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 435
6
Diseases
9
Unique genes
0.216
Avg. similarity score
Amme complex
Most-connected disease (4 links)
Disease
Searched: Non-syndromic X-linked intellectual disability
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Non-syndromic X-linked intellectual disability
Amme complex
Alport syndrome with mental retardation midface hypoplasia and elliptocytosis
Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome
Fraxe intellectual disability
Midface hypoplasia-hearing impairment-elliptocytosis-nephrocalcinosis syndrome
Member diseases (most connected first ‐ the cluster's core)
| Disease ⇵ | Connections in cluster ⇵ | Significant partners ⇵ | Curated genes ⇵ |
|---|---|---|---|
| Amme complex | 4 | 4 | 3 |
| Non-syndromic X-linked intellectual disability | 4 | 4 | 7 |
| Alport syndrome with mental retardation midface hypoplasia and elliptocytosis | 3 | 3 | 1 |
| Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome | 3 | 3 | 1 |
| Fraxe intellectual disability | 1 | 1 | 1 |
| Midface hypoplasia-hearing impairment-elliptocytosis-nephrocalcinosis syndrome | 1 | 1 | 1 |
Top shared genes (genes linked to 2+ member diseases)
| Gene ⇵ | Member diseases ⇵ | Linked diseases |
|---|---|---|
| ACSL4 | 4 / 6 | Alport syndrome with mental retardation midface hypoplasia and elliptocytosis, Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome, Amme complex, Non-syndromic X-linked intellectual disability |
| AFF2 | 2 / 6 | Fraxe intellectual disability, Non-syndromic X-linked intellectual disability |
| AMMECR1 | 2 / 6 | Amme complex, Midface hypoplasia-hearing impairment-elliptocytosis-nephrocalcinosis syndrome |
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 ⇵ |
|---|---|---|---|---|---|
| Intracellular metabolism of fatty acids regulates insulin secretion | Reactome | 1 / 3 | 445× | 2.25e-3 | 1.98e-2 ✓ sig. |
| Phase 3 - rapid repolarisation | Reactome | 1 / 8 | 167× | 5.98e-3 | 3.93e-2 ✓ sig. |
| Activation of Ca-permeable Kainate Receptor | Reactome | 1 / 12 | 111× | 8.96e-3 | 5.11e-2 |
| Trafficking of GluR2-containing AMPA receptors | Reactome | 1 / 17 | 78.5× | 1.27e-2 | 6.36e-2 |
| Fatty acid biosynthesis | KEGG | 1 / 18 | 74.1× | 1.34e-2 | 6.57e-2 |
| Synaptic adhesion-like molecules | Reactome | 1 / 21 | 63.5× | 1.56e-2 | 7.23e-2 |
| Unblocking of NMDA receptors, glutamate binding and activation | Reactome | 1 / 22 | 60.7× | 1.64e-2 | 7.41e-2 |
| Synthesis of very long-chain fatty acyl-CoAs | Reactome | 1 / 22 | 60.7× | 1.64e-2 | 7.41e-2 |
| Phase 2 - plateau phase | Reactome | 1 / 25 | 53.4× | 1.86e-2 | 7.99e-2 |
| Neurexins and neuroligins | Reactome | 1 / 32 | 41.7× | 2.37e-2 | 9.26e-2 |
| Ferroptosis | KEGG | 1 / 42 | 31.8× | 3.10e-2 | 1.08e-1 |
| Fatty acid degradation | KEGG | 1 / 43 | 31.0× | 3.18e-2 | 1.10e-1 |
| Fatty acid metabolism | KEGG | 1 / 57 | 23.4× | 4.19e-2 | 1.29e-1 |
| Adipocytokine signaling pathway | KEGG | 1 / 70 | 19.1× | 5.13e-2 | 1.45e-1 |
| PPAR signaling pathway | KEGG | 1 / 76 | 17.6× | 5.56e-2 | 1.52e-1 |
Enriched GO Terms (Biological Process, a second line of biological evidence)
| GO term ⇵ | GO ID ⇵ | Overlap genes ⇵ | Fold enrichment ⇵ | P-value ⇵ | FDR q-value ⇵ |
|---|---|---|---|---|---|
| negative regulation of prostaglandin secretion | GO:0032307 | 1 / 1 | 2,076× | 4.82e-4 | 9.07e-3 ✓ sig. |
| regulation of opioid receptor signaling pathway | GO:2000474 | 1 / 2 | 1,038× | 9.63e-4 | 1.40e-2 ✓ sig. |
| nuclear speck organization | GO:0035063 | 1 / 4 | 519× | 1.93e-3 | 2.04e-2 ✓ sig. |
| synaptic vesicle membrane organization | GO:0048499 | 1 / 5 | 415× | 2.41e-3 | 2.30e-2 ✓ sig. |
| regulation of atrial cardiac muscle cell membrane repolarization | GO:0060372 | 1 / 6 | 346× | 2.89e-3 | 2.52e-2 ✓ sig. |
| negative regulation of protein targeting to membrane | GO:0090315 | 1 / 6 | 346× | 2.89e-3 | 2.52e-2 ✓ sig. |
| positive regulation of toll-like receptor signaling pathway | GO:0034123 | 1 / 6 | 346× | 2.89e-3 | 2.52e-2 ✓ sig. |
| negative regulation of protein localization | GO:1903828 | 1 / 6 | 346× | 2.89e-3 | 2.52e-2 ✓ sig. |
| negative regulation of potassium ion export across plasma membrane | GO:1903765 | 1 / 6 | 346× | 2.89e-3 | 2.52e-2 ✓ sig. |
| long-chain fatty-acyl-CoA metabolic process | GO:0035336 | 1 / 7 | 297× | 3.37e-3 | 2.73e-2 ✓ sig. |
| negative regulation of mitochondrial fusion | GO:0010637 | 1 / 8 | 260× | 3.85e-3 | 2.90e-2 ✓ sig. |
| negative regulation of peroxisome proliferator activated receptor signaling pathway | GO:0035359 | 1 / 8 | 260× | 3.85e-3 | 2.90e-2 ✓ sig. |
| embryonic process involved in female pregnancy | GO:0060136 | 1 / 8 | 260× | 3.85e-3 | 2.90e-2 ✓ sig. |
| receptor localization to synapse | GO:0097120 | 1 / 9 | 231× | 4.33e-3 | 3.08e-2 ✓ sig. |
| atrial cardiac muscle cell action potential | GO:0086014 | 1 / 9 | 231× | 4.33e-3 | 3.08e-2 ✓ sig. |