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 288

6 diseases · 9 shared-gene connections
6 Diseases
29 Unique genes
0.145 Avg. similarity score
Exudative retinopathy Most-connected disease (5 links)
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Disease Searched: Exudative vitreoretinopathy 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 ⇵
Exudative retinopathy 5 5 7
Exudative vitreoretinopathy 4 4 9
FZD4-related exudative vitreoretinopathy 3 3 1
Retinopathy of prematurity 3 3 20
RCBTB1-related retinopathy 2 2 1
Diencephalic mesencephalic junction dysplasia 1 1 3

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

Gene ⇵ Member diseases ⇵ Linked diseases
FZD4 4 / 6 Exudative retinopathy, Exudative vitreoretinopathy, FZD4-related exudative vitreoretinopathy, Retinopathy of prematurity
NDP 3 / 6 Exudative retinopathy, Exudative vitreoretinopathy, Retinopathy of prematurity
PRSS23 3 / 6 Exudative retinopathy, Exudative vitreoretinopathy, Retinopathy of prematurity
RCBTB1 3 / 6 Exudative retinopathy, Exudative vitreoretinopathy, RCBTB1-related retinopathy
LRP5 2 / 6 Exudative vitreoretinopathy, Retinopathy of prematurity
PCDH12 2 / 6 Diencephalic mesencephalic junction dysplasia, Exudative retinopathy
RNF14 2 / 6 Diencephalic mesencephalic junction dysplasia, Exudative retinopathy
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 ⇵
RNF mutants show enhanced WNT signaling and proliferation
FZD4, LRP5, LRP6
 Reactome 3 / 8 155× 7.03e-7 3.83e-5 ✓ sig.
Regulation of FZD by ubiquitination
FZD4, LRP5, LRP6
 Reactome 3 / 21 59.2× 1.64e-5 5.33e-4 ✓ sig.
Cell adhesion molecules
CLDN12, CLDN14, HLA-B, HLA-DRB1, PTPRD
 KEGG 5 / 160 12.9× 3.61e-5 1.02e-3 ✓ sig.
Disassembly of the destruction complex and recruitment of AXIN to the membrane
CTNNB1, LRP5, LRP6
 Reactome 3 / 30 41.4× 4.92e-5 1.32e-3 ✓ sig.
Negative regulation of TCF-dependent signaling by WNT ligand antagonists
LRP5, LRP6
 Reactome 2 / 8 104× 1.56e-4 3.30e-3 ✓ sig.
Breast cancer
FZD4, CTNNB1, LRP5, LRP6
 KEGG 4 / 148 11.2× 4.14e-4 7.15e-3 ✓ sig.
Gastric cancer
FZD4, CTNNB1, LRP5, LRP6
 KEGG 4 / 150 11.0× 4.35e-4 7.44e-3 ✓ sig.
Basal cell carcinoma
FZD4, CTNNB1, GLI3
 KEGG 3 / 63 19.7× 4.56e-4 7.72e-3 ✓ sig.
Hepatocellular carcinoma
FZD4, CTNNB1, LRP5, LRP6
 KEGG 4 / 170 9.7× 6.98e-4 1.07e-2 ✓ sig.
Wnt signaling pathway
FZD4, CTNNB1, LRP5, LRP6
 KEGG 4 / 174 9.5× 7.62e-4 1.14e-2 ✓ sig.
Pathways in cancer
FZD4, CTNNB1, LRP5, LRP6, AGT, GLI3
 KEGG 6 / 533 4.7× 1.47e-3 1.89e-2 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
AGT, NOS3, SERPINE1
 KEGG 3 / 101 12.3× 1.80e-3 2.20e-2 ✓ sig.
VEGFR2 mediated vascular permeability
CTNNB1, NOS3
 Reactome 2 / 29 28.6× 2.20e-3 2.54e-2 ✓ sig.
