Table 1.
hPGK1 mutations, their effects on enzyme molecular properties, and clinical features in patients with hPGK1 deficiency.
| Nucleotide Change | Amino Acid Change | a Localization | b Catalytic Properties | c Protein Stability | RBC Residual Activity (%) | Hb (g/dl) | Reticulocytes (%) | d Symptoms | References | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| A | M | N | |||||||||
| c.140 T > A | # p.I47N | α-helix 1b | ○ | ○○○ | 8 | 6.6–7.3 | N.A. | + | - | + | [37] |
| c.266 T > C | # p.L89P | α-helix 2 * | ○ | ○○○ | 5 | N.A. | N.A. | + | - | + | [40] |
| c.473 G > T | # p.G158V | loop α-helix 4, β-strand E | ○○ | ○○ | 1 | 12.8 | 2.5 | - | + | - | [65] |
| c.491 A > T | # p.D164V | β-strand E | ○○○ | ○○○ | 5 | 2.0–10.0 | 5.0-26-0 | + | +/- | + | [36,38,41,66] |
| c.571 > 573 del | # p.K191del | α-helix 7 * | ○○ | ○○ | 4 | 14.1 | 6.4 | - | - | - | [41] |
| c.617 G > C | # p.R206P | loop α-helix 7, β-strand G * | - | ○ | 10 | 5.6–13.7 | 2.0–20.0 | +/- | - | + | [67] |
| c.755 A > C | # p.E252A | loop α-helix 9, α-helix 10 * | - | - | 6 | 13.2 | N.A. | - | + | - | [68] |
| c.758 T > C | # p.I253T | loop α-helix 9, α-helix 10 * | - | - | 8 | N.A. | N.A. | - | + | + | [69] |
| c.796 G > A c.798 C > A |
# p.V266M | α-helix 10a/b | - | - | 10 | 9.3 | 12.5 | + | - | + | [70] |
| c.802 G > A | # p.D268N | α-helix 10b * | - | - | 21 | N.A. | 0.4–1.3 | - | - | - | [71] |
| c.854 A > T | # p.D285V | β-strand o * | ○○ | ○○○ | 49 | 9.0–10.0 | 10–45 | - | - | - | [68] |
| c.943 G > A | # p.D315N | β-strand q | ○○ | ○○○ | 3 | 14.3 | N.A. | - | + | - | [72] |
| c.946 T > C | # p.C316R | β-strand q | ○ | ○○○ | 10 | 7.5-13.0 | 1.5–5.0 | +/- | - | + | [66] |
| c.959 G > A | # p.S320N | α-helix 11 | ○ | ○○○ | 36 | 7.6 | 9.0 | + | - | + | [73] |
| c.1060 G > C | # p.A354P | α-helix 12 * | ○ | ○○○ | 6 | 4.9–9.0 | 24 | + | + | + | [37] |
| c.1112 T > A | # p.I371K | β-strand K | ○○ | ○○ | 12 | 12.1–14.1 | 4.4–5.2 | +/- | + | + | [30] |
| c.1132 A > C | # p.T378P | α-helix 13 * | ○○ | - | 2 | 13.4–14.5 | N.A. | - | + | - | [28,29] |
| IVS4+1 G > T | splicing alteration | 3 | N.A. | 2.7 | - | + | + | [74] | |||
| c.637 > 640 delGGCG | frameshift | 6 | N.A. | N.A. | - | + | - | [75] | |||
| c.639 C > T | splicing alteration | 5 | N.A. | N.A. | - | + | - | [76,77] | |||
| IVS7+5 G > A | splicing alteration | 14 | N.A. | N.A. | - | + | + | [78] | |||
# variants characterized; a according to [59]; * solvent accessible; b catalytic efficiency toward 3-PG or Mg-ATP: ○○○ < 1%; ○○ < 10%; ○ < 25%; - comparable to WT; c heat stability (Tm): ○○○ nearly 10 °C lowered; ○○ nearly 3–7 °C lowered; ○ nearly 2 °C lowered; - comparable to WT; d A: anemia (+/-: compensated hemolytic anemia with occasional hemolytic crises); M: muscular disorders (+/-: sporadic manifestations); N: neurological disorders; N.A.: not available.