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 256

8 diseases · 20 shared-gene connections
8 Diseases
31 Unique genes
0.228 Avg. similarity score
Exudative retinopathy Most-connected disease (7 links)
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Disease Searched: Exudative vitreoretinopathy 2, x-linked 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 7 7 7
Exudative vitreoretinopathy 7 7 12
Coats disease 6 6 2
Atrophia bulborum heritaria 5 5 1
Exudative vitreoretinopathy 2, x-linked 5 5 1
Norrie disease 5 5 1
Retinal dystrophy with or without extraocular anomalies 3 3 1
Retinopathy of prematurity 2 2 20

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

Gene ⇵ Member diseases ⇵ Linked diseases
NDP 7 / 8 Atrophia bulborum heritaria, Coats disease, Exudative retinopathy, Exudative vitreoretinopathy and 3 more
RCBTB1 4 / 8 Coats disease, Exudative retinopathy, Exudative vitreoretinopathy, Retinal dystrophy with or without extraocular anomalies
FZD4 3 / 8 Exudative retinopathy, Exudative vitreoretinopathy, Retinopathy of prematurity
PRSS23 3 / 8 Exudative retinopathy, Exudative vitreoretinopathy, Retinopathy of prematurity
LRP5 2 / 8 Exudative vitreoretinopathy, Retinopathy of prematurity
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 ⇵
VEGFR2 mediated vascular permeability
CTNNB1, NOS3, CTNND1, CTNNA1
 Reactome 4 / 29 53.4× 8.25e-7 3.52e-5 ✓ sig.
RNF mutants show enhanced WNT signaling and proliferation
FZD4, LRP5, LRP6
 Reactome 3 / 8 145× 8.64e-7 3.67e-5 ✓ sig.
Leukocyte transendothelial migration
CTNNB1, CLDN12, CLDN14, CTNND1, CTNNA1
 KEGG 5 / 116 16.7× 1.07e-5 3.08e-4 ✓ sig.
Regulation of FZD by ubiquitination
FZD4, LRP5, LRP6
 Reactome 3 / 21 55.3× 2.01e-5 5.23e-4 ✓ sig.
Breast cancer
FZD4, CTNNB1, LRP5, LRP6, JAG1
 KEGG 5 / 148 13.1× 3.48e-5 8.20e-4 ✓ sig.
Gastric cancer
FZD4, CTNNB1, LRP5, LRP6, CTNNA1
 KEGG 5 / 150 12.9× 3.72e-5 8.63e-4 ✓ sig.
Pathways in cancer
FZD4, CTNNB1, LRP5, LRP6, AGT, GLI3, JAG1, CTNNA1
 KEGG 8 / 533 5.8× 4.55e-5 1.01e-3 ✓ sig.
Cell adhesion molecules
CLDN12, CLDN14, HLA-B, HLA-DRB1, PTPRD
 KEGG 5 / 160 12.1× 5.06e-5 1.10e-3 ✓ sig.
Disassembly of the destruction complex and recruitment of AXIN to the membrane
CTNNB1, LRP5, LRP6
 Reactome 3 / 30 38.7× 6.03e-5 1.27e-3 ✓ sig.
Adherens junctions interactions
CTNNB1, CTNND1, CTNNA1
 Reactome 3 / 32 36.3× 7.34e-5 1.48e-3 ✓ sig.
Negative regulation of TCF-dependent signaling by WNT ligand antagonists
LRP5, LRP6
 Reactome 2 / 8 96.9× 1.79e-4 3.01e-3 ✓ sig.
InlA-mediated entry of Listeria monocytogenes into host cells
CTNNB1, CTNND1
 Reactome 2 / 9 86.1× 2.30e-4 3.66e-3 ✓ sig.
Basal cell carcinoma
FZD4, CTNNB1, GLI3
 KEGG 3 / 63 18.4× 5.57e-4 7.27e-3 ✓ sig.
Hippo signaling pathway
FZD4, CTNNB1, SERPINE1, CTNNA1
 KEGG 4 / 157 9.9× 6.72e-4 8.36e-3 ✓ sig.
Hepatocellular carcinoma
FZD4, CTNNB1, LRP5, LRP6
 KEGG 4 / 170 9.1× 9.05e-4 1.05e-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
NDP, FZD4, LRP5, TSPAN12
 GO:0110135 4 / 4 603× 6.19e-12 2.47e-9 ✓ sig.
establishment of blood-brain barrier
NDP, FZD4, CTNNB1, LRP5
 GO:0060856 4 / 11 219× 2.03e-9 4.29e-7 ✓ sig.
extracellular matrix-cell signaling
NDP, FZD4, LRP5
