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 60

15 diseases · 35 shared-gene connections
15 Diseases
40 Unique genes
0.302 Avg. similarity score
Mitral valve disease Most-connected disease (9 links)
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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 9 9 2
Cervical dysplasia 7 7 2
Microvascular angina 7 7 1
homocystinuria due to methylene tetrahydrofolate reductase deficiency 7 7 1
Rheumatic disease of mitral valve 6 6 2
Rheumatic mitral regurgitation 6 6 2
Uterine disease 6 6 2
Coronary restenosis 4 4 14
renal tubular dysgenesis - ACE 4 4 1
Ataxia with intention tremor and hypotonia 3 3 1
Cerebellar dysfunction with variable cognitive and behavioral abnormalities 3 3 6
Fabry disease 3 3 9
Portal vein thrombosis 3 3 3
Carotid artery stenosis 1 1 13
krabbe disease 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
MTHFR 10 / 15 Carotid artery stenosis, Cervical dysplasia, Coronary restenosis, homocystinuria due to methylene tetrahydrofolate reductase deficiency and 6 more
ACE 6 / 15 Coronary restenosis, Fabry disease, Mitral valve disease, renal tubular dysgenesis - ACE and 2 more
POU4F1 4 / 15 Ataxia with intention tremor and hypotonia, Cerebellar dysfunction with variable cognitive and behavioral abnormalities, Cervical dysplasia, Uterine disease
GALC 2 / 15 Fabry disease, krabbe disease
MMP3 2 / 15 Carotid artery stenosis, Coronary restenosis
SPP1 2 / 15 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 19.5× 5.71e-8 4.01e-6 ✓ sig.
Coronavirus disease - COVID-19
F2, MMP1, MMP3, ACE, MBL2, TNF, RPL36A-HNRNPH2
 KEGG 7 / 238 8.8× 1.17e-5 3.83e-4 ✓ sig.
Rheumatoid arthritis
MMP1, MMP3, ITGB2, TNF, IL1A
 KEGG 5 / 95 15.8× 1.47e-5 4.63e-4 ✓ sig.
Degradation of the extracellular matrix
MMP1, MMP3, SPP1, NID1
 Reactome 4 / 70 17.2× 8.25e-5 1.92e-3 ✓ sig.
Complement and coagulation cascades
F2, ITGB2, MBL2, SERPINE1
 KEGG 4 / 88 13.6× 2.01e-4 3.92e-3 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
TNF, AGT, IL1A, SERPINE1
 KEGG 4 / 101 11.9× 3.41e-4 5.93e-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 9.6× 7.65e-4 1.11e-2 ✓ sig.
Regulation of TP53 Activity through Association with Co-factors
POU4F1, TP53
 Reactome 2 / 14 42.9× 9.60e-4 1.32e-2 ✓ sig.
Mineral absorption
MT2A, HMOX1, VDR
 KEGG 3 / 61 14.8× 1.08e-3 1.44e-2 ✓ sig.
Apelin signaling pathway
SPP1, SLC9A1, MYLK2, SERPINE1
 KEGG 4 / 140 8.6× 1.17e-3 1.52e-2 ✓ sig.
Fluid shear stress and atherosclerosis
HMOX1, TNF, TP53, IL1A
 KEGG 4 / 141 8.5× 1.20e-3 1.55e-2 ✓ sig.
Metabolism of Angiotensinogen to Angiotensins
ACE, AGT
 Reactome 2 / 17 35.3× 1.43e-3 1.77e-2 ✓ sig.
PPAR signaling pathway
FABP2, MMP1, ADIPOQ
 KEGG 3 / 76 11.9× 2.03e-3 2.31e-2 ✓ sig.
Pertussis
ITGB2, TNF, IL1A
 KEGG 3 / 78 11.5× 2.19e-3 2.44e-2 ✓ sig.
Leishmaniasis
ITGB2, TNF, IL1A
 KEGG 3 / 78 11.5× 2.19e-3 2.44e-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 ⇵
regulation of renal output by angiotensin
ACE, AGT
 GO:0002019 2 / 2 467× 4.47e-6 2.74e-4 ✓ sig.
response to glucocorticoid
ADIPOQ, BCHE, TNF, UCP3
 GO:0051384 4 / 53 35.3× 4.89e-6 2.95e-4 ✓ sig.
negative regulation of blood coagulation
APOE, F2, SERPINE1
 GO:0030195 3 / 16 87.6× 4.99e-6 3.00e-4 ✓ sig.
positive regulation of calcineurin-NFAT signaling cascade
CAMTA1, SLC9A1, TNF
 GO:0070886 3 / 21 66.7× 1.18e-5 5.92e-4 ✓ sig.
positive regulation of mitochondrial membrane permeability
SLC9A1, TP53
 GO:0035794 2 / 3 311× 1.34e-5 6.55e-4 ✓ sig.
extracellular matrix organization
MMP1, MMP3, TNFRSF11B, NID1, TNF
 GO:0030198 5 / 145 16.1× 1.39e-5 6.74e-4 ✓ sig.
decidualization
PTGIS, SPP1, VDR
 GO:0046697 3 / 25 56.1× 2.02e-5 9.06e-4 ✓ sig.