Leukocyte transendothelial migration
CTNNB1, CLDN12, CLDN14
 KEGG 3 / 116 10.7× 2.67e-3 2.91e-2 ✓ sig.
Allograft rejection
HLA-B, HLA-DRB1
 KEGG 2 / 39 21.2× 3.95e-3 3.85e-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 ⇵
Norrin signaling pathway
FZD4, NDP, LRP5, TSPAN12
 GO:0110135 4 / 4 644× 4.68e-12 1.88e-9 ✓ sig.
establishment of blood-brain barrier
FZD4, NDP, CTNNB1, LRP5
 GO:0060856 4 / 11 234× 1.53e-9 3.30e-7 ✓ sig.
extracellular matrix-cell signaling
FZD4, NDP, LRP5
 GO:0035426 3 / 4 483× 1.34e-8 2.20e-6 ✓ sig.
retinal blood vessel morphogenesis
FZD4, NDP, LRP5
 GO:0061304 3 / 6 322× 6.70e-8 8.74e-6 ✓ sig.
establishment of blood-retinal barrier
NDP, CTNNB1, LRP5
 GO:1990963 3 / 6 322× 6.70e-8 8.74e-6 ✓ sig.
retina vasculature morphogenesis in camera-type eye
FZD4, NDP, LRP5
 GO:0061299 3 / 7 276× 1.17e-7 1.41e-5 ✓ sig.
canonical Wnt signaling pathway
FZD4, NDP, CTNNB1, LRP5, LRP6
 GO:0060070 5 / 105 30.7× 5.43e-7 5.13e-5 ✓ sig.
Wnt signaling pathway
FZD4, NDP, CTNNB1, LRP5, LRP6, CDK14
 GO:0016055 6 / 232 16.7× 1.28e-6 1.04e-4 ✓ sig.
retina vasculature development in camera-type eye
FZD4, NDP, LRP5
 GO:0061298 3 / 15 129× 1.51e-6 1.19e-4 ✓ sig.
positive regulation of DNA-templated transcription
RNF14, FZD4, NDP, CTNNB1, LRP5, LRP6, AGT, GLI3, HLA-DRB1
 GO:0045893 9 / 778 7.5× 1.70e-6 1.31e-4 ✓ sig.
embryonic digit morphogenesis
CTNNB1, LRP5, GLI3, IHH
 GO:0042733 4 / 57 45.2× 1.75e-6 1.34e-4 ✓ sig.
gene expression
NDP, RHO, CTNNB1, LRP5, GLI3, SOD1
 GO:0010467 6 / 269 14.4× 3.03e-6 2.07e-4 ✓ sig.
negative regulation of chondrocyte differentiation
CTNNB1, GLI3, IHH
 GO:0032331 3 / 23 84.0× 5.83e-6 3.51e-4 ✓ sig.
negative regulation of alpha-beta T cell differentiation
GLI3, IHH
 GO:0046639 2 / 3 430× 6.97e-6 4.05e-4 ✓ sig.
regulation of blood pressure
LRP5, AGT, NOS3, SOD1
 GO:0008217 4 / 83 31.1× 7.90e-6 4.49e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Exudative retinopathy Exudative vitreoretinopathy 0.308 4 1.88e-12 2.18e-11 ✓ sig.
Exudative vitreoretinopathy Retinopathy of prematurity 0.154 4 2.60e-10 2.48e-9 ✓ sig.
Exudative retinopathy Retinopathy of prematurity 0.120 3 6.54e-8 4.74e-7 ✓ sig.
Diencephalic mesencephalic junction dysplasia Exudative retinopathy 0.222 2 5.31e-7 3.27e-6 ✓ sig.
Exudative retinopathy FZD4-related exudative vitreoretinopathy 0.125 1 4.55e-4 9.73e-4 ✓ sig.
Exudative retinopathy RCBTB1-related retinopathy 0.125 1 4.55e-4 9.73e-4 ✓ sig.
Exudative vitreoretinopathy FZD4-related exudative vitreoretinopathy 0.100 1 5.84e-4 1.16e-3 ✓ sig.
Exudative vitreoretinopathy RCBTB1-related retinopathy 0.100 1 5.84e-4 1.16e-3 ✓ sig.
FZD4-related exudative vitreoretinopathy Retinopathy of prematurity 0.048 1 1.30e-3 2.06e-3 ✓ sig.