Table 1.
Summary of biochemical analysis of TMD1 variants.
| Variant | Localization | Relative Solubilization | Basal ATPase Activity | N-Ret-PE-Induced ATPase Activity |
N-ret-PE Binding no ATP |
N-Ret-PE Binding with ATP | Class * | Predicted Severity |
|---|---|---|---|---|---|---|---|---|
| WT | Vesicles/ER | 100 | 100 | 222 ± 22 | 100 | 15 ± 7 | -- | Normal |
| R653C | Vesicles/ER | 102 ± 9 | 113 ± 21 | 134 ± 17 | 17 ± 12 | 15 ± 10 | 1 | Severe |
| R653H | Vesicles/ER | 115 ± 14 | 130 ± 15 | 239 ± 39 | 31 ± 12 | 9 ± 3 | 2 | Moderate/ Mild * |
| L661R | ER | 20 ± 11 | 13 ± 4 | 16 ± 3 | 36 ± 6 | 18 ± 2 | 1 | Severe |
| L686S | ER | 27 ± 8 | 18 ± 9 | 30 ± 16 | 16 ± 8 | 11 ± 7 | 1 | Severe |
| G690V | ER | 33 ± 12 | 41 ± 12 | 59 ± 14 | 21 ± 9 | 11 ± 7 | 1 | Severe |
| T716M | Vesicles/ER | 98 ± 16 | 94 ± 4 | 228 ± 13 | 59 ± 7 | 9 ± 8 | 3 | Mild |
| C764Y | Vesicles/ER | 100 ± 12 | 133 ± 5 | 270 ± 39 | 68 ± 6 | 16 ± 7 | 3 | Mild |
| S765N | ER | 30 ± 9 | 21 ± 9 | 45 ± 7 | 19 ± 5 | 16 ± 5 | 1 | Severe |
| S765R | ER | 29 ± 11 | 18 ± 6 | 29 ± 4 | 13 ± 4 | 18 ± 3 | 1 | Severe |
| V767D | ER | 24 ± 11 | 40 ± 14 | 63 ± 17 | 21 ± 1 | 20 ± 2 | 1 | Severe |
| L797P | ER | 25 ± 5 | 31 ± 5 | 37 ± 2 | 11 ± 5 | 12 ± 5 | 1 | Severe |
| G818E | ER | 51 ± 13 | 63 ± 5 | 111 ± 8 | 25 ± 3 | 12 ± 3 | 2 | Moderate /Severe |
| W821R | ER | 51 ± 6 | 58 ± 7 | 125 ± 7 | 19 ± 8 | 17 ± 6 | 2 | Moderate /Severe |
| I824T | ER | 41 ± 17 | 64 ± 3 | 145 ± 6 | 33 ± 2 | 13 ± 4 | 2 | Moderate /Severe |
| M840R | ER | 26 ± 4 | 37 ± 12 | 47 ± 14 | 12 ± 2 | 14 ± 2 | 1 | Severe |
| D846H | ER | 30 ± 9 | 42 ± 22 | 50 ± 18 | 13 ± 12 | 14 ± 7 | 1 | Severe |
| V849A | Vesicles/ER | 88 ± 20 | 86 ± 5 | 216 ± 13 | 51 ± 12 | 12 ± 9 | 3 | Mild |
| G851D | ER | 27 ± 11 | 31 ± 11 | 46 ± 12 | 13 ± 8 | 12 ± 10 | 1 | Severe |
| A854T | Vesicles/ER | 82 ± 6 | 70 +/−10 | 148 ± 26 | 60 ± 5 | 21 ± 9 | 2 | Moderate |
Values % WT ABCA4; * Placed in Class 2 (Moderate/Mild) due to low N-Ret-PE binding; Data: mean ± SD. * Classification is based equally on the relative expression and substrate-activated ATPase. For more details, see reference [19].