Data from expression studies
. | . | . | . | . | . | . | Proteolysis full-length rhuVWF‡ . | . | Proteolysis rhuVWFA1-A2-A3 . | . | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mutation . | Group* . | Cell-lysate VWF/Ag, % WT† . | SD, % . | Medium VWF/Ag, % WT† . | SD, % . | Ratio medium: cell-lysate . | + Urea . | - Urea . | + Urea . | - Urea . | ||
| WT | 100.0 | 1.0 | 100.0 | 1.2 | 1.00 | Cleavage | Cleavage | Yes | No | |||
| C1272S§ | 1 | 98.1 | 3.5 | 40.9 | 4.1 | 0.42 | - | ++ | No | No | ||
| C1272S + WT§ | 1 | 82.7 | 1.1 | 71.0 | 1.5 | 0.86 | - | + | NA | NA | ||
| G1505E | 2 | 53.4 | 3.2 | 72.6 | 1.5 | 1.36 | = | = | Yes | Yes | ||
| G1505E + WT | 2 | 87.5 | 2.8 | 89.7 | 2.9 | 1.02 | - | - | NA | NA | ||
| G1505R | 1 | 58.8 | 3.6 | 8.2 | 2.1 | 0.14 | ++ | ++ | Yes | Yes | ||
| G1505R + WT | 1 | 74.8 | 2.5 | 50.6 | 1.7 | 0.67 | - | + | NA | NA | ||
| S1506L | 1 | 20.9 | 1.7 | 1.3 | 0.5 | 0.06 | ++ | ++ | Yes | No | ||
| S1506L + WT | 1 | 68.1 | 0.2 | 40.3 | 1.6 | 0.59 | = | + | NA | NA | ||
| M1528V§ | 2 | 75.9 | 3.8 | 86.3 | 1.3 | 1.14 | + | ++ | Yes | No | ||
| M1528V + WT§ | 2 | 86.7 | 3.0 | 77.2 | 1.8 | 0.89 | - | + | NA | NA | ||
| Del R1569§ | 1 | 27.1 | 1.3 | 0.9 | 0.02 | 0.03 | ++ | ++ | NA | NA | ||
| Del R1569 + WT§ | 1 | 67.5 | 1.1 | 46.8 | 1.6 | 0.69 | - | - | NA | NA | ||
| R1597W | 2 | 94.0 | 4.2 | 81.7 | 5.0 | 0.87 | ++ | ++ | Yes | No | ||
| R1597W + WT | 2 | 68.6 | 3.4 | 80.3 | 1.2 | 1.17 | + | + | NA | NA | ||
| V1607D | 1 | 47.0 | 2.4 | 0.1 | 0.0 | 0.00 | ++ | ++ | NA | NA | ||
| V1607D + WT | 1 | 66.8 | 1.8 | 35.7 | 2.0 | 0.53 | - | + | NA | NA | ||
| G1609R | 2 | 30.0 | 0.9 | 84.4 | 2.2 | 2.81 | ++ | ++ | Yes | Yes | ||
| G1609R + WT | 2 | 70.7 | 1.7 | 118.0 | 1.2 | 1.67 | + | + | NA | NA | ||
| I1628T | 2 | 103.3 | 4.5 | 87.5 | 2.1 | 0.85 | (-) | - | Yes | Yes | ||
| I1628T + WT | 2 | 95.0 | 2.7 | 89.0 | 1.8 | 0.94 | = | - | NA | NA | ||
| G1629E§ | 2 | 43.2 | 2.7 | 78.5 | 3.0 | 1.82 | ++ | +++ | Yes | Yes | ||
| G1629E + WT§ | 2 | 56.7 | 3.0 | 90.9 | 0.3 | 1.60 | + | ++ | NA | NA | ||
| G1631D§ | 2 | 60.4 | 3.4 | 63.7 | 1.2 | 1.06 | ++ | ++ | Yes | Yes | ||
| G1631D + WT§ | 2 | 72.1 | 1.6 | 66.7 | 2.1 | 0.93 | = | + | NA | NA | ||
| E1638K | 2 | 77.6 | 0.9 | 79.1 | 2.1 | 1.02 | ++ | ++ | Yes | No | ||
| E1638K + WT | 2 | 87.5 | 2.5 | 84.6 | 3.0 | 0.97 | + | + | NA | NA | ||
. | . | . | . | . | . | . | Proteolysis full-length rhuVWF‡ . | . | Proteolysis rhuVWFA1-A2-A3 . | . | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mutation . | Group* . | Cell-lysate VWF/Ag, % WT† . | SD, % . | Medium VWF/Ag, % WT† . | SD, % . | Ratio medium: cell-lysate . | + Urea . | - Urea . | + Urea . | - Urea . | ||
