TABLE 5.
In silico predictions of putative effects of non-synonymous variants on protein structure. The effect predictions were obtained with the CUPSAT tool (Parthiban et al., 2006) utilizing the protein structures of CKB (PBD ID: 3DRE; Bong et al., 2008), CKMT1B (PBD ID:1QK1; Eder et al., 2000) and GATM (PBD ID: 2JDW; Humm et al., 1997) and the PANTHER-PSEP tool (Tang and Thomas, 2016). As no full-length PBD protein structure was available for CKMT1B, we could not determine the impact of rs149544188 (a). As only non-synonymous variants could be predicted, the non-sense variant rs1230355611 (p. Arg184Stop) in CKMT1B was not analysed.
| Gene | Variant | Amino acid exchange | Cupsat | Panther-PSEP | ||||
|---|---|---|---|---|---|---|---|---|
| Protein stability | Protein torsion | ΔΔG (kcal/mol) | Preservation time | Prediction | Probability of a deleterious effect | |||
| CKB | rs146047573 | Tyr269Cys | Destabilizing | Favorable | −2.93 | 361 | Possibly damaging | 0.5 |
| CKMT1B | rs758572075 | Val191Arg | Stabilizing | Favorable | 0.96 | 324 | Possibly damaging | 0.5 |
| rs149544188a | Arg399His | NA a | NA a | NA a | 361 | Possibly damaging | 0.5 | |
| GATM | rs1288775 | Gln110His | Destabilizing | Favorable | −0.3 | 6 | Probably benign | 0.02 |
| rs146057680 | Asp234Val | Destabilizing | Favorable | −1.21 | 1,368 | Probably damaging | 0.86 | |
| rs773358289 | Pro287Ser | Destabilizing | Favorable | −0.81 | 797 | Probably damaging | 0.74 | |
| rs747005297 | His292Arg | Stabilizing | Unfavorable | 0.06 | 3,806 | Probably damaging | 0.89 | |