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 290

6 diseases · 9 shared-gene connections
6 Diseases
19 Unique genes
0.240 Avg. similarity score
Rhabdomyolysis Most-connected disease (5 links)
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Disease Searched: Asymptomatic hyperckemia-myalgia-rhabdomyolysis syndrome Pinned (dragged)
Node size = connections within this cluster · edge thickness = similarity strength · hover an edge for its details · click a node to select it and show its pairs below (double-click or Ctrl/⌘-click opens the disease page) · drag a node to pin it in place · scroll/pinch to zoom.

Member diseases (most connected first ‐ the cluster's core)

Disease ⇵ Connections in cluster ⇵ Significant partners ⇵ Curated genes ⇵
Rhabdomyolysis 5 5 8
Asymptomatic hyperckemia-myalgia-rhabdomyolysis syndrome 3 3 1
Distal anoctaminopathy 3 3 1
gnathodiaphyseal dysplasia 3 3 1
Acrokeratosis verruciformis 2 2 1
Diabetic cardiomyopathy 2 2 14

Top shared genes (genes linked to 2+ member diseases)

Gene ⇵ Member diseases ⇵ Linked diseases
ANO5 4 / 6 Asymptomatic hyperckemia-myalgia-rhabdomyolysis syndrome, Distal anoctaminopathy, gnathodiaphyseal dysplasia, Rhabdomyolysis
ATP2A2 3 / 6 Acrokeratosis verruciformis, Diabetic cardiomyopathy, Rhabdomyolysis
INS 2 / 6 Diabetic cardiomyopathy, Rhabdomyolysis
RYR2 2 / 6 Diabetic cardiomyopathy, Rhabdomyolysis
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 ⇵
Hypertrophic cardiomyopathy
ATP2A2, AGT, IGF1, RYR2, TNF
 KEGG 5 / 99 31.9× 3.65e-7 2.17e-5 ✓ sig.
Dilated cardiomyopathy
ATP2A2, AGT, IGF1, RYR2, TNF
 KEGG 5 / 105 30.1× 4.90e-7 2.81e-5 ✓ sig.
Renin-angiotensin system
AGT, AGTR2, KLK1
 KEGG 3 / 23 82.4× 5.83e-6 2.29e-4 ✓ sig.
Diabetic cardiomyopathy
ATP2A2, AGT, INS, RYR2, SLC25A4
 KEGG 5 / 205 15.4× 1.32e-5 4.46e-4 ✓ sig.
Hormone signaling
AGT, AGTR2, IGF1, INS, LEPR
 KEGG 5 / 219 14.4× 1.82e-5 5.82e-4 ✓ sig.
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
APOA1, IGF1, KLK1, SPP1
 Reactome 4 / 125 20.2× 3.84e-5 1.08e-3 ✓ sig.
Adrenergic signaling in cardiomyocytes
ATP2A2, AGT, AGTR2, RYR2
 KEGG 4 / 154 16.4× 8.67e-5 2.07e-3 ✓ sig.
Synthesis, secretion, and deacylation of Ghrelin
IGF1, INS
 Reactome 2 / 19 66.5× 3.99e-4 6.94e-3 ✓ sig.
Insulin resistance
AGT, INS, TNF
 KEGG 3 / 109 17.4× 6.34e-4 9.94e-3 ✓ sig.
PPARA activates gene expression
AGT, APOA1, NCOR1
 Reactome 3 / 115 16.5× 7.41e-4 1.12e-2 ✓ sig.
AMPK signaling pathway
IGF1, INS, LEPR
 KEGG 3 / 122 15.5× 8.80e-4 1.27e-2 ✓ sig.
African trypanosomiasis
APOA1, TNF
 KEGG 2 / 37 34.2× 1.53e-3 1.94e-2 ✓ sig.
Aldosterone-regulated sodium reabsorption
IGF1, INS
 KEGG 2 / 38 33.3× 1.61e-3 2.02e-2 ✓ sig.
