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 171

9 diseases · 24 shared-gene connections
9 Diseases
9 Unique genes
0.280 Avg. similarity score
Paroxysmal extreme pain disorder Most-connected disease (8 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 ⇵
Paroxysmal extreme pain disorder 8 8 4
Congenital insensitivity to pain 7 7 6
Erythromelalgia 7 7 3
Congenital pain insensitivity 6 6 4
Chronic pain 5 5 1
Primary erythromelalgia 5 5 1
hereditary sensory and autonomic neuropathy type 7 5 5 1
Episodic pain syndrome 4 4 3
Metaphyseal enchondromatosis 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
SCN11A 6 / 9 Congenital insensitivity to pain, Congenital pain insensitivity, Episodic pain syndrome, Erythromelalgia and 2 more
SCN9A 6 / 9 Chronic pain, Congenital insensitivity to pain, Congenital pain insensitivity, Erythromelalgia and 2 more
SCN10A 4 / 9 Congenital insensitivity to pain, Episodic pain syndrome, Erythromelalgia, Paroxysmal extreme pain disorder
IDH1 2 / 9 Metaphyseal enchondromatosis, Paroxysmal extreme pain disorder
PRDM12 2 / 9 Congenital insensitivity to pain, Congenital pain insensitivity
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 ⇵
Phase 0 - rapid depolarisation
SCN9A, SCN10A, SCN11A
 Reactome 3 / 44 91.0× 3.80e-6 1.52e-4 ✓ sig.
Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate
IDH1
 Reactome 1 / 1 1,334× 7.49e-4 1.09e-2 ✓ sig.
NADPH regeneration
IDH1
 Reactome 1 / 1 1,334× 7.49e-4 1.09e-2 ✓ sig.
TRKA activation by NGF
NGF
 Reactome 1 / 2 667× 1.50e-3 1.85e-2 ✓ sig.
NFG and proNGF binds to p75NTR
NGF
 Reactome 1 / 2 667× 1.50e-3 1.85e-2 ✓ sig.
Inflammatory mediator regulation of TRP channels
NGF, TRPA1
 KEGG 2 / 99 27.0× 2.33e-3 2.55e-2 ✓ sig.
Axonal growth stimulation
NGF
 Reactome 1 / 4 334× 2.99e-3 3.07e-2 ✓ sig.
NGF processing
NGF
 Reactome 1 / 4 334× 2.99e-3 3.07e-2 ✓ sig.
ARMS-mediated activation
NGF
 Reactome 1 / 5 267× 3.74e-3 3.59e-2 ✓ sig.
NADE modulates death signalling
NGF
 Reactome 1 / 6 222× 4.49e-3 4.08e-2 ✓ sig.
PI3K/AKT activation
NGF
 Reactome 1 / 9 148× 6.73e-3 5.32e-2
Retrograde neurotrophin signalling
NGF
 Reactome 1 / 11 121× 8.22e-3 6.07e-2
Formation of annular gap junctions
CLTCL1
 Reactome 1 / 11 121× 8.22e-3 6.07e-2
Frs2-mediated activation
NGF
 Reactome 1 / 12 111× 8.96e-3 6.42e-2
Gap junction degradation
CLTCL1
 Reactome 1 / 12 111× 8.96e-3 6.42e-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 ⇵
sensory perception of pain
SCN9A, SCN11A, PRDM12, NGF, TRPA1
 GO:0019233 5 / 44 236× 7.16e-12 2.71e-9 ✓ sig.
detection of mechanical stimulus involved in sensory perception
SCN9A, SCN11A, TRPA1
 GO:0050974 3 / 8 779× 4.32e-9 8.18e-7 ✓ sig.
detection of temperature stimulus involved in sensory perception of pain
SCN9A, SCN11A, PRDM12
 GO:0050965 3 / 20 311× 8.77e-8 1.08e-5 ✓ sig.
cardiac muscle cell action potential involved in contraction
SCN9A, SCN10A, SCN11A
 GO:0086002 3 / 24 260× 1.56e-7 1.75e-5 ✓ sig.
