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 259

7 diseases · 12 shared-gene connections
7 Diseases
29 Unique genes
0.188 Avg. similarity score
Hypercalcemia 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 ⇵
Hypercalcemia 6 6 13
Bone resorption 3 3 10
Hypercalciuria 3 3 9
Idiopathic infantile hypercalcemia 3 3 4
Kidney and ureter calculus 3 3 4
Osteolysis 3 3 7
autosomal recessive osteopetrosis 2 3 3 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
CYP24A1 4 / 7 Hypercalcemia, Hypercalciuria, Idiopathic infantile hypercalcemia, Kidney and ureter calculus
SLC34A1 4 / 7 Hypercalcemia, Hypercalciuria, Idiopathic infantile hypercalcemia, Kidney and ureter calculus
TNFSF11 4 / 7 autosomal recessive osteopetrosis 2, Bone resorption, Hypercalcemia, Osteolysis
KL 3 / 7 Hypercalcemia, Hypercalciuria, Idiopathic infantile hypercalcemia
PTH 3 / 7 Bone resorption, Hypercalcemia, Hypercalciuria
PTHLH 3 / 7 Bone resorption, Hypercalcemia, Osteolysis
TNFRSF11B 3 / 7 Bone resorption, Hypercalcemia, Osteolysis
CASR 2 / 7 Hypercalcemia, Kidney and ureter calculus
TNF 2 / 7 Hypercalcemia, Osteolysis
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 ⇵
Parathyroid hormone synthesis, secretion and action
PTH, PTHLH, TNFSF11, CASR, CYP24A1, SLC34A1, TRPV5, CYP27B1, KL
 KEGG 9 / 115 32.4× 4.20e-12 8.09e-10 ✓ sig.
ADORA2B mediated anti-inflammatory cytokines production
PTH, PTHLH, CALCA, CALCR, IL6, POMC
 Reactome 6 / 128 19.4× 5.06e-7 2.71e-5 ✓ sig.
Rheumatoid arthritis
CXCL2, PTH, TNFSF11, IL6, TNF
 KEGG 5 / 95 21.8× 2.85e-6 1.19e-4 ✓ sig.
Hormone signaling
GHRL, PTH, PTHLH, CALCA, CALCR, POMC
 KEGG 6 / 219 11.3× 1.15e-5 3.76e-4 ✓ sig.
G alpha (s) signalling events
PTH, PTHLH, CALCA, CALCR, POMC
 Reactome 5 / 140 14.8× 1.90e-5 5.75e-4 ✓ sig.
Endogenous sterols
AHR, CYP19A1, POMC
 Reactome 3 / 25 49.7× 2.81e-5 7.89e-4 ✓ sig.
Cytokine-cytokine receptor interaction
BMP7, CXCL2, TNFRSF11B, TNFSF11, IL6, TNF
 KEGG 6 / 298 8.3× 6.51e-5 1.58e-3 ✓ sig.
NOD-like receptor signaling pathway
CXCL2, CASR, IL6, TNF, ANTXR2
 KEGG 5 / 187 11.1× 7.60e-5 1.79e-3 ✓ sig.
Vitamins
CYP24A1, CYP27B1
 Reactome 2 / 6 138× 8.39e-5 1.95e-3 ✓ sig.
Interleukin-10 signaling
CXCL2, IL6, TNF
 Reactome 3 / 47 26.4× 1.91e-4 3.77e-3 ✓ sig.
Calcitonin-like ligand receptors
CALCA, CALCR
 Reactome 2 / 10 82.8× 2.50e-4 4.65e-3 ✓ sig.
Endocrine and other factor-regulated calcium reabsorption
PTH, TRPV5, KL
 KEGG 3 / 53 23.4× 2.73e-4 4.99e-3 ✓ sig.
Vitamin D (calciferol) metabolism
CYP24A1, CYP27B1
 Reactome 2 / 11 75.3× 3.05e-4 5.44e-3 ✓ sig.
Legionellosis
CXCL2, IL6, TNF
 KEGG 3 / 56 22.2× 3.22e-4 5.67e-3 ✓ sig.
