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 196

8 diseases · 15 shared-gene connections
8 Diseases
68 Unique genes
0.199 Avg. similarity score
ATP1A3-associated neurological disorder Most-connected disease (5 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 ⇵
ATP1A3-associated neurological disorder 5 5 1
Capos syndrome 5 5 1
Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss 5 5 1
Congenital epicanthus 5 5 14
Anhedonia 4 4 26
Alternating hemiplegia of childhood 3 3 2
Esophageal atresia 2 2 32
fibrodysplasia ossificans progressiva 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
ATP1A3 7 / 8 Alternating hemiplegia of childhood, Anhedonia, ATP1A3-associated neurological disorder, Capos syndrome and 3 more
ACVR1 2 / 8 Congenital epicanthus, fibrodysplasia ossificans progressiva
CACNA1C 2 / 8 Anhedonia, Esophageal atresia
KCNA6 2 / 8 Congenital epicanthus, Esophageal atresia
TCF4 2 / 8 Congenital epicanthus, Esophageal atresia
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 ⇵
cAMP signaling pathway
ATP1A2, ATP1A3, CACNA1C, CRH, CRHR1, CRHR2, DRD2, HTR1A, KCNK2, MAPK1, PDE4D
 KEGG 11 / 226 8.6× 4.91e-8 3.51e-6 ✓ sig.
Hormone signaling
CRH, CRHR1, CRHR2, DRD2, MC4R, OPRK1, ACVR1, INSR, STAT5A
 KEGG 9 / 219 7.3× 3.67e-6 1.47e-4 ✓ sig.
Aldosterone-regulated sodium reabsorption
ATP1A2, ATP1A3, MAPK1, INSR
 KEGG 4 / 38 18.6× 6.00e-5 1.48e-3 ✓ sig.
Synaptic vesicle cycle
SLC17A7, SLC1A3, SLC6A3, SLC6A4, ATP6V0A1
 KEGG 5 / 79 11.2× 8.17e-5 1.90e-3 ✓ sig.
Class B/2 (Secretin family receptors)
CRH, CRHR1, CRHR2
 Reactome 3 / 18 29.4× 1.33e-4 2.83e-3 ✓ sig.
G alpha (s) signalling events
CRH, CRHR1, CRHR2, MC4R, ARRB1, PDE4D
 Reactome 6 / 140 7.6× 1.36e-4 2.88e-3 ✓ sig.
Adrenergic signaling in cardiomyocytes
ATP1A2, ATP1A3, CACNA1C, KCNK2, MAPK1, MYH7
 KEGG 6 / 154 6.9× 2.29e-4 4.36e-3 ✓ sig.
Cushing syndrome
CACNA1C, CRH, CRHR1, CRHR2, KCNK2, MAPK1
 KEGG 6 / 155 6.8× 2.37e-4 4.47e-3 ✓ sig.
cGMP-PKG signaling pathway
ATP1A2, ATP1A3, CACNA1C, MAPK1, MYH7, INSR
 KEGG 6 / 166 6.4× 3.43e-4 5.96e-3 ✓ sig.
GnRH secretion
CACNA1C, MAPK1, ARRB1, KCNN3
 KEGG 4 / 65 10.9× 4.91e-4 7.86e-3 ✓ sig.
Thyroid hormone signaling pathway
ATP1A2, ATP1A3, MAPK1, MYH7, NOTCH1
 KEGG 5 / 122 7.2× 6.23e-4 9.48e-3 ✓ sig.
Dopaminergic synapse
CACNA1C, COMT, DRD2, SLC6A3, ARRB1
 KEGG 5 / 132 6.7× 8.90e-4 1.24e-2 ✓ sig.
Proteoglycans in cancer
ANK3, MAPK1, PTK2, PTPN11, DROSHA, ITGB1
 KEGG 6 / 204 5.2× 1.02e-3 1.37e-2 ✓ sig.
Neuroactive ligand-receptor interaction
CRH, CRHR1, CRHR2, DRD2, HTR1A, MC4R, OPRK1, GABRG2
 KEGG 8 / 370 3.8× 1.11e-3 1.46e-2 ✓ sig.
