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 163

9 diseases · 20 shared-gene connections
9 Diseases
23 Unique genes
0.294 Avg. similarity score
Idiopathic infantile hypercalcemia Most-connected disease (7 links)
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Disease Searched: Idiopathic infantile hypercalcemia 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 ⇵
Idiopathic infantile hypercalcemia 7 7 4
Cerebral embolism 5 5 1
Hypercalcemic tumoral calcinosis 5 5 3
Hyperphosphatemic tumoral calcinosis 5 5 3
Intracranial embolism 5 5 1
Tumoral calcinosis 4 4 4
Hypercalcemia 3 3 13
Hypercalciuria 3 3 9
Kidney and ureter calculus 3 3 4

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

Gene ⇵ Member diseases ⇵ Linked diseases
KL 8 / 9 Cerebral embolism, Hypercalcemia, Hypercalcemic tumoral calcinosis, Hypercalciuria and 4 more
CYP24A1 4 / 9 Hypercalcemia, Hypercalciuria, Idiopathic infantile hypercalcemia, Kidney and ureter calculus
SLC34A1 4 / 9 Hypercalcemia, Hypercalciuria, Idiopathic infantile hypercalcemia, Kidney and ureter calculus
FGF23 3 / 9 Hypercalcemic tumoral calcinosis, Hyperphosphatemic tumoral calcinosis, Tumoral calcinosis
GALNT3 3 / 9 Hypercalcemic tumoral calcinosis, Hyperphosphatemic tumoral calcinosis, Tumoral calcinosis
CASR 2 / 9 Hypercalcemia, Kidney and ureter calculus
PTH 2 / 9 Hypercalcemia, Hypercalciuria
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
CASR, CYP24A1, SLC34A1, KL, FGF23, TRPV5, CYP27B1, PTH, PTHLH, TNFSF11
 KEGG 10 / 115 45.4× 4.48e-15 1.37e-12 ✓ sig.
ADORA2B mediated anti-inflammatory cytokines production
CALCA, CALCR, IL6, PTH, PTHLH, POMC
 Reactome 6 / 128 24.5× 1.13e-7 7.04e-6 ✓ sig.
G alpha (s) signalling events
CALCA, CALCR, PTH, PTHLH, POMC
 Reactome 5 / 140 18.6× 5.69e-6 2.05e-4 ✓ sig.
FGFR1c and Klotho ligand binding and activation
KL, FGF23
 Reactome 2 / 3 348× 1.05e-5 3.39e-4 ✓ sig.
Rheumatoid arthritis
IL6, PTH, TNF, TNFSF11
 KEGG 4 / 95 22.0× 2.90e-5 7.95e-4 ✓ sig.
Hormone signaling
CALCA, CALCR, PTH, PTHLH, POMC
 KEGG 5 / 219 11.9× 4.96e-5 1.23e-3 ✓ sig.
Vitamins
CYP24A1, CYP27B1
 Reactome 2 / 6 174× 5.24e-5 1.29e-3 ✓ sig.
Endocrine and other factor-regulated calcium reabsorption
KL, TRPV5, PTH
 KEGG 3 / 53 29.6× 1.35e-4 2.78e-3 ✓ sig.
Osteoclast differentiation
CALCR, TNF, TNFRSF11B, TNFSF11
 KEGG 4 / 142 14.7× 1.39e-4 2.85e-3 ✓ sig.
Calcitonin-like ligand receptors
CALCA, CALCR
 Reactome 2 / 10 104× 1.56e-4 3.13e-3 ✓ sig.
Vitamin D (calciferol) metabolism
CYP24A1, CYP27B1
 Reactome 2 / 11 94.9× 1.91e-4 3.67e-3 ✓ sig.
FGFR3c ligand binding and activation
FGF23, GALNT3
 Reactome 2 / 13 80.3× 2.70e-4 4.83e-3 ✓ sig.
Phospholipase C-mediated cascade: FGFR1
KL, FGF23
 Reactome 2 / 16 65.3× 4.14e-4 6.81e-3 ✓ sig.
Class B/2 (Secretin family receptors)
PTH, PTHLH
 Reactome 2 / 18 58.0× 5.27e-4 8.19e-3 ✓ sig.
Downstream signaling of activated FGFR1
KL, FGF23
 Reactome 2 / 18 58.0× 5.27e-4 8.19e-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 ⇵
calcium ion homeostasis
KL, FGF23, TRPV5, CYP27B1, PTH, TNFSF11
 GO:0055074 6 / 42 116× 8.71e-12 3.25e-9 ✓ sig.
cellular response to vitamin D
