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 89

12 diseases · 17 shared-gene connections
12 Diseases
49 Unique genes
0.175 Avg. similarity score
Idiopathic infantile hypercalcemia Most-connected disease (5 links)
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Disease Searched: 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 5 5 4
Cerebral embolism 3 3 1
Hypercalcemia 3 3 13
Hypercalciuria 3 3 9
Infertility 3 3 8
Intracranial embolism 3 3 1
Kidney and ureter calculus 3 3 4
Male infertility large polyploid spermatozoa 3 3 9
Male infertility spermatogenesis disorder 3 3 16
spermatogenic failure 5 3 3 1
spermatogenic failure 39 1 1 1
spermatogenic failure 46 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
KL 6 / 12 Cerebral embolism, Hypercalcemia, Hypercalciuria, Idiopathic infantile hypercalcemia and 2 more
AURKC 4 / 12 Infertility, Male infertility large polyploid spermatozoa, Male infertility spermatogenesis disorder, spermatogenic failure 5
CYP24A1 4 / 12 Hypercalcemia, Hypercalciuria, Idiopathic infantile hypercalcemia, Kidney and ureter calculus
SLC34A1 4 / 12 Hypercalcemia, Hypercalciuria, Idiopathic infantile hypercalcemia, Kidney and ureter calculus
CASR 2 / 12 Hypercalcemia, Kidney and ureter calculus
DNAH17 2 / 12 Male infertility spermatogenesis disorder, spermatogenic failure 39
DNAH8 2 / 12 Male infertility large polyploid spermatozoa, spermatogenic failure 46
DNHD1 2 / 12 Male infertility large polyploid spermatozoa, Male infertility spermatogenesis disorder
PTH 2 / 12 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, TRPV5, CYP27B1, PTH, PTHLH, TNFSF11
 KEGG 9 / 115 19.2× 7.35e-10 8.17e-8 ✓ sig.
ADORA2B mediated anti-inflammatory cytokines production
CALCA, CALCR, IL6, PTH, PTHLH, POMC, PTGER2
 Reactome 7 / 128 13.4× 7.84e-7 3.92e-5 ✓ sig.
G alpha (s) signalling events
CALCA, CALCR, PTH, PTHLH, POMC, PTGER2
 Reactome 6 / 140 10.5× 2.09e-5 6.32e-4 ✓ sig.
Vitamins
CYP24A1, CYP27B1
 Reactome 2 / 6 81.7× 2.42e-4 4.59e-3 ✓ sig.
Hormone signaling
CALCA, CALCR, PTH, PTHLH, POMC, LEPR
 KEGG 6 / 219 6.7× 2.49e-4 4.70e-3 ✓ sig.
Rheumatoid arthritis
IL6, PTH, TNF, TNFSF11
 KEGG 4 / 95 10.3× 5.93e-4 9.29e-3 ✓ sig.
Calcitonin-like ligand receptors
CALCA, CALCR
 Reactome 2 / 10 49.0× 7.19e-4 1.08e-2 ✓ sig.
Vitamin D (calciferol) metabolism
CYP24A1, CYP27B1
 Reactome 2 / 11 44.6× 8.76e-4 1.26e-2 ✓ sig.
Endocrine and other factor-regulated calcium reabsorption
KL, TRPV5, PTH
 KEGG 3 / 53 13.9× 1.30e-3 1.69e-2 ✓ sig.
Class B/2 (Secretin family receptors)
PTH, PTHLH
 Reactome 2 / 18 27.2× 2.39e-3 2.66e-2 ✓ sig.
Osteoclast differentiation
CALCR, TNF, TNFRSF11B, TNFSF11
 KEGG 4 / 142 6.9× 2.63e-3 2.85e-2 ✓ sig.
Adipocytokine signaling pathway
TNF, POMC, LEPR
 KEGG 3 / 70 10.5× 2.88e-3 3.04e-2 ✓ sig.
Steroid biosynthesis
CYP24A1, CYP27B1
 KEGG 2 / 20 24.5× 2.96e-3 3.09e-2 ✓ sig.
Neuroactive ligand-receptor interaction
CALCA, CALCR, PTH, POMC, LEPR, PTGER2
 KEGG 6 / 370 4.0× 3.75e-3 3.65e-2 ✓ sig.
