Table 5.
Functional characterization of NPR2 nonsynonymous variants in three cohorts
| Variant | Observation | Minor Allele Frequency |
Segregation Within Family |
Relative Guanylyl Cyclase Activities % (±SD) – Enzyme Assay with 1uM CNP |
Relative Guanylyl Cyclase Activities % (±SD) – Whole Cell Lysate |
|---|---|---|---|---|---|
| c.1352-1G>A | Patient 1 | Novel | de novo | N/A | N/A |
| c.142G>T (p.A48S) | Patient 2 | Novel | Yes | 36.6 (14.9)* | 93.5 (15.4) |
| c.1167G>T (p.E389D) | Patient 3 | Novel | Yes | 57.0 (12.0)* | 108.5 (24.6) |
| c.1481T>G (p.I494S) | Patient 4 | Novel | Yes | <6* | 54.3 (8.6)* |
| c.1645G>A (p.A549T) | Patient 5 | Novel | Unknown | 68.7 (26.9) | 111.2 (9.6) |
| rs62637657: c.491C>G (p.A164G) | Patient 6 | 0.02% | No | 25.9 (10.3)* | 130.6 (15.5)* |
| rs114147262: c.2359C>T (p.R787W) | Patient 7 | 0.16% | N/A | 62.8 (36.6) | 90.9 (14.0) |
| c.316G>T (p.A106S) | Patient | Novel | N/A | 83.9 (32.5) | N/A |
| rs180950551: c.1802G>C (p.R601P) | Patient | 0.02% | N/A | 64.5 (12.9) | N/A |
| c.2710A>T (p.K904*) | Patient | Novel | N/A | N/A | N/A |
| rs114115939: c.1517G>A (p.R506H) | Patient | 0.06% | N/A | <6* | N/A |
| c.739A>G (p.N247D) | FINRISK tall extreme (also observed in Estonian tall extreme and short extreme) | Novel | N/A | 69.1 (37.3) | 246.9 (66.5)* |
| c.1685G>A (p.R562Q) | FINRISK tall extreme | Novel | N/A | 145.7 (31.6)* | 711.8 (238.2)* |
| c.2449G>A (p.E817K) | Estonian short extreme | Novel | N/A | N/A | 31.1 (0.3)* |
| c.2338G>A (p.G780R) | Estonian short extreme | Novel | N/A | N/A | 98.3 (11.9) |
| c.1982C>A (p.T661K) | Estonian short extreme | Novel | N/A | N/A | 65.7 (19.1)* |
*
p <0.05.
GenBank reference sequence used for NPR2 is NM_003995.3.