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 372

5 diseases · 6 shared-gene connections
5 Diseases
127 Unique genes
0.073 Avg. similarity score
Ventricular remodeling Most-connected disease (4 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 ⇵
Ventricular remodeling 4 4 25
Cardiomegaly 3 3 84
HAND2 related congenital heart defect 2 2 1
Ventricular dysfunction 2 2 46
oligodontia-cancer predisposition syndrome 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
AGT 3 / 5 Cardiomegaly, Ventricular dysfunction, Ventricular remodeling
AKT1 3 / 5 Cardiomegaly, Ventricular dysfunction, Ventricular remodeling
HAND2 3 / 5 Cardiomegaly, HAND2 related congenital heart defect, Ventricular remodeling
MYH6 3 / 5 Cardiomegaly, Ventricular dysfunction, Ventricular remodeling
NPPB 3 / 5 Cardiomegaly, Ventricular dysfunction, Ventricular remodeling
SIRT6 3 / 5 Cardiomegaly, Ventricular dysfunction, Ventricular remodeling
ATP2A2 2 / 5 Cardiomegaly, Ventricular dysfunction
AXIN2 2 / 5 oligodontia-cancer predisposition syndrome, Ventricular remodeling
CTNNB1 2 / 5 Ventricular dysfunction, Ventricular remodeling
DMD 2 / 5 Cardiomegaly, Ventricular dysfunction
FNDC5 2 / 5 Cardiomegaly, Ventricular dysfunction
GATA4 2 / 5 Cardiomegaly, Ventricular remodeling
IDH2 2 / 5 Cardiomegaly, Ventricular dysfunction
LEP 2 / 5 Cardiomegaly, Ventricular remodeling
MFN2 2 / 5 Cardiomegaly, Ventricular remodeling
NFE2L2 2 / 5 Ventricular dysfunction, Ventricular remodeling
NPPA 2 / 5 Cardiomegaly, Ventricular remodeling
PLPP3 2 / 5 Cardiomegaly, Ventricular dysfunction
PRKAA2 2 / 5 Cardiomegaly, Ventricular dysfunction
ROCK2 2 / 5 Cardiomegaly, Ventricular remodeling
SOD2 2 / 5 Cardiomegaly, Ventricular dysfunction
TBX20 2 / 5 Cardiomegaly, Ventricular remodeling
TNF 2 / 5 Cardiomegaly, Ventricular dysfunction
TNNT2 2 / 5 Cardiomegaly, Ventricular dysfunction
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 ⇵
cGMP-PKG signaling pathway
ADRA1B, ADRA2A, ADRA2C, AKT1, ATP2A2, GATA4, ITPR2, MYH6, NOS3, NPPA, NPPB, NPR1
 KEGG 23 / 166 13.1× 1.20e-19 8.93e-17 ✓ sig.
Proteoglycans in cancer
AKT1, CAV1, CAV3, FGF2, HIF1A, IGF1, ITPR2, PRKCA, PRKCB, ROCK2, SRC, STAT3
 KEGG 21 / 204 9.7× 2.57e-15 9.14e-13 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
AGT, AKT1, EDN1, IL1B, NOS3, PRKCA, PRKCB, PRKCZ, STAT3, TNF, IL6, PIK3CA
 KEGG 16 / 101 15.0× 6.99e-15 2.29e-12 ✓ sig.
Pathways in cancer
AGT, AKT1, CCND2, EDN1, FGF2, GSK3B, HDAC2, HIF1A, HMOX1, IGF1, PLD1, PLD2
 KEGG 30 / 533 5.3× 2.47e-14 7.02e-12 ✓ sig.
Diabetic cardiomyopathy
AGT, AKT1, ATP2A2, CPT1B, GSK3B, NOS3, PPARA, PRKCA, PRKCB, PRKCZ, REN, SLC2A4
 KEGG 20 / 205 9.2× 3.55e-14 9.84e-12 ✓ sig.