CASR, CYP24A1, FGF23, CYP27B1
 GO:0071305 4 / 13 250× 1.24e-9 2.69e-7 ✓ sig.
vitamin D catabolic process
CYP24A1, FGF23, CYP27B1
 GO:0042369 3 / 4 609× 6.51e-9 1.16e-6 ✓ sig.
response to vitamin D
CYP24A1, KL, CYP27B1, PTH
 GO:0033280 4 / 21 155× 1.03e-8 1.73e-6 ✓ sig.
adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway
CASR, PTH, PTHLH
 GO:0140582 3 / 5 487× 1.63e-8 2.58e-6 ✓ sig.
adenylate cyclase-activating G protein-coupled receptor signaling pathway
CASR, ADCY10, CALCA, CALCR, PTH, PTHLH
 GO:0007189 6 / 161 30.3× 3.33e-8 4.72e-6 ✓ sig.
response to fibroblast growth factor
CASR, KL, PTH
 GO:0071774 3 / 11 222× 2.67e-7 2.76e-5 ✓ sig.
vitamin D metabolic process
CYP24A1, FGF23, CYP27B1
 GO:0042359 3 / 12 203× 3.56e-7 3.50e-5 ✓ sig.
phosphate ion homeostasis
SLC34A1, FGF23, PTH
 GO:0055062 3 / 15 162× 7.34e-7 6.41e-5 ✓ sig.
positive regulation of ERK1 and ERK2 cascade
CASR, FGF23, CALCR, TNF, TNFSF11
 GO:0070374 5 / 201 20.2× 3.94e-6 2.49e-4 ✓ sig.
monocyte chemotaxis
CALCA, IL6, TNFSF11
 GO:0002548 3 / 26 93.7× 4.16e-6 2.60e-4 ✓ sig.
amylin receptor 1 signaling pathway
CALCA, CALCR
 GO:0150059 2 / 4 406× 8.68e-6 4.72e-4 ✓ sig.
amylin receptor 2 signaling pathway
CALCA, CALCR
 GO:0150060 2 / 4 406× 8.68e-6 4.72e-4 ✓ sig.
cAMP metabolic process
PTH, PTHLH
 GO:0046058 2 / 4 406× 8.68e-6 4.72e-4 ✓ sig.
small molecule biosynthetic process
CYP24A1, CYP27B1
 GO:0044283 2 / 4 406× 8.68e-6 4.72e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hypercalcemic tumoral calcinosis Hyperphosphatemic tumoral calcinosis 0.750 3 1.64e-12 1.92e-11 ✓ sig.
Hyperphosphatemic tumoral calcinosis Tumoral calcinosis 0.600 3 6.58e-12 7.31e-11 ✓ sig.
Hypercalcemic tumoral calcinosis Tumoral calcinosis 0.600 3 6.58e-12 7.31e-11 ✓ sig.
Hypercalcemia Hypercalciuria 0.211 4 3.84e-11 3.96e-10 ✓ sig.
Hypercalciuria Idiopathic infantile hypercalcemia 0.273 3 5.52e-10 5.12e-9 ✓ sig.
Hypercalcemia Idiopathic infantile hypercalcemia 0.200 3 1.88e-9 1.65e-8 ✓ sig.
Hypercalcemia Kidney and ureter calculus 0.200 3 1.88e-9 1.65e-8 ✓ sig.
Idiopathic infantile hypercalcemia Kidney and ureter calculus 0.286 2 3.04e-7 1.95e-6 ✓ sig.
Hypercalciuria Kidney and ureter calculus 0.167 2 1.82e-6 1.02e-5 ✓ sig.
Cerebral embolism Intracranial embolism 0.500 1 6.49e-5 2.33e-4 ✓ sig.
Cerebral embolism Hyperphosphatemic tumoral calcinosis 0.250 1 1.95e-4 5.35e-4 ✓ sig.
Hyperphosphatemic tumoral calcinosis Intracranial embolism 0.250 1 1.95e-4 5.35e-4 ✓ sig.
Hypercalcemic tumoral calcinosis Intracranial embolism 0.250 1 1.95e-4 5.35e-4 ✓ sig.
Cerebral embolism Hypercalcemic tumoral calcinosis 0.250 1 1.95e-4 5.35e-4 ✓ sig.
Cerebral embolism Tumoral calcinosis 0.200 1 2.60e-4 6.51e-4 ✓ sig.
Cerebral embolism Idiopathic infantile hypercalcemia 0.200 1 2.60e-4 6.51e-4 ✓ sig.
Idiopathic infantile hypercalcemia Intracranial embolism 0.200 1 2.60e-4 6.51e-4 ✓ sig.
Intracranial embolism Tumoral calcinosis 0.200 1 2.60e-4 6.51e-4 ✓ sig.
Hypercalcemic tumoral calcinosis Idiopathic infantile hypercalcemia 0.143 1 7.79e-4 1.40e-3 ✓ sig.
Hyperphosphatemic tumoral calcinosis Idiopathic infantile hypercalcemia 0.143 1 7.79e-4 1.40e-3 ✓ sig.