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 265

7 diseases · 12 shared-gene connections
7 Diseases
20 Unique genes
0.196 Avg. similarity score
Osteopetrosis Most-connected disease (6 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 ⇵
Osteopetrosis 6 6 17
Osteosclerosis 4 4 8
autosomal dominant osteopetrosis 2 4 4 1
autosomal recessive osteopetrosis 4 4 4 1
hypopigmentation, organomegaly, and delayed myelination and development 4 4 1
autosomal recessive osteopetrosis 5 1 1 1
autosomal recessive osteopetrosis 8 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
CLCN7 5 / 7 autosomal dominant osteopetrosis 2, autosomal recessive osteopetrosis 4, hypopigmentation, organomegaly, and delayed myelination and development, Osteopetrosis and 1 more
LRP5 2 / 7 Osteopetrosis, Osteosclerosis
OSTM1 2 / 7 autosomal recessive osteopetrosis 5, Osteopetrosis
SNX10 2 / 7 autosomal recessive osteopetrosis 8, Osteopetrosis
TCIRG1 2 / 7 Osteopetrosis, Osteosclerosis
TNFRSF11A 2 / 7 Osteopetrosis, Osteosclerosis
TNFSF11 2 / 7 Osteopetrosis, Osteosclerosis
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 ⇵
Collecting duct acid secretion
TCIRG1, CA2, CLCNKB
 KEGG 3 / 28 64.3× 1.26e-5 4.07e-4 ✓ sig.
Stimuli-sensing channels
CLCN7, OSTM1, CLCNKB
 Reactome 3 / 79 22.8× 2.88e-4 5.20e-3 ✓ sig.
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
TNFSF11, TNFRSF11A
 Reactome 2 / 18 66.7× 3.97e-4 6.66e-3 ✓ sig.
Rheumatoid arthritis
TCIRG1, TNFSF11, TNFRSF11A
 KEGG 3 / 95 19.0× 4.96e-4 7.92e-3 ✓ sig.
Disassembly of the destruction complex and recruitment of AXIN to the membrane
LRP5, CTNNB1
 Reactome 2 / 30 40.0× 1.11e-3 1.47e-2 ✓ sig.
Breast cancer
LRP5, TNFSF11, CTNNB1
 KEGG 3 / 148 12.2× 1.79e-3 2.11e-2 ✓ sig.
Intracellular metabolism of fatty acids regulates insulin secretion
CD36
 Reactome 1 / 3 200× 4.99e-3 4.37e-2 ✓ sig.
TNFR2 non-canonical NF-kB pathway
TNFSF11, TNFRSF11A
 Reactome 2 / 69 17.4× 5.78e-3 4.83e-2 ✓ sig.
Prolactin signaling pathway
TNFSF11, TNFRSF11A
 KEGG 2 / 71 16.9× 6.11e-3 5.00e-2 ✓ sig.
Toll Like Receptor TLR6:TLR2 Cascade
CD36
 Reactome 1 / 4 150× 6.65e-3 5.28e-2
Gastric acid secretion
CA2, SLC4A2
 KEGG 2 / 76 15.8× 6.97e-3 5.45e-2
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production
CTNNB1
 Reactome 1 / 5 120× 8.30e-3 6.10e-2
Scavenging by Class B Receptors
CD36
 Reactome 1 / 5 120× 8.30e-3 6.10e-2
Bile secretion
CA2, SLC4A2
 KEGG 2 / 90 13.3× 9.67e-3 6.73e-2
Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling
LRP5
 Reactome 1 / 6 100× 9.95e-3 6.82e-2

Enriched GO Terms (Biological Process, a second line of biological evidence)

