Table 2.
Predicted structural effects of known PRPS1 mutations
| Mutation | Disturbance of local structure | Affecting dimer interface | Affecting trimer interface | Disturbance of ATP binding site | Disturbance of allosteric site I | Disturbance of allosteric site II | Neuropathy |
|---|---|---|---|---|---|---|---|
|
PRS-I superactivity |
|
|
|
|
|
|
|
| p.D52H |
+ |
- |
+ |
- |
+ |
- |
- |
| p.N114S |
- |
+ |
+ |
- |
+/- |
+/- |
+ |
| p.L129I |
+ |
- |
- |
- |
- |
+ |
+ |
| p.D183H |
- |
+ |
- |
- |
+/- |
+/- |
+ |
| p.A190V |
+ |
+ |
- |
- |
+/- |
+/- |
+ |
| p.H193L** |
- |
+ |
- |
- |
+/- |
+/- |
- |
| p.H193Q |
- |
+ |
- |
- |
+/- |
+/- |
+ |
| p.V142L |
+ |
+ |
- |
- |
- |
+ |
+ |
|
Arts syndrome |
|
|
|
|
|
|
|
| p.Q133P |
+ |
+ |
- |
+ |
+/- |
+ |
+ |
| p.L152P |
+ |
+ |
- |
+ |
+/- |
+ |
+ |
|
p.Q277P |
+ |
- |
+/- |
+ |
- |
- |
+ |
|
CMTX5 |
|
|
|
|
|
|
|
| p.E43D |
- |
- |
+ |
+ |
+ |
- |
+ |
| p.M115T |
- |
- |
+ |
+ |
+ |
- |
+ |
| p.A121G |
+ |
- |
+/- |
+/- |
+/- |
- |
+ |
|
DFN2 |
|
|
|
|
|
|
|
| p.D65N |
- |
- |
+ |
- |
- |
- |
? |
| p.A87T |
+ |
- |
- |
- |
- |
- |
? |
| p.I290T |
+ |
- |
- |
- |
- |
- |
? |
| p.G306R | - | - | + | - | - | - | ? |
When comparing the protein structural effects of all known PRPS1 mutations and their relations to PRPS1-phenotypic clusters, the p.Gln277Pro mutation falls in between CMTX5 and Arts syndrome PRPS1 mutations. Like other Arts syndrome mutations (and in contrast to CMTX5 PRPS1 mutations), it is predicted to disrupt the local PRS-I structure. However, unlike the other Arts syndrome mutations (and in line with other CMTX PRPS1 mutations), it is not predicted to disturb the allosteric site II or to affect the dimer interface. This table was selected, updated and extended from de Brouwer et al., 2010 [6]. Please see here also for further references [6]. **This mutation was found in a female patient.