positive regulation of angiogenesis
PTGIS, HMOX1, ITGB2, IL1A, SERPINE1
 GO:0045766 5 / 159 14.7× 2.17e-5 9.56e-4 ✓ sig.
negative regulation of proteolysis
F2, TP53, SERPINE1
 GO:0045861 3 / 27 51.9× 2.56e-5 1.08e-3 ✓ sig.
response to macrophage colony-stimulating factor
SPP1, TNF
 GO:0036005 2 / 4 234× 2.67e-5 1.12e-3 ✓ sig.
positive regulation of protein-containing complex disassembly
TNF, IGF1R
 GO:0043243 2 / 4 234× 2.67e-5 1.12e-3 ✓ sig.
maintenance of blood vessel diameter homeostasis by renin-angiotensin
ACE, AGT
 GO:0002034 2 / 5 187× 4.45e-5 1.65e-3 ✓ sig.
cellular extravasation
ITGB2, TNF
 GO:0045123 2 / 5 187× 4.45e-5 1.65e-3 ✓ sig.
cellular response to lipopolysaccharide
CXCL9, MMP3, TNF, IL1A, SERPINE1
 GO:0071222 5 / 187 12.5× 4.71e-5 1.72e-3 ✓ sig.
positive regulation of reactive oxygen species metabolic process
F2, TP53, AGT
 GO:2000379 3 / 34 41.2× 5.19e-5 1.85e-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 7.20e-8 ✓ sig.
Cervical dysplasia Uterine disease 0.667 2 8.44e-9 7.20e-8 ✓ sig.
Mitral valve disease Rheumatic mitral regurgitation 0.667 2 8.44e-9 7.20e-8 ✓ sig.
Mitral valve disease Rheumatic disease of mitral valve 0.667 2 8.44e-9 7.20e-8 ✓ sig.
Carotid artery stenosis Coronary restenosis 0.120 3 1.70e-7 1.21e-6 ✓ sig.
Coronary restenosis Mitral valve disease 0.133 2 7.68e-7 4.83e-6 ✓ sig.
Coronary restenosis Rheumatic disease of mitral valve 0.133 2 7.68e-7 4.83e-6 ✓ sig.
Coronary restenosis Rheumatic mitral regurgitation 0.133 2 7.68e-7 4.83e-6 ✓ sig.
homocystinuria due to methylene tetrahydrofolate reductase deficiency Microvascular angina 0.500 1 6.49e-5 2.34e-4 ✓ sig.
homocystinuria due to methylene tetrahydrofolate reductase deficiency Rheumatic mitral regurgitation 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Ataxia with intention tremor and hypotonia Uterine disease 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Microvascular angina Mitral valve disease 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Microvascular angina Rheumatic disease of mitral valve 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Microvascular angina Rheumatic mitral regurgitation 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Mitral valve disease renal tubular dysgenesis - ACE 0.333 1 1.30e-4 3.90e-4 ✓ sig.
renal tubular dysgenesis - ACE Rheumatic disease of mitral valve 0.333 1 1.30e-4 3.90e-4 ✓ sig.
renal tubular dysgenesis - ACE Rheumatic mitral regurgitation 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Microvascular angina Uterine disease 0.333 1 1.30e-4 3.90e-4 ✓ sig.
homocystinuria due to methylene tetrahydrofolate reductase deficiency Uterine disease 0.333 1 1.30e-4 3.90e-4 ✓ sig.
homocystinuria due to methylene tetrahydrofolate reductase deficiency Rheumatic disease of mitral valve 0.333 1 1.30e-4 3.90e-4 ✓ sig.
homocystinuria due to methylene tetrahydrofolate reductase deficiency Mitral valve disease 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Cervical dysplasia homocystinuria due to methylene tetrahydrofolate reductase deficiency 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Cervical dysplasia Microvascular angina 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Ataxia with intention tremor and hypotonia Cervical dysplasia 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Microvascular angina Portal vein thrombosis 0.250 1 1.95e-4 5.28e-4 ✓ sig.
homocystinuria due to methylene tetrahydrofolate reductase deficiency Portal vein thrombosis 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Cervical dysplasia Mitral valve disease 0.250 1 2.60e-4 6.40e-4 ✓ sig.
Mitral valve disease Uterine disease 0.250 1 2.60e-4 6.40e-4 ✓ sig.
Cervical dysplasia Portal vein thrombosis 0.200 1 3.90e-4 8.52e-4 ✓ sig.
Ataxia with intention tremor and hypotonia Cerebellar dysfunction with variable cognitive and behavioral abnormalities 0.143 1 3.90e-4 8.52e-4 ✓ sig.
Fabry disease krabbe disease 0.100 1 5.84e-4 1.14e-3 ✓ sig.
Fabry disease renal tubular dysgenesis - ACE 0.100 1 5.84e-4 1.14e-3 ✓ sig.
Cerebellar dysfunction with variable cognitive and behavioral abnormalities Uterine disease 0.125 1 7.79e-4 1.39e-3 ✓ sig.
Cerebellar dysfunction with variable cognitive and behavioral abnormalities Cervical dysplasia 0.125 1 7.79e-4 1.39e-3 ✓ sig.
Fabry disease Mitral valve disease 0.091 1 1.17e-3 1.88e-3 ✓ sig.