Defective CYP24A1 causes Hypercalcemia, infantile (HCAI)
CYP24A1
 Reactome 1 / 1 245× 4.08e-3 3.88e-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 ⇵
calcium ion homeostasis
KL, TRPV5, CYP27B1, PTH, TNFSF11
 GO:0055074 5 / 42 45.4× 7.95e-8 1.01e-5 ✓ sig.
adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway
CASR, PTH, PTHLH
 GO:0140582 3 / 5 229× 1.69e-7 1.91e-5 ✓ sig.
adenylate cyclase-activating G protein-coupled receptor signaling pathway
CASR, ADCY10, CALCA, CALCR, PTH, PTHLH, PTGER2
 GO:0007189 7 / 161 16.6× 1.96e-7 2.17e-5 ✓ sig.
response to vitamin D
CYP24A1, KL, CYP27B1, PTH
 GO:0033280 4 / 21 72.6× 2.42e-7 2.58e-5 ✓ sig.
response to fibroblast growth factor
CASR, KL, PTH
 GO:0071774 3 / 11 104× 2.75e-6 1.90e-4 ✓ sig.
cilium organization
CFAP61, TTC29, CCDC146, ARMC2
 GO:0044782 4 / 40 38.1× 3.56e-6 2.33e-4 ✓ sig.
cellular response to vitamin D
CASR, CYP24A1, CYP27B1
 GO:0071305 3 / 13 88.0× 4.76e-6 2.93e-4 ✓ sig.
sperm flagellum assembly
CFAP61, DNHD1, CCDC146
 GO:0120316 3 / 20 57.2× 1.87e-5 8.64e-4 ✓ sig.
flagellated sperm motility
AKAP3, ARMC12, DNHD1, CCDC146, ARMC2
 GO:0030317 5 / 142 13.4× 3.44e-5 1.38e-3 ✓ sig.
amylin receptor 1 signaling pathway
CALCA, CALCR
 GO:0150059 2 / 4 191× 4.03e-5 1.56e-3 ✓ sig.
amylin receptor 2 signaling pathway
CALCA, CALCR
 GO:0150060 2 / 4 191× 4.03e-5 1.56e-3 ✓ sig.
cAMP metabolic process
PTH, PTHLH
 GO:0046058 2 / 4 191× 4.03e-5 1.56e-3 ✓ sig.
vitamin D catabolic process
CYP24A1, CYP27B1
 GO:0042369 2 / 4 191× 4.03e-5 1.56e-3 ✓ sig.
small molecule biosynthetic process
CYP24A1, CYP27B1
 GO:0044283 2 / 4 191× 4.03e-5 1.56e-3 ✓ sig.
monocyte chemotaxis
CALCA, IL6, TNFSF11
 GO:0002548 3 / 26 44.0× 4.22e-5 1.62e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hypercalcemia Hypercalciuria 0.211 4 3.84e-11 3.99e-10 ✓ sig.
Hypercalciuria Idiopathic infantile hypercalcemia 0.273 3 5.52e-10 5.14e-9 ✓ sig.
Hypercalcemia Idiopathic infantile hypercalcemia 0.200 3 1.88e-9 1.66e-8 ✓ sig.
Hypercalcemia Kidney and ureter calculus 0.200 3 1.88e-9 1.66e-8 ✓ sig.
Idiopathic infantile hypercalcemia Kidney and ureter calculus 0.286 2 3.04e-7 1.96e-6 ✓ sig.
Hypercalciuria Kidney and ureter calculus 0.167 2 1.82e-6 1.02e-5 ✓ sig.
Male infertility large polyploid spermatozoa Male infertility spermatogenesis disorder 0.083 2 3.63e-5 1.67e-4 ✓ sig.
Cerebral embolism Intracranial embolism 0.500 1 6.49e-5 2.32e-4 ✓ sig.
Cerebral embolism Idiopathic infantile hypercalcemia 0.200 1 2.60e-4 6.48e-4 ✓ sig.
Idiopathic infantile hypercalcemia Intracranial embolism 0.200 1 2.60e-4 6.48e-4 ✓ sig.
Cerebral embolism Infertility 0.111 1 5.20e-4 1.06e-3 ✓ sig.
Infertility Intracranial embolism 0.111 1 5.20e-4 1.06e-3 ✓ sig.
Infertility spermatogenic failure 5 0.111 1 5.20e-4 1.06e-3 ✓ sig.
Male infertility large polyploid spermatozoa spermatogenic failure 46 0.100 1 5.84e-4 1.15e-3 ✓ sig.
Male infertility large polyploid spermatozoa spermatogenic failure 5 0.100 1 5.84e-4 1.15e-3 ✓ sig.
Male infertility spermatogenesis disorder spermatogenic failure 39 0.059 1 1.04e-3 1.74e-3 ✓ sig.
Male infertility spermatogenesis disorder spermatogenic failure 5 0.059 1 1.04e-3 1.74e-3 ✓ sig.