Table 2. Genes with LoF variants — summary of predicted gene product function and location using gene ontology terms and pathway analysis.
| Pathway name | Pathway source | Total set size | No. of identified genes | P-value | q-value | Description |
|---|---|---|---|---|---|---|
| Over-represented pathwaysa | ||||||
| CYP2E1 reactions | Reactome | 11 | 6 (54.5%) | 0.00004 | 0.0518 | Xenobiotics related |
| Leukotriene metabolism | EHMN | 104 | 19 (18.3%) | 9.89 × 10−5 | 0.0518 | Lipid metabolism |
| Galactose metabolism | KEGG | 30 | 9 (30.0%) | 0.000148 | 0.0518 | Other |
| Tryptophan degradation | INOH | 66 | 14 (21.2%) | 0.000158 | 0.0518 | Xenobiotics relatedb |
| Metabolism of xenobiotics by cytochrome P450 | KEGG | 74 | 15 (20.3%) | 0.000159 | 0.0518 | Xenobiotics related |
| Androgen and oestrogen biosynthesis and metabolism | EHMN | 87 | 16 (18.4%) | 0.000318 | 0.0789 | Lipid metabolism |
| Fatty acids | Reactome | 15 | 6 (40.0%) | 0.000339 | 0.0789 | Lipid metabolism |
| Xenobiotics | Reactome | 21 | 7 (33.3%) | 0.000398 | 0.0803 | Xenobiotics related |
| Chemical carcinogenesis | KEGG | 81 | 15 (18.5%) | 0.000448 | 0.0803 | Xenobiotics related |
| C21-steroid hormone biosynthesis and metabolism | EHMN | 57 | 12 (21.1%) | 0.000493 | 0.0803 | Lipid metabolism |
| GO term | Total set size | No. of identified genes | P-value | q-value |
|---|---|---|---|---|
| Over-represented GO termsb | ||||
| GO group: Molecular function | ||||
| GO:0043167 ion binding | 6117 | 531 (8.7%) | 8.85 × 10−8 | 4.6 × 10−6 |
| GO:0016787 hydrolase activity | 2477 | 235 (9.5%) | 3.66 × 10−6 | 9.51 × 10−5 |
| GO:0016491 oxidoreductase activity | 728 | 77 (10.6%) | 0.000529 | 0.00917 |
| GO:0019825 oxygen binding | 47 | 9 (19.1%) | 0.00601 | 0.071 |
| GO:0030246 carbohydrate binding | 279 | 32 (11.5%) | 0.00683 | 0.071 |
| GO:0004601 peroxidase activity | 41 | 8 (19.5%) | 0.00836 | 0.0724 |
| GO group: Cellular compartment | ||||
| GO:0005929 cilium | 465 | 53 (11.4%) | 0.000719 | 0.0302 |
| GO:0044441 ciliary part | 309 | 38 (12.3%) | 0.000987 | 0.0302 |
| GO:0005578 proteinaceous extracellular matrix | 356 | 42 (11.9%) | 0.00113 | 0.0302 |
| GO:0034358 plasma lipoprotein particle | 39 | 8 (20.5%) | 0.00612 | 0.0926 |
| GO:0005615 extracellular space | 1338 | 120 (9.0%) | 0.00686 | 0.0926 |
| GO:0072562 blood microparticle | 135 | 18 (13.4%) | 0.00821 | 0.0926 |
| GO:0032994 protein–lipid complex | 41 | 8 (19.5%) | 0.00836 | 0.0926 |
| GO:0005604 basement membrane | 97 | 14 (14.6%) | 0.00926 | 0.0926 |
a
Annotations are ordered by q-values.
b
Tryptophan degradation pathway is classified as xenobiotic-related as tryptophan metabolites are known to activate aryl hydrocarbon receptor, transcription factor known to mediate most of the toxic and carcinogenic effects of a wide variety of environmental contaminants.