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 91

12 diseases · 23 shared-gene connections
12 Diseases
24 Unique genes
0.249 Avg. similarity score
Alport syndrome, x-linked Most-connected disease (8 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 ⇵
Alport syndrome, x-linked 8 8 4
Alport syndrome 6 6 4
Digenic alport syndrome 6 6 3
Diffuse mesangial sclerosis 4 4 2
Hematuria 4 4 11
Intellectual disability, autism, speech apraxia, craniofacial dysmorphism syndrome 4 4 2
Leiomyoma 4 4 10
X-linked diffuse leiomyomatosis with alport syndrome 4 4 2
hearing loss, X-linked 6 3 3 1
Diaphragm disease 1 1 2
Intellectual developmental disorder autism speech dysmorphic 1 1 1
Midface hypoplasia-hearing impairment-elliptocytosis-nephrocalcinosis syndrome 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
COL4A5 6 / 12 Alport syndrome, Alport syndrome, x-linked, Digenic alport syndrome, Hematuria and 2 more
COL4A3 5 / 12 Alport syndrome, Alport syndrome, x-linked, Digenic alport syndrome, Hematuria and 1 more
COL4A4 5 / 12 Alport syndrome, Alport syndrome, x-linked, Diffuse mesangial sclerosis, Digenic alport syndrome and 1 more
COL4A6 4 / 12 Alport syndrome, x-linked, hearing loss, X-linked 6, Leiomyoma, X-linked diffuse leiomyomatosis with alport syndrome
AMMECR1 2 / 12 Alport syndrome, Midface hypoplasia-hearing impairment-elliptocytosis-nephrocalcinosis syndrome
CHD1 2 / 12 Intellectual developmental disorder autism speech dysmorphic, Intellectual disability, autism, speech apraxia, craniofacial dysmorphism syndrome
WNT5B 2 / 12 Diaphragm disease, Leiomyoma
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 ⇵
Laminin interactions
COL4A3, COL4A4, COL4A5, LAMB2, COL4A6
 Reactome 5 / 28 89.4× 1.95e-9 2.01e-7 ✓ sig.
Human papillomavirus infection
COL4A3, COL4A4, COL4A5, WNT3A, WNT5B, LAMB2, EGFR, TSC2, COL4A6
 KEGG 9 / 333 13.5× 7.88e-9 7.12e-7 ✓ sig.
Extracellular matrix organization
COL4A3, COL4A4, COL4A5, COL4A6
 Reactome 4 / 15 133× 1.65e-8 1.35e-6 ✓ sig.
Anchoring fibril formation
COL4A3, COL4A4, COL4A5, COL4A6
 Reactome 4 / 15 133× 1.65e-8 1.35e-6 ✓ sig.
Pathways in cancer
COL4A3, COL4A4, COL4A5, WNT3A, WNT5B, LAMB2, EGFR, ESR1, SMAD3, COL4A6
 KEGG 10 / 533 9.4× 3.05e-8 2.32e-6 ✓ sig.
Crosslinking of collagen fibrils
COL4A3, COL4A4, COL4A5, COL4A6
 Reactome 4 / 18 111× 3.68e-8 2.72e-6 ✓ sig.
Non-integrin membrane-ECM interactions
COL4A3, COL4A4, COL4A5, COL4A6
 Reactome 4 / 24 83.4× 1.27e-7 8.04e-6 ✓ sig.
ECM-receptor interaction
COL4A3, COL4A4, COL4A5, LAMB2, COL4A6
 KEGG 5 / 89 28.1× 7.59e-7 3.84e-5 ✓ sig.
Small cell lung cancer
COL4A3, COL4A4, COL4A5, LAMB2, COL4A6
 KEGG 5 / 93 26.9× 9.45e-7 4.64e-5 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
COL4A3, COL4A4, COL4A5, SMAD3, COL4A6
 KEGG 5 / 101 24.8× 1.43e-6 6.65e-5 ✓ sig.
Amoebiasis
COL4A3, COL4A4, COL4A5, LAMB2, COL4A6
 KEGG 5 / 103 24.3× 1.57e-6 7.19e-5 ✓ sig.
Collagen chain trimerization
COL4A3, COL4A4, COL4A5, COL4A6
 Reactome 4 / 44 45.5× 1.58e-6 7.21e-5 ✓ sig.
Focal adhesion
COL4A3, COL4A4, COL4A5, LAMB2, EGFR, COL4A6
 KEGG 6 / 203 14.8× 2.26e-6 9.78e-5 ✓ sig.
Assembly of collagen fibrils and other multimeric structures
COL4A3, COL4A4, COL4A5, COL4A6
 Reactome 4 / 51 39.2× 2.88e-6 1.20e-4 ✓ sig.
