Table 3 Overall impact prediction of Kabuki variants derived from the assessment at each layer. Impact assignment of the variants at each layer are tentatively given by referring to the control values. These data illustrate the multiple pathways these variants may be affecting KDM6A function
Variant | Sequence | Structure | pK Shift | Dynamics | Substrate and Zn interaction | Active site interactions | Overall impact prediction |
|---|---|---|---|---|---|---|---|
H1146A | Damaging | Benign | Damaging | Damaging | Damaging | Damaging | Damaging control |
E1148A | Damaging | Damaging | Damaging | Damaging | Damaging | Damaging | Damaging control |
H1060L | Benign | Benign | Benign | Benign | Benign | Benign | Benign control |
S912N | Benign | Benign | Benign | Benign | Benign | Benign | Benign control |
T1323A | Benign | Benign | Benign | Benign | Benign | Benign | Benign control |
N910S | Benign | Damaging | Benign | Damaging | Benign | VUS | Damaging |
D980V | Damaging | VUS | VUS | Damaging | Benign | Damaging | Damaging |
S1025G | Damaging | VUS | Benign | Damaging | Damaging | VUS | Damaging |
C1153R | Damaging | Damaging | Damaging | Damaging | Damaging | Damaging | Damaging |
C1153Y | Damaging | Damaging | Damaging | Damaging | Damaging | VUS | Damaging |
P1195L | VUS | Damaging | Damaging | Damaging | Damaging | VUS | Damaging |
L1200F | Damaging | Damaging | Damaging | Damaging | Benign | Benign | Damaging |
Q1212R | Damaging | Damaging | Damaging | Damaging | Damaging | VUS | Damaging |
Q1248R | Damaging | Damaging | Damaging | Damaging | Damaging | VUS | Damaging |
R1255W | Damaging | Damaging | Damaging | Damaging | Damaging | Damaging | Damaging |
R1351Q | Benign | Damaging | Damaging | Damaging | Damaging | VUS | Damaging |