Table 2.
Non-synonymous CUZD1 variants in Japanese subjects with non-alcoholic CP and controls
| Exon | Nucleotide change | Amino acid change | rs number | SIFT | CADD | PROVEAN | PredictSNP | Secretion (% of WT) | CP (n=297) n (%) | Controls (n=1,070) n (%) | p-value |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 2 | c.93C>G | p.S31R* | rs34246902 | 0.25 | 13.0 | Neutral | Neutral | 88* | 30 (10.1) | 87 (8.13) | 0.29 |
| 2 | c.129G>T | p.E43D* | rs35299879 | 0.63 | 9.2 | Neutral | Neutral | 88* | 30 (10.1) | 87 (8.13) | 0.29 |
| 2 | c.163A>G | p.S55G | rs141881176 | 0.02 | 22.1 | Neutral | Neutral | 97 | 7 (2.36) | 18 (1.68) | 0.46 |
| 3 | c.332A>G | p.D111G | rs143659470 | 0.1 | 20.9 | Neutral | Neutral | 95 | 0 | 1 (0.09) | 1.0 |
| 5 | c.607A>G | p.I203V | rs762712325 | 1 | 0.1 | Neutral | Neutral | 93 | 0 | 3 (0.28) | 0.36 |
| 5 | c.620G>A | p.C207Y | - | 0 | 23.8 | Deleterious | Deleterious | 18 | 1 (0.34) | 0 | 0.22 |
| 5 | c.692G>A | p.R231H | rs144483251 | 0.51 | 17.3 | Neutral | Neutral | 94 | 1 (0.34) | 1 (0.09) | 0.39 |
| 5 | c.736G>A | p.V246M* | rs117062933 | 0.11 | 22.1 | Neutral | Neutral | 88* | 30 (10.1) | 87 (8.13) | 0.29 |
| 8 | c.1390C>T | p.R464X | rs200662445 | - | 35.0 | - | - | 2 | 0 | 2 (0.19) | 1.0 |
| 8 | c.1532G>A | p.R511H | rs201005450 | 0 | 31.0 | Deleterious | Deleterious | 84 | 0 | 2 (0.19) | 1.0 |
| 8 | c.1616G>A | p.R539H | rs34962077 | 0.05 | 22.9 | Neutral | Neutral | 89 | 1 (0.34) | 0 | 0.22 |
| 8 | c.1625G>A | p.R542K | rs144406058 | 0.32 | 15.0 | Neutral | Neutral | 96 | 3 (1.01) | 3 (0.28) | 0.12 |
| 9 | c.1787G>A | p.R596Q | rs200173778 | 0.37 | 11.8 | Neutral | Neutral | 106 | 0 | 1 (0.09) | 1.0 |
| Subjects carrying predicted deleterious CUZD1 variants (%) | |||||||||||
| SIFT | 9 (3.0) | 22 (2.1) | 0.38 | ||||||||
| CADD score ≥25 | 0 | 4 (0.4) | 0.58 | ||||||||
| PROVEAN | 1 (0.3) | 4 (0.4) | 1.0 | ||||||||
| PredictSNP | 1 (0.3) | 4 (0.4) | 1.0 | ||||||||
| All (SIFT-CADD25-PROVEAN-PredictSNP) | 0 | 4 (0.4) | 0.58 | ||||||||
| All (SIFT-CADD20-PROVEAN-PredictSNP) | 1 (0.3) | 2 (0.2) | 0.52 | ||||||||
| Secretion <50% | 1 (0.3) | 2 (0.2) | 0.52 | ||||||||
*
These three variants are in complete linkage disequilibrium. Two controls were homozygous. Secretion value of the triple mutant.
CUZD1 variants with a deleterious prediction or less than 50% secretion are in bold. P-values were determined by two-tailed Fisher’s exact test.
Percent secretion are means of two densitometric measurements from two independent Western blots.