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 81

12 diseases · 24 shared-gene connections
12 Diseases
34 Unique genes
0.303 Avg. similarity score
Mitral valve disease Most-connected disease (8 links)
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Disease Searched: krabbe disease 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 ⇵
Mitral valve disease 8 8 2
Rheumatic disease of mitral valve 6 6 2
Rheumatic mitral regurgitation 6 6 2
Microvascular angina 5 5 1
homocystinuria due to methylene tetrahydrofolate reductase deficiency 5 5 1
Coronary restenosis 4 4 14
Portal vein thrombosis 4 4 3
renal tubular dysgenesis - ACE 4 4 1
Fabry disease 3 3 9
Carotid artery stenosis 1 1 13
Congenital plasminogen activator inhibitor deficiency type 1 1 1 1
krabbe disease 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
MTHFR 8 / 12 Carotid artery stenosis, Coronary restenosis, homocystinuria due to methylene tetrahydrofolate reductase deficiency, Microvascular angina and 4 more
ACE 6 / 12 Coronary restenosis, Fabry disease, Mitral valve disease, renal tubular dysgenesis - ACE and 2 more
GALC 2 / 12 Fabry disease, krabbe disease
MMP3 2 / 12 Carotid artery stenosis, Coronary restenosis
SERPINE1 2 / 12 Congenital plasminogen activator inhibitor deficiency type 1, Portal vein thrombosis
SPP1 2 / 12 Carotid artery stenosis, Coronary restenosis
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 ⇵
Interleukin-4 and Interleukin-13 signaling
MMP1, MMP3, HMOX1, ITGB2, TNF, TP53, IL1A
 Reactome 7 / 108 22.9× 1.72e-8 1.37e-6 ✓ sig.
Coronavirus disease - COVID-19
F2, MMP1, MMP3, ACE, MBL2, TNF, RPL36A-HNRNPH2
 KEGG 7 / 238 10.4× 3.75e-6 1.52e-4 ✓ sig.
Rheumatoid arthritis
MMP1, MMP3, ITGB2, TNF, IL1A
 KEGG 5 / 95 18.6× 6.46e-6 2.38e-4 ✓ sig.
Complement and coagulation cascades
F2, SERPINE1, ITGB2, MBL2
 KEGG 4 / 88 16.1× 1.06e-4 2.37e-3 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
SERPINE1, TNF, AGT, IL1A
 KEGG 4 / 101 14.0× 1.80e-4 3.63e-3 ✓ sig.
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
APOE, F2, MMP1, SPP1
 Reactome 4 / 125 11.3× 4.07e-4 6.94e-3 ✓ sig.
Fluid shear stress and atherosclerosis
HMOX1, TNF, TP53, IL1A
 KEGG 4 / 141 10.0× 6.42e-4 9.89e-3 ✓ sig.
Mineral absorption
MT2A, HMOX1, VDR
 KEGG 3 / 61 17.4× 6.67e-4 1.02e-2 ✓ sig.
Degradation of the extracellular matrix
MMP1, MMP3, SPP1
 Reactome 3 / 70 15.1× 9.97e-4 1.39e-2 ✓ sig.
Metabolism of Angiotensinogen to Angiotensins
ACE, AGT
 Reactome 2 / 17 41.6× 1.03e-3 1.42e-2 ✓ sig.
PPAR signaling pathway
FABP2, MMP1, ADIPOQ
 KEGG 3 / 76 13.9× 1.27e-3 1.66e-2 ✓ sig.
Pertussis
ITGB2, TNF, IL1A
 KEGG 3 / 78 13.6× 1.36e-3 1.76e-2 ✓ sig.
Leishmaniasis
ITGB2, TNF, IL1A
 KEGG 3 / 78 13.6× 1.36e-3 1.76e-2 ✓ sig.
Tuberculosis
ITGB2, TNF, IL1A, VDR
 KEGG 4 / 181 7.8× 1.63e-3 2.01e-2 ✓ sig.
Renin-angiotensin system
ACE, AGT
 KEGG 2 / 23 30.7× 1.90e-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 ⇵
response to glucocorticoid
ADIPOQ, BCHE, TNF, UCP3
 GO:0051384 4 / 53 41.5× 2.51e-6 1.77e-4 ✓ sig.
negative regulation of blood coagulation
APOE, F2, SERPINE1
 GO:0030195 3 / 16 103× 3.03e-6 2.05e-4 ✓ sig.
regulation of renal output by angiotensin
ACE, AGT
 GO:0002019 2 / 2 550× 3.21e-6 2.15e-4 ✓ sig.
positive regulation of angiogenesis
PTGIS, SERPINE1, HMOX1, ITGB2, IL1A
 GO:0045766 5 / 159 17.3× 9.54e-6 5.13e-4 ✓ sig.
decidualization
PTGIS, SPP1, VDR
 GO:0046697 3 / 25 66.0× 1.23e-5 6.21e-4 ✓ sig.