Non-alcoholic fatty liver disease
INS, LEPR, TNF
 KEGG 3 / 157 12.1× 1.82e-3 2.22e-2 ✓ sig.
mTOR signaling pathway
IGF1, INS, TNF
 KEGG 3 / 158 12.0× 1.85e-3 2.24e-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 ⇵
nitric oxide-cGMP-mediated signaling
AGT, AGTR2, INS
 GO:0038060 3 / 10 295× 1.06e-7 1.30e-5 ✓ sig.
G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger
AGT, AGTR2
 GO:0007199 2 / 2 984× 9.79e-7 8.30e-5 ✓ sig.
positive regulation of mitotic nuclear division
IGF1, INS, TNF
 GO:0045840 3 / 29 102× 3.20e-6 2.17e-4 ✓ sig.
negative regulation of neurotrophin TRK receptor signaling pathway
AGT, AGTR2
 GO:0051387 2 / 4 492× 5.87e-6 3.53e-4 ✓ sig.
response to macrophage colony-stimulating factor
SPP1, TNF
 GO:0036005 2 / 4 492× 5.87e-6 3.53e-4 ✓ sig.
positive regulation of extrinsic apoptotic signaling pathway
AGT, AGTR2, TNF
 GO:2001238 3 / 38 77.6× 7.35e-6 4.23e-4 ✓ sig.
sarcoplasmic reticulum calcium ion transport
ATP2A2, RYR2
 GO:0070296 2 / 5 393× 9.78e-6 5.30e-4 ✓ sig.
blood vessel remodeling
AGT, AGTR2, IGF1
 GO:0001974 3 / 42 70.3× 9.98e-6 5.39e-4 ✓ sig.
vasodilation
AGTR2, INS, TNF
 GO:0042311 3 / 50 59.0× 1.69e-5 8.15e-4 ✓ sig.
cellular response to amyloid-beta
APOA1, IGF1, TNF
 GO:1904646 3 / 53 55.7× 2.02e-5 9.36e-4 ✓ sig.
positive regulation of cholesterol metabolic process
AGT, APOA1
 GO:0090205 2 / 7 281× 2.05e-5 9.47e-4 ✓ sig.
negative regulation of cytokine production involved in immune response
APOA1, TNF
 GO:0002719 2 / 7 281× 2.05e-5 9.47e-4 ✓ sig.
negative regulation of fatty acid metabolic process
INS, NCOR1
 GO:0045922 2 / 11 179× 5.36e-5 1.96e-3 ✓ sig.
regulation of protein secretion
INS, TNF
 GO:0050708 2 / 11 179× 5.36e-5 1.96e-3 ✓ sig.
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
AGT, IGF1, INS, TNF
 GO:0051897 4 / 217 18.1× 5.98e-5 2.12e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Diabetic cardiomyopathy Rhabdomyolysis 0.150 3 3.34e-8 2.52e-7 ✓ sig.
Asymptomatic hyperckemia-myalgia-rhabdomyolysis syndrome Distal anoctaminopathy 0.500 1 6.49e-5 2.33e-4 ✓ sig.
Asymptomatic hyperckemia-myalgia-rhabdomyolysis syndrome gnathodiaphyseal dysplasia 0.500 1 6.49e-5 2.33e-4 ✓ sig.
Distal anoctaminopathy gnathodiaphyseal dysplasia 0.500 1 6.49e-5 2.33e-4 ✓ sig.
Acrokeratosis verruciformis Rhabdomyolysis 0.111 1 5.20e-4 1.06e-3 ✓ sig.
Asymptomatic hyperckemia-myalgia-rhabdomyolysis syndrome Rhabdomyolysis 0.111 1 5.20e-4 1.06e-3 ✓ sig.
Distal anoctaminopathy Rhabdomyolysis 0.111 1 5.20e-4 1.06e-3 ✓ sig.
gnathodiaphyseal dysplasia Rhabdomyolysis 0.111 1 5.20e-4 1.06e-3 ✓ sig.
Acrokeratosis verruciformis Diabetic cardiomyopathy 0.067 1 9.09e-4 1.58e-3 ✓ sig.