Table 7. Evaluation of stability changes of 15 functionally characterized and 9 functionally uncharacterized PITX2 homeodomain missense variants using eight different protein stability prediction programs.
| No. | Variations | DUET | SDM | mCSM | I-Mutant3.0 SEQ | I-Mutant3.0 Structure | MUpro | iPTREE-STAB | CUPSAT | iStable |
|---|---|---|---|---|---|---|---|---|---|---|
| Characterised variants | ||||||||||
| 1 | R43W | -1.773 | 0.35 | -0.97 | 0.00 | -0.13 | -0.162 | 0.0337 | -75.87 | 0.0077 |
| 2 | H45Q | 0.158 | -0.15 | 0.027 | 0.07 | 0.17 | -0.112 | -2.9050 | 19.1 | 0.3529 |
| 3 | Q49L | 0.471 | 0.29 | 0.186 | 0.38 | 0.68 | 1 | 0.9422 | -5.82 | 0.6946 |
| 4 | L54Q* | -2.892 | -2.3 | -2.73 | -1.65 | -1.50 | -1 | -1.8488 | 3.85 | -0.9075 |
| 5 | P64S | -2.069 | -1.27 | -1.97 | -1.59 | -1.57 | -1 | -1.0233 | -45.88 | -0.9568 |
| 6 | M66T | 0.444 | -0.67 | 0.181 | -1.20 | -0.32 | -1 | 1.0943 | 10.62 | -0.1104 |
| 7 | T68P | -0.359 | -0.34 | -0.361 | -0.90 | -0.68 | 0.155 | -1.0594 | 0.38 | 0.2945 |
| 8 | R69H | -2.369 | -0.15 | -2.147 | -1.56 | -1.29 | -0.633 | -1.3667 | 8.49 | -0.7126 |
| 9 | T76S | -1.35 | -0.79 | -1.211 | -0.69 | -0.26 | -0.014 | 0.9377 | -16.05 | -0.0892 |
| 10 | V83L* | -0.305 | 0.09 | -0.44 | -0.91 | -0.72 | 0.224 | -1.3883 | -2.72 | -0.3060 |
| 11 | R84W | -1.056 | -0.06 | -1.125 | -0.52 | 0.41 | -0.966 | -2.9167 | -23.81 | -0.1240 |
| 12 | K88E | -1.759 | 0.87 | -1.777 | -0.32 | -0.24 | -0.024 | -0.9691 | 8.8 | -0.1765 |
| 13 | R90C | -2.014 | -0.49 | -2.019 | -0.86 | -0.89 | -0.567 | -0.6385 | -19.6 | -0.4268 |
| 14 | R91P* | -2.225 | -2.25 | -1.777 | -0.82 | -0.93 | -1 | -2.7464 | -75.47 | -0.6208 |
| 15 | R91Q | -1.308 | -0.08 | -1.3 | -0.95 | -1.04 | -1 | 0.3362 | 37.96 | -0.4777 |
| Uncharacterised variants | ||||||||||
| 1 | F58L* | -0.868 | 0.64 | -0.882 | -0.69 | -0.71 | 0.446 | -1.3492 | 8.37 | 0.4267 |
| 2 | R62H | -1.839 | 0.2 | -1.757 | -1.24 | -1.17 | -0.634 | -2.1794 | -1.72 | -0.6073 |
| 3 | P64L | -0.55 | 0.32 | -0.845 | -0.07 | -0.64 | -0.260 | -4.1000 | -5.02 | -0.1755 |
| 4 | P64R | -0.979 | -2.07 | -0.944 | -0.83 | -1.09 | -0.892 | -0.8385 | -13.21 | -0.5091 |
| 5 | R69C | -2.183 | 0.23 | -2.107 | -1.12 | -1.07 | -0.183 | 0.2429 | 0.51 | -0.5278 |
| 6 | V83F* | -1.437 | -1.32 | -1.265 | -1.16 | -1.12 | -0.496 | -1.3883 | -10.94 | -0.6159 |
| 7 | W86S* | -2.327 | -2.67 | -2.514 | -1.64 | -1.55 | -1 | -0.6167 | -31.26 | -1.0663 |
| 8 | W86C* | -0.931 | -1.57 | -1.018 | -1.52 | -1.40 | -0.971 | 0.6923 | -12.15 | -0.8733 |
| 9 | R90P | -1.623 | -2.25 | -1.319 | -0.71 | -0.74 | -0.346 | -2.8825 | -23.89 | -0.3739 |
*Predicted by molecular modeling to destabilize the structure and function of PITX2 protein.