GO term ⇵ GO ID ⇵ Overlap genes ⇵ Fold enrichment ⇵ P-value ⇵ FDR q-value ⇵
osteoclast differentiation
SNX10, TCIRG1, TNFSF11, OSTM1, TNFRSF11A, SLC4A2, CTNNB1
 GO:0030316 7 / 49 133× 4.12e-14 2.42e-11 ✓ sig.
positive regulation of bone resorption
TNFSF11, PLEKHM1, TNFRSF11A, LTBP3
 GO:0045780 4 / 15 249× 1.29e-9 2.82e-7 ✓ sig.
tooth eruption
SNX10, TCIRG1, TNFSF11
 GO:0044691 3 / 5 561× 1.05e-8 1.78e-6 ✓ sig.
bone resorption
SNX10, TCIRG1, TNFSF11, CTNNB1
 GO:0045453 4 / 26 144× 1.40e-8 2.30e-6 ✓ sig.
transepithelial chloride transport
CLCN7, OSTM1, CLCNKB
 GO:0030321 3 / 9 311× 8.77e-8 1.08e-5 ✓ sig.
regulation of osteoblast differentiation
LRP5, TCIRG1, CTNNB1
 GO:0045667 3 / 17 165× 7.06e-7 6.27e-5 ✓ sig.
bone remodeling
LRP5, SNX10, LTBP3
 GO:0046849 3 / 18 156× 8.47e-7 7.24e-5 ✓ sig.
positive regulation of fever generation by positive regulation of prostaglandin secretion
TNFSF11, TNFRSF11A
 GO:0071812 2 / 2 934× 1.09e-6 8.87e-5 ✓ sig.
osteoclast proliferation
TCIRG1, TNFSF11
 GO:0002158 2 / 5 374× 1.09e-5 5.55e-4 ✓ sig.
establishment of blood-retinal barrier
LRP5, CTNNB1
 GO:1990963 2 / 6 311× 1.63e-5 7.66e-4 ✓ sig.
positive regulation of homotypic cell-cell adhesion
TNFSF11, CTNNB1
 GO:0034112 2 / 7 267× 2.28e-5 9.93e-4 ✓ sig.
establishment of blood-brain barrier
LRP5, CTNNB1
 GO:0060856 2 / 11 170× 5.95e-5 2.04e-3 ✓ sig.
regulation of osteoclast differentiation
TNFSF11, CTNNB1
 GO:0045670 2 / 14 133× 9.83e-5 2.98e-3 ✓ sig.
mammary gland alveolus development
TNFSF11, TNFRSF11A
 GO:0060749 2 / 17 110× 1.47e-4 4.02e-3 ✓ sig.
gastrulation with mouth forming second
LRP5, CTNNB1
 GO:0001702 2 / 17 110× 1.47e-4 4.02e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Osteopetrosis Osteosclerosis 0.238 5 4.80e-14 6.73e-13 ✓ sig.
autosomal dominant osteopetrosis 2 hypopigmentation, organomegaly, and delayed myelination and development 0.500 1 6.49e-5 2.34e-4 ✓ sig.
autosomal dominant osteopetrosis 2 autosomal recessive osteopetrosis 4 0.500 1 6.49e-5 2.34e-4 ✓ sig.
autosomal recessive osteopetrosis 4 hypopigmentation, organomegaly, and delayed myelination and development 0.500 1 6.49e-5 2.34e-4 ✓ sig.
autosomal dominant osteopetrosis 2 Osteosclerosis 0.111 1 5.20e-4 1.04e-3 ✓ sig.
autosomal recessive osteopetrosis 4 Osteosclerosis 0.111 1 5.20e-4 1.04e-3 ✓ sig.
hypopigmentation, organomegaly, and delayed myelination and development Osteosclerosis 0.111 1 5.20e-4 1.04e-3 ✓ sig.
autosomal dominant osteopetrosis 2 Osteopetrosis 0.056 1 1.10e-3 1.81e-3 ✓ sig.
autosomal recessive osteopetrosis 4 Osteopetrosis 0.056 1 1.10e-3 1.81e-3 ✓ sig.
autosomal recessive osteopetrosis 5 Osteopetrosis 0.056 1 1.10e-3 1.81e-3 ✓ sig.
autosomal recessive osteopetrosis 8 Osteopetrosis 0.056 1 1.10e-3 1.81e-3 ✓ sig.
hypopigmentation, organomegaly, and delayed myelination and development Osteopetrosis 0.056 1 1.10e-3 1.81e-3 ✓ sig.