Hormone signaling
ADRA1B, ADRA2A, ADRA2C, AGT, IGF1, LEP, NPPA, NPPB, NPR1, POMC, SRC, STAT3
 KEGG 20 / 219 8.6× 1.25e-13 3.12e-11 ✓ sig.
cAMP signaling pathway
AKT1, ATP2A2, EDN1, NPPA, NPR1, PLD1, PLD2, POMC, PPARA, ROCK2, ADORA1, ADORA2A
 KEGG 20 / 226 8.4× 2.28e-13 5.44e-11 ✓ sig.
Insulin resistance
AGT, AKT1, CPT1B, GSK3B, NOS3, PPARA, PRKAA2, PRKCB, PRKCZ, SLC2A4, STAT3, TNF
 KEGG 15 / 109 13.0× 4.38e-13 1.00e-10 ✓ sig.
Fluid shear stress and atherosclerosis
AKT1, CAV1, CAV3, EDN1, HMOX1, IL1B, NOS3, PRKAA2, PRKCZ, SRC, TNF, CTNNB1
 KEGG 16 / 141 10.7× 1.48e-12 3.16e-10 ✓ sig.
Hypertrophic cardiomyopathy
AGT, ATP2A2, CAV3, DMD, EDN1, IGF1, MYBPC3, MYH6, PRKAA2, TNF, TNNT2, IL6
 KEGG 14 / 99 13.4× 1.88e-12 3.91e-10 ✓ sig.
Thyroid hormone signaling pathway
AKT1, ATP2A2, GATA4, GSK3B, HDAC2, HIF1A, MYH6, PRKCA, PRKCB, SRC, ATP1A3, CTNNB1
 KEGG 15 / 122 11.6× 2.37e-12 4.82e-10 ✓ sig.
Dilated cardiomyopathy
AGT, ATP2A2, CAV3, DMD, IGF1, MYBPC3, MYH6, TNF, TNNT2, ADRB1, ADCY5, PLN
 KEGG 14 / 105 12.6× 4.30e-12 8.24e-10 ✓ sig.
HIF-1 signaling pathway
AKT1, EDN1, HIF1A, HMOX1, IGF1, NOS3, NPPA, PRKCA, PRKCB, STAT3, IL6, INS
 KEGG 14 / 110 12.0× 8.23e-12 1.51e-9 ✓ sig.
Lipid and atherosclerosis
AKT1, CYP1A1, GSK3B, IL18, IL1B, NOS3, PRKCA, ROCK2, SOD2, SRC, STAT3, TNF
 KEGG 18 / 216 7.9× 1.10e-11 1.96e-9 ✓ sig.
Alcoholic liver disease
AKT1, CPT1B, CYP2E1, GSK3B, IL1B, PPARA, PRKAA2, TNF, ALDH2, CTNNB1, FAS, IL6
 KEGG 15 / 144 9.9× 2.70e-11 4.39e-9 ✓ 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 hypoxia
CAV1, CAV3, CYP1A1, EDN1, HIF1A, ITPR2, LEP, LIF, MYOCD, NPPA, PPARA, SOD2
 GO:0001666 21 / 176 17.6× 1.83e-20 3.22e-17 ✓ sig.
positive regulation of gene expression
AKT1, CAV1, CEBPB, FGF2, GAS6, GSK3B, GSN, HAND2, HIF1A, IGF1, IL18, IL1B
 GO:0010628 30 / 504 8.8× 3.77e-20 6.40e-17 ✓ sig.