 GO:0035426 3 / 4 452× 1.65e-8 2.72e-6 ✓ sig.
retinal blood vessel morphogenesis
NDP, FZD4, LRP5
 GO:0061304 3 / 6 301× 8.24e-8 1.08e-5 ✓ sig.
establishment of blood-retinal barrier
NDP, CTNNB1, LRP5
 GO:1990963 3 / 6 301× 8.24e-8 1.08e-5 ✓ sig.
Wnt signaling pathway
NDP, FZD4, CTNNB1, LRP5, LRP6, CDK14, CTNND1
 GO:0016055 7 / 232 18.2× 8.47e-8 1.10e-5 ✓ sig.
retina vasculature morphogenesis in camera-type eye
NDP, FZD4, LRP5
 GO:0061299 3 / 7 258× 1.44e-7 1.73e-5 ✓ sig.
blood vessel remodeling
NDP, AGT, NOS3, JAG1
 GO:0001974 4 / 42 57.4× 6.64e-7 6.15e-5 ✓ sig.
canonical Wnt signaling pathway
NDP, FZD4, CTNNB1, LRP5, LRP6
 GO:0060070 5 / 105 28.7× 7.70e-7 6.92e-5 ✓ sig.
retina vasculature development in camera-type eye
NDP, FZD4, LRP5
 GO:0061298 3 / 15 121× 1.86e-6 1.43e-4 ✓ sig.
embryonic digit morphogenesis
CTNNB1, LRP5, GLI3, IHH
 GO:0042733 4 / 57 42.3× 2.30e-6 1.70e-4 ✓ sig.
positive regulation of DNA-templated transcription
NDP, FZD4, RNF14, CTNNB1, LRP5, LRP6, AGT, GLI3, HLA-DRB1
 GO:0045893 9 / 778 7.0× 3.17e-6 2.19e-4 ✓ sig.
endothelial cell differentiation
NDP, FZD4, JAG1
 GO:0045446 3 / 18 100× 3.32e-6 2.27e-4 ✓ sig.
gene expression
NDP, RHO, CTNNB1, LRP5, GLI3, SOD1
 GO:0010467 6 / 269 13.4× 4.58e-6 2.96e-4 ✓ sig.
angiogenesis
NDP, FZD4, TSPAN12, NOS3, SERPINE1, JAG1
 GO:0001525 6 / 284 12.7× 6.25e-6 3.78e-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 0.250 4 7.22e-12 7.32e-11 ✓ sig.
Exudative vitreoretinopathy Retinopathy of prematurity 0.138 4 9.94e-10 8.60e-9 ✓ sig.
Exudative retinopathy Retinopathy of prematurity 0.120 3 6.42e-8 4.62e-7 ✓ sig.
Coats disease Exudative retinopathy 0.250 2 1.75e-7 1.18e-6 ✓ sig.
Coats disease Exudative vitreoretinopathy 0.154 2 5.50e-7 3.46e-6 ✓ sig.
Atrophia bulborum heritaria Exudative vitreoretinopathy 2, x-linked 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Exudative vitreoretinopathy 2, x-linked Norrie disease 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Atrophia bulborum heritaria Norrie disease 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Coats disease Exudative vitreoretinopathy 2, x-linked 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Coats disease Norrie disease 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Coats disease Retinal dystrophy with or without extraocular anomalies 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Atrophia bulborum heritaria Coats disease 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Exudative retinopathy Retinal dystrophy with or without extraocular anomalies 0.125 1 4.52e-4 8.26e-4 ✓ sig.
Atrophia bulborum heritaria Exudative retinopathy 0.125 1 4.52e-4 8.26e-4 ✓ sig.
Exudative retinopathy Exudative vitreoretinopathy 2, x-linked 0.125 1 4.52e-4 8.26e-4 ✓ sig.
Exudative retinopathy Norrie disease 0.125 1 4.52e-4 8.26e-4 ✓ sig.
Atrophia bulborum heritaria Exudative vitreoretinopathy 0.077 1 7.75e-4 1.25e-3 ✓ sig.
Exudative vitreoretinopathy Exudative vitreoretinopathy 2, x-linked 0.077 1 7.75e-4 1.25e-3 ✓ sig.
Exudative vitreoretinopathy Norrie disease 0.077 1 7.75e-4 1.25e-3 ✓ sig.
Exudative vitreoretinopathy Retinal dystrophy with or without extraocular anomalies 0.077 1 7.75e-4 1.25e-3 ✓ sig.