Osteoclast differentiation
TNFRSF11B, TNFSF11, CALCR, TNF
 KEGG 4 / 142 11.7× 3.54e-4 6.10e-3 ✓ 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 vitamin D
BMP7, PTH, CYP24A1, CYP27B1, KL, SPP1
 GO:0033280 6 / 21 184× 4.29e-13 2.11e-10 ✓ sig.
ossification
BMP7, COL2A1, TNFSF11, CASR, SLC34A1, CALCR, IBSP, SPP1
 GO:0001503 8 / 110 46.9× 4.31e-12 1.71e-9 ✓ sig.
calcium ion homeostasis
PTH, TNFSF11, TRPV5, CYP27B1, KL
 GO:0055074 5 / 42 76.7× 5.12e-9 9.51e-7 ✓ sig.
adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway
PTH, PTHLH, CASR
 GO:0140582 3 / 5 387× 3.35e-8 4.82e-6 ✓ sig.
adenylate cyclase-activating G protein-coupled receptor signaling pathway
PTH, PTHLH, CASR, ADCY10, CALCA, CALCR
 GO:0007189 6 / 161 24.0× 1.50e-7 1.71e-5 ✓ sig.
response to fibroblast growth factor
PTH, CASR, KL
 GO:0071774 3 / 11 176× 5.50e-7 5.07e-5 ✓ sig.
cellular response to vitamin D
CASR, CYP24A1, CYP27B1
 GO:0071305 3 / 13 149× 9.51e-7 7.98e-5 ✓ sig.
bone mineralization
PTH, PTHLH, CYP27B1, IBSP
 GO:0030282 4 / 56 46.0× 1.62e-6 1.22e-4 ✓ sig.
positive regulation of estradiol secretion
CYP19A1, SPP1
 GO:2000866 2 / 2 644× 2.33e-6 1.62e-4 ✓ sig.
skeletal system development
BMP7, COL2A1, PTH, PTHLH, TNFRSF11B
 GO:0001501 5 / 151 21.3× 3.27e-6 2.14e-4 ✓ sig.
decidualization
GHRL, CYP27B1, SPP1
 GO:0046697 3 / 25 77.3× 7.55e-6 4.18e-4 ✓ sig.
monocyte chemotaxis
TNFSF11, CALCA, IL6
 GO:0002548 3 / 26 74.4× 8.53e-6 4.60e-4 ✓ sig.
positive regulation of gene expression
BMP7, PTH, TNFSF11, CASR, CALCR, IL6, TNF
 GO:0010628 7 / 504 8.9× 9.28e-6 4.93e-4 ✓ sig.
negative regulation of neurogenesis
BMP7, IL6, TNF
 GO:0050768 3 / 30 64.4× 1.33e-5 6.50e-4 ✓ sig.
response to macrophage colony-stimulating factor
TNF, SPP1
 GO:0036005 2 / 4 322× 1.39e-5 6.76e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hypercalcemia Osteolysis 0.235 4 1.07e-11 1.24e-10 ✓ sig.
Hypercalcemia Hypercalciuria 0.211 4 3.84e-11 4.20e-10 ✓ sig.
Bone resorption Hypercalcemia 0.200 4 6.39e-11 6.87e-10 ✓ sig.
Hypercalciuria Idiopathic infantile hypercalcemia 0.273 3 5.52e-10 5.42e-9 ✓ sig.
Hypercalcemia Idiopathic infantile hypercalcemia 0.200 3 1.88e-9 1.75e-8 ✓ sig.
Hypercalcemia Kidney and ureter calculus 0.200 3 1.88e-9 1.75e-8 ✓ sig.
Bone resorption Osteolysis 0.200 3 6.89e-9 6.09e-8 ✓ sig.
Idiopathic infantile hypercalcemia Kidney and ureter calculus 0.286 2 3.04e-7 2.06e-6 ✓ sig.
Hypercalciuria Kidney and ureter calculus 0.167 2 1.82e-6 1.08e-5 ✓ sig.
autosomal recessive osteopetrosis 2 Osteolysis 0.125 1 4.55e-4 9.55e-4 ✓ sig.
autosomal recessive osteopetrosis 2 Bone resorption 0.091 1 6.49e-4 1.22e-3 ✓ sig.
autosomal recessive osteopetrosis 2 Hypercalcemia 0.071 1 8.44e-4 1.48e-3 ✓ sig.