Table 1. Comparison of in vitro and in silico predicted activities of aminoacidic variants in CYP21A2 presumed to be involved in protein stability published since 2014.
| Mutation |
In vitro activity ± SD |
In silico activity |
Patient’s second mutation (REA%) | Patient’s phenotype | Reference | ||
|---|---|---|---|---|---|---|---|
| 17- OHP | P | Bovine model | Human crystal structure | ||||
| p.P45L | 105 ± 10 | ND | 0.74 | 1.46 | ND | SV | 21 |
| p.K102R | 119.7 ± 25 | ND | 63.16 | ≥100 | ND | NA | 21 |
| p.L122P | 1.4 ± 2.1 | −1.9 ± 5.2 | 0.11 | 0.25 | Deletion (0) | SW | 22 |
| p.R149C | 35.8 ± 14.6 | 47.3 ± 12.9 | ≥100 | ≥100 | p.V281L (60) | NC | 23 |
| p.M150R | 17.7 ± 1.9 | 4.6 ± 1.9 | 0.9 | 4.4 | N | PB | 22 |
| p.A159T | 126.6 ± 29.9 | ND | ≥100 | ≥100 | N | AD | 21 |
| p.V211M | 99.5 ± 32.4 | ND | ≥100 | ≥100 | ND | SV/NC | 21 |
| p.A265S | 90 ± 9 | 104 ± 15 | ≥100 | ≥100 | N | NA | 24 |
| p.M283V | 16.2 ± 9.3 | 19 ± 7 | 41.8 | 38.14 | Deletion (0) | NC | 23 |
| p.M473I | 85 ± 7 | 66 ± 12 | ≥100 | 64.12 | p.V281L (60) | NC | 24 |
In silico enzymatic activities were calculated from the fitting of the bovine based model and from the human crystal (Fig. 1) using the estimated ∆∆Gs of each of the mutants (Table S1). In vitro and in silico enzymatic activities are expressed in percentage relative to the wild type protein considered as 100%. In vitro enzymatic activities, patients’ second mutation and phenotypes are those reported in the bibliography. 17-OHP: 17-hydroxyprogesterone. P: Progesterone. REA: Residual enzymatic activity. ND: Not determined. N: Normal; NC. Nonclassical; SV: Simple virilizing; SW: Salt wasting; NA: Not Affected; PB: Premature Pubarche; AD: Addison Disease.