Disease Clusters?
Groups of diseases that share a large number of curated genes with each other, computed via label propagation over the shared-gene similarity graph. See also Shared-Gene Disease Pairs for pairwise comparisons.
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Cluster 179
8
Diseases
5
Unique genes
0.387
Avg. similarity score
Dystransthyretinemic euthyroidal hyperthyroxinemia
Most-connected disease (6 links)
Disease
Searched: Thyroid hormone metabolism disorder
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Thyroid hormone metabolism disorder
Dystransthyretinemic euthyroidal hyperthyroxinemia
Hyperthyroxinemia
Senile systemic amyloidosis
Transthyretin amyloid cardiomyopathy
Wild-type transthyretin-related amyloidosis
obsolete hereditary ATTR amyloidosis
Amyloid polyneuropathy
Member diseases (most connected first ‐ the cluster's core)
| Disease ⇵ | Connections in cluster ⇵ | Significant partners ⇵ | Curated genes ⇵ |
|---|---|---|---|
| Dystransthyretinemic euthyroidal hyperthyroxinemia | 6 | 6 | 1 |
| Hyperthyroxinemia | 6 | 6 | 3 |
| Senile systemic amyloidosis | 6 | 6 | 1 |
| Transthyretin amyloid cardiomyopathy | 6 | 6 | 1 |
| Wild-type transthyretin-related amyloidosis | 6 | 6 | 1 |
| obsolete hereditary ATTR amyloidosis | 6 | 6 | 1 |
| Amyloid polyneuropathy | 5 | 5 | 2 |
| Thyroid hormone metabolism disorder | 1 | 1 | 2 |
Top shared genes (genes linked to 2+ member diseases)
| Gene ⇵ | Member diseases ⇵ | Linked diseases |
|---|---|---|
| TTR | 7 / 8 | Amyloid polyneuropathy, Dystransthyretinemic euthyroidal hyperthyroxinemia, Hyperthyroxinemia, obsolete hereditary ATTR amyloidosis and 3 more |
| DIO1 | 2 / 8 | Hyperthyroxinemia, Thyroid hormone metabolism disorder |
What do these columns mean?
- Connections in cluster
- How many other members this disease has a shared-gene link to (the node size in the network above). The most-connected diseases are the cluster's core.
- Significant partners
- How many of those links are statistically significant (FDR q < 0.05).
- Curated genes
- Distinct curated genes linked to that disease in GeDiPNet.
- Member diseases (Top shared genes)
- How many of this cluster's diseases are linked to the gene, out of the cluster's total. Genes shared by many members are the most direct explanation of why they group together.
- Overlap genes (x / y)
- x = genes shared between this cluster and the pathway/GO term; y = that pathway/GO term's total gene count. A higher x relative to y (and to the cluster's own size) means a tighter biological match.
- Cluster gene count
- Total distinct genes across every disease in this cluster -- the "n" used in the significance test below.
- Fold enrichment
- Observed overlap divided by the overlap expected by chance, given the cluster's gene count, the pathway/term's size and the gene universe tested. 5× means five times more shared genes than random. Tells strong hits apart when q-values are all vanishingly small.
- P-value / FDR q-value
- Is this pathway/GO term's overlap with the cluster more than chance? Upper-tail hypergeometric test, Benjamini-Hochberg corrected across every tested pathway/term (prefer the q-value -- it accounts for testing many at once).
- Shared genes (Pairs within this cluster)
- Number of curated genes the two diseases in that row have in common.
- Similarity score (Pairs within this cluster)
- Jaccard-based gene overlap between the two specific diseases in that row -- same metric as the main Shared-Gene Disease Pairs page.