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
ADRA2A, ADRA2C, AGT, FGF2, GAS6, GSK3B, IGF1, IL18, IL1B, LEP, PIK3CG, PPARD
 GO:0051897 22 / 217 14.9× 7.77e-20 1.23e-16 ✓ sig.
negative regulation of apoptotic process
AKT1, CCND2, FHL2, GAS6, GSK3B, HDAC2, HIF1A, HTR2B, IGF1, LEP, NKX2-5, PPARD
 GO:0043066 28 / 524 7.9× 1.36e-17 1.55e-14 ✓ sig.
positive regulation of MAPK cascade
ADRA1B, ADRA2A, ADRA2C, EDN1, FGF2, IGF1, IL1B, LEP, LIF, ROCK2, SHC1, TNF
 GO:0043410 20 / 224 13.1× 5.20e-17 5.32e-14 ✓ sig.
positive regulation of transcription by RNA polymerase II
AHR, AKT1, CEBPB, EDN1, FGF2, GATA4, GSK3B, HAND2, HDAC2, HIF1A, IGF1, IL18
 GO:0045944 39 / 1,208 4.8× 7.05e-17 6.99e-14 ✓ sig.
positive regulation of cell population proliferation
ADRA2A, APLN, BAMBI, CAV3, CCND2, CTF1, EDN1, FGF2, HDAC2, HTR2B, IGF1, IL1B
 GO:0008284 27 / 532 7.5× 2.03e-16 1.80e-13 ✓ sig.
vasodilation
ADRA2A, NOS3, NPPA, NPPB, PPARD, SOD2, SRC, TNF, ADORA1, ADORA2A, INS, NOS1
 GO:0042311 12 / 50 35.3× 5.57e-16 4.59e-13 ✓ sig.
positive regulation of smooth muscle cell proliferation
AKT1, EDN1, FGF2, HMOX1, IGF1, IL18, PRKCA, TNF, IL6, PIK3CA, TLR4, TGFB1
 GO:0048661 12 / 52 34.0× 9.36e-16 7.30e-13 ✓ sig.
regulation of the force of heart contraction
APLN, ATP2A2, CAV1, GLRX3, GRK2, MYH6, GAA, PLN, SLC9A1
 GO:0002026 9 / 19 69.7× 2.02e-15 1.50e-12 ✓ sig.
positive regulation of epithelial to mesenchymal transition
AGT, BAMBI, HDAC2, IL1B, TBX20, CTNNB1, IL6, AXIN2, SMAD2, SMAD3, TCF7L2, TGFB1
 GO:0010718 12 / 59 29.9× 4.88e-15 3.36e-12 ✓ sig.
glucose homeostasis
ADRA2A, AKT1, CAV3, HIF1A, LEP, POMC, PRKAA2, SIRT6, SLC2A4, SOX4, STAT3, IL6
 GO:0042593 15 / 134 16.5× 1.81e-14 1.13e-11 ✓ sig.
positive regulation of cardiac muscle hypertrophy
AGT, APLN, EDN1, HAND2, IGF1, PRKCA, ROCK2, ADRA1A, SLC9A1
 GO:0010613 9 / 26 50.9× 6.58e-14 3.72e-11 ✓ sig.
negative regulation of gene expression
AGT, AKT1, APLN, EDN1, FGF2, GSK3B, HAND2, HIF1A, IGF1, PRKAA2, ROCK2, STAT3
 GO:0010629 20 / 339 8.7× 1.48e-13 7.90e-11 ✓ sig.
positive regulation of DNA-templated transcription
AGT, AHR, BAMBI, CEBPB, GATA4, HAND2, HDAC2, HIF1A, IGF1, IL1B, MYOCD, NKX2-5
 GO:0045893 28 / 778 5.3× 2.90e-13 1.49e-10 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Cardiomegaly Ventricular dysfunction 0.120 14 1.38e-21 2.99e-20 ✓ sig.
Cardiomegaly Ventricular remodeling 0.122 12 1.50e-21 3.23e-20 ✓ sig.
Ventricular dysfunction Ventricular remodeling 0.108 7 6.08e-13 7.90e-12 ✓ sig.
HAND2 related congenital heart defect Ventricular remodeling 0.038 1 1.62e-3 2.44e-3 ✓ sig.
oligodontia-cancer predisposition syndrome Ventricular remodeling 0.038 1 1.62e-3 2.44e-3 ✓ sig.
Cardiomegaly HAND2 related congenital heart defect 0.012 1 5.46e-3 6.63e-3 ✓ sig.