negative regulation of proteolysis
F2, SERPINE1, TP53
 GO:0045861 3 / 27 61.1× 1.56e-5 7.51e-4 ✓ sig.
response to macrophage colony-stimulating factor
SPP1, TNF
 GO:0036005 2 / 4 275× 1.92e-5 8.84e-4 ✓ sig.
positive regulation of protein-containing complex disassembly
TNF, IGF1R
 GO:0043243 2 / 4 275× 1.92e-5 8.84e-4 ✓ sig.
cellular response to lipopolysaccharide
CXCL9, MMP3, SERPINE1, TNF, IL1A
 GO:0071222 5 / 187 14.7× 2.09e-5 9.44e-4 ✓ sig.
positive regulation of reactive oxygen species metabolic process
F2, TP53, AGT
 GO:2000379 3 / 34 48.5× 3.17e-5 1.29e-3 ✓ sig.
maintenance of blood vessel diameter homeostasis by renin-angiotensin
ACE, AGT
 GO:0002034 2 / 5 220× 3.20e-5 1.30e-3 ✓ sig.
cellular extravasation
ITGB2, TNF
 GO:0045123 2 / 5 220× 3.20e-5 1.30e-3 ✓ sig.
regulation of systemic arterial blood pressure by renin-angiotensin
ACE, AGT
 GO:0003081 2 / 6 183× 4.80e-5 1.77e-3 ✓ sig.
positive regulation of nitric oxide biosynthetic process
APOE, ITGB2, TNF
 GO:0045429 3 / 42 39.3× 6.02e-5 2.10e-3 ✓ sig.
positive regulation of cholesterol metabolic process
APOE, AGT
 GO:0090205 2 / 7 157× 6.71e-5 2.29e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Rheumatic disease of mitral valve Rheumatic mitral regurgitation 0.667 2 8.44e-9 6.84e-8 ✓ sig.
Mitral valve disease Rheumatic mitral regurgitation 0.667 2 8.44e-9 6.84e-8 ✓ sig.
Mitral valve disease Rheumatic disease of mitral valve 0.667 2 8.44e-9 6.84e-8 ✓ sig.
Carotid artery stenosis Coronary restenosis 0.120 3 1.70e-7 1.15e-6 ✓ sig.
Coronary restenosis Mitral valve disease 0.133 2 7.68e-7 4.59e-6 ✓ sig.
Coronary restenosis Rheumatic disease of mitral valve 0.133 2 7.68e-7 4.59e-6 ✓ sig.
Coronary restenosis Rheumatic mitral regurgitation 0.133 2 7.68e-7 4.59e-6 ✓ sig.
homocystinuria due to methylene tetrahydrofolate reductase deficiency Microvascular angina 0.500 1 6.49e-5 2.32e-4 ✓ sig.
Microvascular angina Mitral valve disease 0.333 1 1.30e-4 3.91e-4 ✓ sig.
renal tubular dysgenesis - ACE Rheumatic mitral regurgitation 0.333 1 1.30e-4 3.91e-4 ✓ sig.
renal tubular dysgenesis - ACE Rheumatic disease of mitral valve 0.333 1 1.30e-4 3.91e-4 ✓ sig.
Mitral valve disease renal tubular dysgenesis - ACE 0.333 1 1.30e-4 3.91e-4 ✓ sig.
Microvascular angina Rheumatic mitral regurgitation 0.333 1 1.30e-4 3.91e-4 ✓ sig.
Microvascular angina Rheumatic disease of mitral valve 0.333 1 1.30e-4 3.91e-4 ✓ sig.
homocystinuria due to methylene tetrahydrofolate reductase deficiency Rheumatic mitral regurgitation 0.333 1 1.30e-4 3.91e-4 ✓ sig.
homocystinuria due to methylene tetrahydrofolate reductase deficiency Rheumatic disease of mitral valve 0.333 1 1.30e-4 3.91e-4 ✓ sig.
homocystinuria due to methylene tetrahydrofolate reductase deficiency Mitral valve disease 0.333 1 1.30e-4 3.91e-4 ✓ sig.
Microvascular angina Portal vein thrombosis 0.250 1 1.95e-4 5.32e-4 ✓ sig.
homocystinuria due to methylene tetrahydrofolate reductase deficiency Portal vein thrombosis 0.250 1 1.95e-4 5.32e-4 ✓ sig.
Congenital plasminogen activator inhibitor deficiency type 1 Portal vein thrombosis 0.250 1 1.95e-4 5.32e-4 ✓ sig.
Mitral valve disease Portal vein thrombosis 0.200 1 3.90e-4 8.64e-4 ✓ sig.
Fabry disease krabbe disease 0.100 1 5.84e-4 1.15e-3 ✓ sig.
Fabry disease renal tubular dysgenesis - ACE 0.100 1 5.84e-4 1.15e-3 ✓ sig.
Fabry disease Mitral valve disease 0.091 1 1.17e-3 1.89e-3 ✓ sig.