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 582

5 diseases · 7 shared-gene connections
5 Diseases
22 Unique genes
0.372 Avg. similarity score
Basal ganglia disease Most-connected disease (4 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 ⇵
Basal ganglia disease 4 4 14
Fahr's disease 3 3 7
Idiopathic basal ganglia calcification 3 3 12
Primary familial brain calcification 3 3 8
Myopathy with extrapyramidal signs 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
PDGFB 4 / 5 Basal ganglia disease, Fahr's disease, Idiopathic basal ganglia calcification, Primary familial brain calcification
PDGFRB 4 / 5 Basal ganglia disease, Fahr's disease, Idiopathic basal ganglia calcification, Primary familial brain calcification
SLC20A2 4 / 5 Basal ganglia disease, Fahr's disease, Idiopathic basal ganglia calcification, Primary familial brain calcification
XPR1 4 / 5 Basal ganglia disease, Fahr's disease, Idiopathic basal ganglia calcification, Primary familial brain calcification
JAM2 3 / 5 Fahr's disease, Idiopathic basal ganglia calcification, Primary familial brain calcification
MYORG 3 / 5 Fahr's disease, Idiopathic basal ganglia calcification, Primary familial brain calcification
NAA60 3 / 5 Fahr's disease, Idiopathic basal ganglia calcification, Primary familial brain calcification
CMPK2 2 / 5 Idiopathic basal ganglia calcification, Primary familial brain calcification
MICU1 2 / 5 Basal ganglia disease, Myopathy with extrapyramidal signs
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 ⇵
Gap junction
PDGFB, PDGFRB, DRD2, HTR2A
 KEGG 4 / 89 24.5× 1.86e-5 4.91e-4 ✓ sig.
Dopamine receptors
DRD2, DRD3
 Reactome 2 / 5 218× 3.19e-5 7.64e-4 ✓ sig.
DDX58/IFIH1-mediated induction of interferon-alpha/beta
IFIH1, ISG15
 Reactome 2 / 17 64.2× 4.28e-4 5.93e-3 ✓ sig.
Negative regulators of DDX58/IFIH1 signaling
IFIH1, ISG15
 Reactome 2 / 27 40.4× 1.09e-3 1.21e-2 ✓ sig.
Downstream signal transduction
PDGFB, PDGFRB
 Reactome 2 / 29 37.6× 1.26e-3 1.35e-2 ✓ sig.
Signaling by PDGF
PDGFB, PDGFRB
 Reactome 2 / 33 33.1× 1.63e-3 1.64e-2 ✓ sig.
Defective SLC20A2 causes idiopathic basal ganglia calcification 1 (IBGC1)
SLC20A2
 Reactome 1 / 1 546× 1.83e-3 1.78e-2 ✓ sig.
JAK-STAT signaling pathway
PDGFB, PDGFRB, PRL
 KEGG 3 / 168 9.7× 3.41e-3 2.79e-2 ✓ sig.
Sodium-coupled phosphate cotransporters
SLC20A2
 Reactome 1 / 2 273× 3.66e-3 2.93e-2 ✓ sig.
Neuroactive ligand-receptor interaction
DRD2, DRD3, HTR2A, PRL
 KEGG 4 / 370 5.9× 4.18e-3 3.22e-2 ✓ sig.
Rap1 signaling pathway
PDGFB, PDGFRB, DRD2
 KEGG 3 / 211 7.8× 6.43e-3 4.30e-2 ✓ sig.
Hormone signaling
DRD2, DRD3, PRL
 KEGG 3 / 219 7.5× 7.13e-3 4.60e-2 ✓ sig.
RIG-I-like receptor signaling pathway
IFIH1, ISG15
 KEGG 2 / 72 15.2× 7.58e-3 4.78e-2 ✓ sig.
Melanoma
PDGFB, PDGFRB
 KEGG 2 / 73 15.0× 7.78e-3 4.87e-2 ✓ sig.
Constitutive Signaling by Aberrant PI3K in Cancer
PDGFB, PDGFRB
 Reactome 2 / 75 14.6× 8.20e-3 5.04e-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 ⇵
negative regulation of synaptic transmission, glutamatergic
DRD2, DRD3, HTR2A
 GO:0051967 3 / 10 255× 1.69e-7 1.97e-5 ✓ sig.
positive regulation of DNA biosynthetic process
PDGFB, PDGFRB, HTR2A
 GO:2000573 3 / 12 212× 3.09e-7 3.27e-5 ✓ sig.
regulation of dopamine secretion
DRD2, DRD3, HTR2A
 GO:0014059 3 / 15 170× 6.38e-7 5.96e-5 ✓ sig.
behavioral response to cocaine
DRD2, DRD3, HTR2A
 GO:0048148 3 / 17 150× 9.53e-7 8.27e-5 ✓ sig.
regulation of amine transport
DRD2, DRD3
 GO:0051952 2 / 2 849× 1.32e-6 1.08e-4 ✓ sig.
positive regulation of ERK1 and ERK2 cascade
PDGFB, PDGFRB, DRD2, HTR2A, PDE8B
 GO:0070374 5 / 201 21.1× 3.11e-6 2.16e-4 ✓ sig.
positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway
PDGFB, PDGFRB
 GO:0035793 2 / 3 566× 3.97e-6 2.63e-4 ✓ sig.
acid secretion
DRD2, DRD3
 GO:0046717 2 / 3 566× 3.97e-6 2.63e-4 ✓ sig.
positive regulation of mitotic nuclear division
PDGFB, PDGFRB, DRD3
 GO:0045840 3 / 29 87.9× 5.07e-6 3.21e-4 ✓ sig.
smooth muscle adaptation
PDGFB, PDGFRB
 GO:0014805 2 / 4 425× 7.93e-6 4.55e-4 ✓ sig.
regulation of secretion by cell
DRD2, DRD3
 GO:1903530 2 / 4 425× 7.93e-6 4.55e-4 ✓ sig.
response to histamine
DRD2, DRD3
 GO:0034776 2 / 4 425× 7.93e-6 4.55e-4 ✓ sig.
response to cocaine
DRD2, DRD3, HTR2A
 GO:0042220 3 / 35 72.8× 9.05e-6 5.03e-4 ✓ sig.
regulation of dopamine uptake involved in synaptic transmission
DRD2, DRD3
 GO:0051584 2 / 5 340× 1.32e-5 6.74e-4 ✓ sig.
adenylate cyclase-inhibiting dopamine receptor signaling pathway
DRD2, DRD3
 GO:0007195 2 / 5 340× 1.32e-5 6.74e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Idiopathic basal ganglia calcification Primary familial brain calcification 0.615 8 6.04e-27 1.10e-25 ✓ sig.
Fahr's disease Primary familial brain calcification 0.778 7 1.89e-25 3.27e-24 ✓ sig.
Fahr's disease Idiopathic basal ganglia calcification 0.538 7 1.87e-23 3.05e-22 ✓ sig.
Basal ganglia disease Fahr's disease 0.222 4 1.46e-11 1.46e-10 ✓ sig.
Basal ganglia disease Primary familial brain calcification 0.211 4 2.92e-11 2.86e-10 ✓ sig.
Basal ganglia disease Idiopathic basal ganglia calcification 0.174 4 2.06e-10 1.88e-9 ✓ sig.
Basal ganglia disease Myopathy with extrapyramidal signs 0.067 1 9.04e-4 1.41e-3 ✓ sig.