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 579

5 diseases · 7 shared-gene connections
5 Diseases
34 Unique genes
0.227 Avg. similarity score
Congenital cerebellar ataxia 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 ⇵
Congenital cerebellar ataxia 4 4 2
Chondromyxoid fibroma 3 3 1
Spinocerebellar ataxia, autosomal recessive 13 3 3 1
Temporal lobe epilepsy 3 3 33
Autosomal recessive spinocerebellar ataxia 18 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
GRM1 4 / 5 Chondromyxoid fibroma, Congenital cerebellar ataxia, Spinocerebellar ataxia, autosomal recessive 13, Temporal lobe epilepsy
GRID2 2 / 5 Autosomal recessive spinocerebellar ataxia 18, Congenital cerebellar ataxia
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 ⇵
Neuroactive ligand-receptor interaction
GRID2, GRM1, BDKRB1, BDKRB2, CNR1, GRM2, GRM3, GRM4, GRM5, NPY, NPY2R, P2RX4
 KEGG 16 / 370 15.3× 6.35e-16 2.30e-13 ✓ sig.
G alpha (i) signalling events
BDKRB1, BDKRB2, CNR1, GRM2, GRM3, GRM4, NPY, NPY2R, PDYN, GAL
 Reactome 10 / 249 14.2× 1.04e-9 9.62e-8 ✓ sig.
Class C/3 (Metabotropic glutamate/pheromone receptors)
GRM1, GRM2, GRM3, GRM4, GRM5
 Reactome 5 / 38 46.5× 6.28e-8 3.73e-6 ✓ sig.
Calcium signaling pathway
GRM1, BDKRB1, BDKRB2, GRM5, KDR, P2RX4, P2RX7, VEGFA
 KEGG 8 / 254 11.1× 4.04e-7 1.90e-5 ✓ sig.
Peptide ligand-binding receptors
BDKRB1, BDKRB2, NPY, NPY2R, PDYN, GAL
 Reactome 6 / 106 20.0× 4.51e-7 2.09e-5 ✓ sig.
Glutamatergic synapse
GRM1, GRM2, GRM3, GRM4, GRM5, SLC1A1
 KEGG 6 / 116 18.3× 7.69e-7 3.31e-5 ✓ sig.
Phospholipase D signaling pathway
GRM1, GRM2, GRM3, GRM4, GRM5
 KEGG 5 / 149 11.9× 5.72e-5 1.21e-3 ✓ sig.
Cation-coupled Chloride cotransporters
SLC12A2, SLC12A5
 Reactome 2 / 7 101× 1.62e-4 2.78e-3 ✓ sig.
VEGF binds to VEGFR leading to receptor dimerization
KDR, VEGFA
 Reactome 2 / 8 88.3× 2.16e-4 3.48e-3 ✓ sig.
Platelet homeostasis
P2RX4, P2RX7
 Reactome 2 / 8 88.3× 2.16e-4 3.48e-3 ✓ sig.
Cocaine addiction
GRM2, GRM3, PDYN
 KEGG 3 / 49 21.6× 3.49e-4 5.06e-3 ✓ sig.
Elevation of cytosolic Ca2+ levels
P2RX4, P2RX7
 Reactome 2 / 13 54.3× 5.95e-4 7.64e-3 ✓ sig.
VEGFR2 mediated cell proliferation
KDR, VEGFA
 Reactome 2 / 14 50.5× 6.93e-4 8.58e-3 ✓ sig.
G alpha (q) signalling events
GRM1, BDKRB1, BDKRB2, GRM5
 Reactome 4 / 172 8.2× 1.35e-3 1.42e-2 ✓ sig.
Purinergic signaling in leishmaniasis infection
P2RX4, P2RX7
 Reactome 2 / 24 29.4× 2.06e-3 1.95e-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 ⇵
adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway
GRM1, GRM2, GRM3, GRM4, GRM5
 GO:0007196 5 / 9 305× 1.84e-12 8.35e-10 ✓ sig.
chemical synaptic transmission
GRM1, GRM2, GRM3, GRM4, GRM5, KCNC4, NPY, PDYN, SLC12A5, SLC1A1
 GO:0007268 10 / 236 23.3× 8.58e-12 3.32e-9 ✓ sig.
G protein-coupled glutamate receptor signaling pathway
GRM1, GRM2, GRM3, GRM4, GRM5
 GO:0007216 5 / 14 196× 2.90e-11 9.98e-9 ✓ sig.
synaptic signaling via neuropeptide
GRID2, GRM1, NPY, NPY2R
 GO:0099538 4 / 9 244× 1.14e-9 2.60e-7 ✓ sig.
regulation of synaptic transmission, glutamatergic
GRM1, GRM2, GRM3, GRM4, GRM5
 GO:0051966 5 / 33 83.3× 3.36e-9 6.74e-7 ✓ sig.
positive regulation of MAPK cascade
GRM1, GRM4, GRM5, KDR, P2RX7, TEK, VEGFA
 GO:0043410 7 / 224 17.2× 1.32e-7 1.61e-5 ✓ sig.
monoatomic ion transport
GRID2, KCNAB1, KCNC4, NALCN, P2RX4, P2RX7, SLC12A2, SLC12A5, SLC1A1, TRPV1
 GO:0006811 10 / 667 8.2× 1.89e-7 2.16e-5 ✓ sig.
locomotory behavior
GRM1, GRM5, NPY2R, SLC1A1, RELN
 GO:0007626 5 / 99 27.8× 9.28e-7 8.10e-5 ✓ sig.
sensory perception of pain
GRM1, P2RX4, P2RX7, TRPV1
 GO:0019233 4 / 44 50.0× 1.18e-6 9.82e-5 ✓ sig.
positive regulation of endothelial cell chemotaxis
KDR, P2RX4, VEGFA
 GO:2001028 3 / 13 127× 1.55e-6 1.24e-4 ✓ sig.
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
GRM2, KDR, P2RX4, TEK, VEGFA, RELN
 GO:0051897 6 / 217 15.2× 2.35e-6 1.73e-4 ✓ sig.
cellular response to ATP
P2RX4, P2RX7, TRPV1
 GO:0071318 3 / 19 86.8× 5.23e-6 3.28e-4 ✓ sig.
glutamate receptor signaling pathway
GRID2, GRM2, SLC1A1
 GO:0007215 3 / 19 86.8× 5.23e-6 3.28e-4 ✓ sig.
monoatomic ion transmembrane transport
GRID2, ANO4, KCNC4, NALCN, P2RX4, P2RX7, TRPV1
 GO:0034220 7 / 404 9.5× 6.81e-6 4.03e-4 ✓ sig.
potassium ion transmembrane transport
KCNAB1, KCNC4, NALCN, P2RX7, SLC12A5
 GO:0071805 5 / 150 18.3× 7.19e-6 4.21e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Chondromyxoid fibroma Spinocerebellar ataxia, autosomal recessive 13 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Autosomal recessive spinocerebellar ataxia 18 Congenital cerebellar ataxia 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Chondromyxoid fibroma Congenital cerebellar ataxia 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Congenital cerebellar ataxia Spinocerebellar ataxia, autosomal recessive 13 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Chondromyxoid fibroma Temporal lobe epilepsy 0.029 1 2.13e-3 2.85e-3 ✓ sig.
Spinocerebellar ataxia, autosomal recessive 13 Temporal lobe epilepsy 0.029 1 2.13e-3 2.85e-3 ✓ sig.
Congenital cerebellar ataxia Temporal lobe epilepsy 0.029 1 4.26e-3 5.20e-3 ✓ sig.