circadian rhythm
SCN9A, SCN11A, NGF
 GO:0007623 3 / 82 76.0× 6.71e-6 3.79e-4 ✓ sig.
membrane depolarization during action potential
SCN10A, SCN11A
 GO:0086010 2 / 10 415× 9.26e-6 4.92e-4 ✓ sig.
detection of mechanical stimulus involved in sensory perception of pain
SCN11A, TRPA1
 GO:0050966 2 / 14 297× 1.87e-5 8.50e-4 ✓ sig.
cellular response to cold
SCN11A, TRPA1
 GO:0070417 2 / 15 277× 2.16e-5 9.54e-4 ✓ sig.
monoatomic ion transmembrane transport
SCN9A, SCN10A, SCN11A, TRPA1
 GO:0034220 4 / 404 20.6× 2.49e-5 1.06e-3 ✓ sig.
sodium ion transmembrane transport
SCN9A, SCN10A, SCN11A
 GO:0035725 3 / 134 46.5× 2.93e-5 1.20e-3 ✓ sig.
behavioral response to pain
SCN9A, SCN11A
 GO:0048266 2 / 18 231× 3.14e-5 1.27e-3 ✓ sig.
response to pain
SCN11A, TRPA1
 GO:0048265 2 / 19 219× 3.51e-5 1.38e-3 ✓ sig.
sodium ion transport
SCN9A, SCN10A, SCN11A
 GO:0006814 3 / 144 43.3× 3.64e-5 1.42e-3 ✓ sig.
transmembrane transport
SCN9A, SCN10A, SCN11A, TRPA1
 GO:0055085 4 / 557 14.9× 8.73e-5 2.74e-3 ✓ sig.
response to cold
SCN11A, TRPA1
 GO:0009409 2 / 31 134× 9.52e-5 2.91e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Erythromelalgia Paroxysmal extreme pain disorder 0.600 3 6.58e-12 7.74e-11 ✓ sig.
Congenital insensitivity to pain Erythromelalgia 0.429 3 3.29e-11 3.62e-10 ✓ sig.
Congenital insensitivity to pain Paroxysmal extreme pain disorder 0.375 3 1.31e-10 1.37e-9 ✓ sig.
Congenital insensitivity to pain Congenital pain insensitivity 0.375 3 1.31e-10 1.37e-9 ✓ sig.
Episodic pain syndrome Erythromelalgia 0.400 2 7.59e-8 5.72e-7 ✓ sig.
Congenital pain insensitivity Erythromelalgia 0.333 2 1.52e-7 1.09e-6 ✓ sig.
Episodic pain syndrome Paroxysmal extreme pain disorder 0.333 2 1.52e-7 1.09e-6 ✓ sig.
Congenital pain insensitivity Paroxysmal extreme pain disorder 0.286 2 3.04e-7 2.06e-6 ✓ sig.
Congenital insensitivity to pain Episodic pain syndrome 0.250 2 3.80e-7 2.53e-6 ✓ sig.
Chronic pain Primary erythromelalgia 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Chronic pain Erythromelalgia 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Erythromelalgia Primary erythromelalgia 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Episodic pain syndrome hereditary sensory and autonomic neuropathy type 7 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Erythromelalgia hereditary sensory and autonomic neuropathy type 7 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Chronic pain Paroxysmal extreme pain disorder 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Congenital pain insensitivity hereditary sensory and autonomic neuropathy type 7 0.200 1 2.60e-4 6.40e-4 ✓ sig.
hereditary sensory and autonomic neuropathy type 7 Paroxysmal extreme pain disorder 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Metaphyseal enchondromatosis Paroxysmal extreme pain disorder 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Chronic pain Congenital pain insensitivity 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Congenital pain insensitivity Primary erythromelalgia 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Paroxysmal extreme pain disorder Primary erythromelalgia 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Congenital insensitivity to pain hereditary sensory and autonomic neuropathy type 7 0.143 1 3.90e-4 8.52e-4 ✓ sig.
Chronic pain Congenital insensitivity to pain 0.143 1 3.90e-4 8.52e-4 ✓ sig.
Congenital insensitivity to pain Primary erythromelalgia 0.143 1 3.90e-4 8.52e-4 ✓ sig.