Enriched Pathways (why this cluster is grouped, biologically)
| Pathway ⇵ | Source ⇵ | Overlap genes ⇵ | Fold enrichment ⇵ | P-value ⇵ | FDR q-value ⇵ |
|---|---|---|---|---|---|
| HDL remodeling | Reactome | 2 / 10 | 480× | 6.23e-6 | 2.19e-4 ✓ sig. |
| Scavenging of heme from plasma | Reactome | 2 / 13 | 370× | 1.08e-5 | 3.47e-4 ✓ sig. |
| Retinoid metabolism and transport | Reactome | 2 / 41 | 117× | 1.13e-4 | 2.41e-3 ✓ sig. |
| Thyroid hormone synthesis | KEGG | 2 / 75 | 64.1× | 3.80e-4 | 6.37e-3 ✓ sig. |
| Post-translational protein phosphorylation | Reactome | 2 / 108 | 44.5× | 7.87e-4 | 1.12e-2 ✓ sig. |
| Amyloid fiber formation | Reactome | 2 / 109 | 44.1× | 8.02e-4 | 1.13e-2 ✓ sig. |
| Defective ABCA1 causes Tangier disease | Reactome | 1 / 2 | 1,201× | 8.33e-4 | 1.16e-2 ✓ sig. |
| Platelet degranulation | Reactome | 2 / 123 | 39.1× | 1.02e-3 | 1.36e-2 ✓ sig. |
| Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) | Reactome | 2 / 125 | 38.4× | 1.05e-3 | 1.40e-2 ✓ sig. |
| Regulation of thyroid hormone activity | Reactome | 1 / 3 | 801× | 1.25e-3 | 1.59e-2 ✓ sig. |
| HDL clearance | Reactome | 1 / 5 | 480× | 2.08e-3 | 2.34e-2 ✓ sig. |
| Scavenging by Class B Receptors | Reactome | 1 / 5 | 480× | 2.08e-3 | 2.34e-2 ✓ sig. |
| HDL assembly | Reactome | 1 / 8 | 300× | 3.33e-3 | 3.29e-2 ✓ sig. |
| Chylomicron remodeling | Reactome | 1 / 9 | 267× | 3.74e-3 | 3.58e-2 ✓ sig. |
| Chylomicron assembly | Reactome | 1 / 9 | 267× | 3.74e-3 | 3.58e-2 ✓ sig. |
Enriched GO Terms (Biological Process, a second line of biological evidence)
| GO term ⇵ | GO ID ⇵ | Overlap genes ⇵ | Fold enrichment ⇵ | P-value ⇵ | FDR q-value ⇵ |
|---|---|---|---|---|---|
| thyroid hormone catabolic process | GO:0042404 | 1 / 3 | 1,246× | 8.03e-4 | 1.32e-2 ✓ sig. |
| protein oxidation | GO:0018158 | 1 / 3 | 1,246× | 8.03e-4 | 1.32e-2 ✓ sig. |
| peptidyl-methionine modification | GO:0018206 | 1 / 3 | 1,246× | 8.03e-4 | 1.32e-2 ✓ sig. |
| positive regulation of phospholipid efflux | GO:1902995 | 1 / 4 | 934× | 1.07e-3 | 1.58e-2 ✓ sig. |
| negative regulation of glomerular filtration | GO:0003105 | 1 / 4 | 934× | 1.07e-3 | 1.58e-2 ✓ sig. |
| cellular response to calcium ion starvation | GO:0072732 | 1 / 4 | 934× | 1.07e-3 | 1.58e-2 ✓ sig. |
| regulation of intestinal cholesterol absorption | GO:0030300 | 1 / 4 | 934× | 1.07e-3 | 1.58e-2 ✓ sig. |
| cellular response to lipoprotein particle stimulus | GO:0071402 | 1 / 5 | 747× | 1.34e-3 | 1.81e-2 ✓ sig. |
| acylglycerol homeostasis | GO:0055090 | 1 / 5 | 747× | 1.34e-3 | 1.81e-2 ✓ sig. |
| lipoprotein biosynthetic process | GO:0042158 | 1 / 6 | 623× | 1.60e-3 | 2.01e-2 ✓ sig. |
| cholesterol import | GO:0070508 | 1 / 6 | 623× | 1.60e-3 | 2.01e-2 ✓ sig. |
| negative regulation of very-low-density lipoprotein particle remodeling | GO:0010903 | 1 / 6 | 623× | 1.60e-3 | 2.01e-2 ✓ sig. |
| purine nucleobase metabolic process | GO:0006144 | 1 / 7 | 534× | 1.87e-3 | 2.22e-2 ✓ sig. |
| positive regulation of cholesterol metabolic process | GO:0090205 | 1 / 7 | 534× | 1.87e-3 | 2.22e-2 ✓ sig. |
| high-density lipoprotein particle clearance | GO:0034384 | 1 / 7 | 534× | 1.87e-3 | 2.22e-2 ✓ sig. |