Collagen degradation
COL4A3, COL4A4, COL4A5, COL4A6
 Reactome 4 / 52 38.5× 3.11e-6 1.28e-4 ✓ 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 ⇵
cellular response to estradiol stimulus
EGFR, ESR1, GPER1, SFRP1
 GO:0071392 4 / 36 86.5× 1.20e-7 1.40e-5 ✓ sig.
collagen-activated tyrosine kinase receptor signaling pathway
COL4A3, COL4A5, COL4A6
 GO:0038063 3 / 12 195× 4.06e-7 3.93e-5 ✓ sig.
positive regulation of cell migration
WNT5B, F7, PLAU, EGFR, GPER1, SMAD3
 GO:0030335 6 / 292 16.0× 1.47e-6 1.13e-4 ✓ sig.
response to genistein
CYP1A1, F7
 GO:0033595 2 / 3 519× 4.74e-6 2.88e-4 ✓ sig.
positive regulation of canonical Wnt signaling pathway
WNT3A, EGFR, SFRP1, SMAD3
 GO:0090263 4 / 115 27.1× 1.32e-5 6.46e-4 ✓ sig.
response to 2,3,7,8-tetrachlorodibenzodioxine
CYP1A1, F7
 GO:1904612 2 / 5 311× 1.58e-5 7.48e-4 ✓ sig.
regulation of branching involved in prostate gland morphogenesis
ESR1, SFRP1
 GO:0060687 2 / 5 311× 1.58e-5 7.48e-4 ✓ sig.
negative regulation of B cell differentiation
INHBA, SFRP1
 GO:0045578 2 / 5 311× 1.58e-5 7.48e-4 ✓ sig.
negative regulation of cell population proliferation
COL4A3, GPER1, INHBA, SFRP1, SMAD3, TSC2
 GO:0008285 6 / 444 10.5× 1.63e-5 7.66e-4 ✓ sig.
steroid hormone receptor signaling pathway
ESR1, GPER1
 GO:0043401 2 / 6 260× 2.36e-5 1.02e-3 ✓ sig.
prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis
ESR1, SFRP1
 GO:0060527 2 / 7 222× 3.31e-5 1.32e-3 ✓ sig.
somitogenesis
WNT3A, SFRP1, SMAD3
 GO:0001756 3 / 50 46.7× 3.51e-5 1.38e-3 ✓ sig.
positive regulation of non-canonical Wnt signaling pathway
WNT5B, SFRP1
 GO:2000052 2 / 8 195× 4.41e-5 1.64e-3 ✓ sig.
negative regulation of fat cell differentiation
WNT3A, GPER1, SMAD3
 GO:0045599 3 / 57 41.0× 5.20e-5 1.86e-3 ✓ sig.
extrinsic apoptotic signaling pathway
INHBA, SFRP1, SMAD3
 GO:0097191 3 / 57 41.0× 5.20e-5 1.86e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Alport syndrome Digenic alport syndrome 0.600 3 6.58e-12 7.74e-11 ✓ sig.
Alport syndrome, x-linked Digenic alport syndrome 0.600 3 6.58e-12 7.74e-11 ✓ sig.
Alport syndrome Alport syndrome, x-linked 0.500 3 2.63e-11 2.94e-10 ✓ sig.
Digenic alport syndrome Hematuria 0.250 3 2.71e-10 2.74e-9 ✓ sig.
Alport syndrome, x-linked Hematuria 0.231 3 1.08e-9 1.04e-8 ✓ sig.
Alport syndrome Hematuria 0.231 3 1.08e-9 1.04e-8 ✓ sig.
Alport syndrome, x-linked X-linked diffuse leiomyomatosis with alport syndrome 0.400 2 5.06e-8 3.92e-7 ✓ sig.
Leiomyoma X-linked diffuse leiomyomatosis with alport syndrome 0.182 2 3.80e-7 2.53e-6 ✓ sig.
Alport syndrome, x-linked Leiomyoma 0.154 2 2.28e-6 1.33e-5 ✓ sig.
Intellectual developmental disorder autism speech dysmorphic Intellectual disability, autism, speech apraxia, craniofacial dysmorphism syndrome 0.333 1 1.30e-4 3.90e-4 ✓ sig.
hearing loss, X-linked 6 X-linked diffuse leiomyomatosis with alport syndrome 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Alport syndrome, x-linked hearing loss, X-linked 6 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Alport syndrome Midface hypoplasia-hearing impairment-elliptocytosis-nephrocalcinosis syndrome 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Digenic alport syndrome Intellectual disability, autism, speech apraxia, craniofacial dysmorphism syndrome 0.200 1 3.90e-4 8.52e-4 ✓ sig.
Diffuse mesangial sclerosis Digenic alport syndrome 0.200 1 3.90e-4 8.52e-4 ✓ sig.
Digenic alport syndrome X-linked diffuse leiomyomatosis with alport syndrome 0.200 1 3.90e-4 8.52e-4 ✓ sig.
Alport syndrome, x-linked Diffuse mesangial sclerosis 0.167 1 5.19e-4 1.04e-3 ✓ sig.
Alport syndrome Intellectual disability, autism, speech apraxia, craniofacial dysmorphism syndrome 0.167 1 5.19e-4 1.04e-3 ✓ sig.
Alport syndrome, x-linked Intellectual disability, autism, speech apraxia, craniofacial dysmorphism syndrome 0.167 1 5.19e-4 1.04e-3 ✓ sig.
Alport syndrome Diffuse mesangial sclerosis 0.167 1 5.19e-4 1.04e-3 ✓ sig.
hearing loss, X-linked 6 Leiomyoma 0.091 1 6.49e-4 1.22e-3 ✓ sig.
Diaphragm disease Leiomyoma 0.083 1 1.30e-3 2.04e-3 ✓ sig.
Diffuse mesangial sclerosis Hematuria 0.077 1 1.43e-3 2.21e-3 ✓ sig.