 | Hydrophobic-aliphatic | Hydrophobic-aliphatic | −0.4 | 4.2 | ND | |
Type 3: Likely non-pathogenic mutations in regard to biochemical phenotype | |||||||||||||
G207R | No change | No change | 1.0 | Diffuse (cytoplasm) | 12.7 | 3.1 | 3.9 | Hydrophobic- aliphatic | Hydrophilic-basic | −0.4 | −4.5 | ND | |
V325A | No change | No change | 1.0 | Diffuse (cytoplasm) | 25.4 | 2.3 | 1.3 | Hydrophobic-aliphatic | Hydrophobic-aliphatic | 4.2 | 1.8 | α-helix | |