| WT | 100.0 | 1.0 | 100.0 | 1.2 | 1.00 | Cleavage | Cleavage | Yes | No | |||
| C1272S§ | 1 | 98.1 | 3.5 | 40.9 | 4.1 | 0.42 | - | ++ | No | No | ||
| C1272S + WT§ | 1 | 82.7 | 1.1 | 71.0 | 1.5 | 0.86 | - | + | NA | NA | ||
| G1505E | 2 | 53.4 | 3.2 | 72.6 | 1.5 | 1.36 | = | = | Yes | Yes | ||
| G1505E + WT | 2 | 87.5 | 2.8 | 89.7 | 2.9 | 1.02 | - | - | NA | NA | ||
| G1505R | 1 | 58.8 | 3.6 | 8.2 | 2.1 | 0.14 | ++ | ++ | Yes | Yes | ||
| G1505R + WT | 1 | 74.8 | 2.5 | 50.6 | 1.7 | 0.67 | - | + | NA | NA | ||
| S1506L | 1 | 20.9 | 1.7 | 1.3 | 0.5 | 0.06 | ++ | ++ | Yes | No | ||
| S1506L + WT | 1 | 68.1 | 0.2 | 40.3 | 1.6 | 0.59 | = | + | NA | NA | ||
| M1528V§ | 2 | 75.9 | 3.8 | 86.3 | 1.3 | 1.14 | + | ++ | Yes | No | ||
| M1528V + WT§ | 2 | 86.7 | 3.0 | 77.2 | 1.8 | 0.89 | - | + | NA | NA | ||
| Del R1569§ | 1 | 27.1 | 1.3 | 0.9 | 0.02 | 0.03 | ++ | ++ | NA | NA | ||
| Del R1569 + WT§ | 1 | 67.5 | 1.1 | 46.8 | 1.6 | 0.69 | - | - | NA | NA | ||
| R1597W | 2 | 94.0 | 4.2 | 81.7 | 5.0 | 0.87 | ++ | ++ | Yes | No | ||
| R1597W + WT | 2 | 68.6 | 3.4 | 80.3 | 1.2 | 1.17 | + | + | NA | NA | ||
| V1607D | 1 | 47.0 | 2.4 | 0.1 | 0.0 | 0.00 | ++ | ++ | NA | NA | ||
| V1607D + WT | 1 | 66.8 | 1.8 | 35.7 | 2.0 | 0.53 | - | + | NA | NA | ||
| G1609R | 2 | 30.0 | 0.9 | 84.4 | 2.2 | 2.81 | ++ | ++ | Yes | Yes | ||
| G1609R + WT | 2 | 70.7 | 1.7 | 118.0 | 1.2 | 1.67 | + | + | NA | NA | ||
| I1628T | 2 | 103.3 | 4.5 | 87.5 | 2.1 | 0.85 | (-) | - | Yes | Yes | ||
| I1628T + WT | 2 | 95.0 | 2.7 | 89.0 | 1.8 | 0.94 | = | - | NA | NA | ||
| G1629E§ | 2 | 43.2 | 2.7 | 78.5 | 3.0 | 1.82 | ++ | +++ | Yes | Yes | ||
| G1629E + WT§ | 2 | 56.7 | 3.0 | 90.9 | 0.3 | 1.60 | + | ++ | NA | NA | ||
| G1631D§ | 2 | 60.4 | 3.4 | 63.7 | 1.2 | 1.06 | ++ | ++ | Yes | Yes | ||
| G1631D + WT§ | 2 | 72.1 | 1.6 | 66.7 | 2.1 | 0.93 | = | + | NA | NA | ||
| E1638K | 2 | 77.6 | 0.9 | 79.1 | 2.1 | 1.02 | ++ | ++ | Yes | No | ||
| E1638K + WT | 2 | 87.5 | 2.5 | 84.6 | 3.0 | 0.97 | + | + | NA | NA | ||
SD indicates standard deviation; NA, not applicable; +, increased proteolysis compared with rhuVWF-WT; ++, strongly increased proteolysis compared with rhuVWF-WT; +++, very strongly increased proteolysis compared with rhuVWF-WT; -, reduced proteolysis compared with rhuVWF-WT; (-), moderately reduced proteolysis compared with rhuVWF-WT; =, proteolysis equal to rhuVWF-WT.
Group classification according to Lyons et al16 (1 indicates decreased expression; 2, increased cleavage).
Expression experiments were done in triplicate; data represent mean values.
Cleavage of recombinant human VWF (rhuVWF) mutants was assessed in comparison with rhuVWF-WT digested under the same conditions.
Novel mutations.