MAPK1 (ERK2) activation
MAPK1, PTPN11
 Reactome 2 / 9 39.2× 1.11e-3 1.46e-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 ⇵
response to cocaine
CRH, DRD2, OPRK1, PITX3, SLC6A3, EFTUD2
 GO:0042220 6 / 35 47.1× 2.77e-9 5.50e-7 ✓ sig.
potassium ion transmembrane transport
ATP1A2, KCNK2, SLC17A7, SLC1A3, ABCC9, KCNA6, KCNQ2, KCNN3
 GO:0071805 8 / 150 14.7× 7.03e-8 9.00e-6 ✓ sig.
cell communication by electrical coupling involved in cardiac conduction
ATP1A2, ATP1A3, CACNA1C, GJA1
 GO:0086064 4 / 12 91.6× 7.76e-8 9.73e-6 ✓ sig.
potassium ion transport
ATP1A2, ATP1A3, KCNK2, SLC17A7, ABCC9, KCNA6, KCNQ2, KCNN3
 GO:0006813 8 / 152 14.5× 7.79e-8 9.76e-6 ✓ sig.
response to nicotine
ATP1A2, DRD2, MAPK1, OPRK1, SLC6A3
 GO:0035094 5 / 40 34.4× 3.28e-7 3.28e-5 ✓ sig.
chemical synaptic transmission
CRH, HTR1A, MAPK1, OPRK1, SLC17A7, SLC1A3, KCNQ2, GABRG2
 GO:0007268 8 / 236 9.3× 2.21e-6 1.56e-4 ✓ sig.
fear response
ATP1A2, COMT, CRHR1
 GO:0042596 3 / 8 103× 2.55e-6 1.74e-4 ✓ sig.
positive regulation of neuroblast proliferation
DISC1, DRD2, ITGB1, NOTCH1
 GO:0002052 4 / 29 37.9× 3.56e-6 2.29e-4 ✓ sig.
heart development
CACNA1C, GJA1, MAPK1, ABCC9, ACVR1, PTPN11, NOTCH1, TERT
 GO:0007507 8 / 273 8.1× 6.49e-6 3.69e-4 ✓ sig.
neurotransmitter uptake
ATP1A2, SLC1A3, SLC6A3
 GO:0001504 3 / 11 74.9× 7.45e-6 4.13e-4 ✓ sig.
cellular response to cocaine
COMT, CRH, SLC1A3
 GO:0071314 3 / 11 74.9× 7.45e-6 4.13e-4 ✓ sig.
regulation of serotonin secretion
CRH, HTR1A
 GO:0014062 2 / 2 275× 1.30e-5 6.43e-4 ✓ sig.
memory
COMT, KCNK2, SLC6A4, INSR, PLK2
 GO:0007613 5 / 87 15.8× 1.61e-5 7.60e-4 ✓ sig.
positive regulation of intracellular signal transduction
ARRB1, ACVR1, PTPN11, MID2
 GO:1902533 4 / 43 25.6× 1.78e-5 8.18e-4 ✓ sig.
regulation of ossification
MAPK1, ACVR1, TENT5A
 GO:0030278 3 / 15 55.0× 2.03e-5 9.09e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Congenital epicanthus Esophageal atresia 0.068 3 2.92e-6 1.67e-5 ✓ sig.
ATP1A3-associated neurological disorder Capos syndrome 0.500 1 6.49e-5 2.34e-4 ✓ sig.
ATP1A3-associated neurological disorder Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Capos syndrome Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Alternating hemiplegia of childhood Capos syndrome 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Alternating hemiplegia of childhood Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Alternating hemiplegia of childhood ATP1A3-associated neurological disorder 0.333 1 1.30e-4 3.90e-4 ✓ sig.
ATP1A3-associated neurological disorder Congenital epicanthus 0.067 1 9.09e-4 1.56e-3 ✓ sig.
Capos syndrome Congenital epicanthus 0.067 1 9.09e-4 1.56e-3 ✓ sig.
Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss Congenital epicanthus 0.067 1 9.09e-4 1.56e-3 ✓ sig.
Congenital epicanthus fibrodysplasia ossificans progressiva 0.067 1 9.09e-4 1.56e-3 ✓ sig.
Anhedonia Esophageal atresia 0.035 2 1.32e-3 2.07e-3 ✓ sig.
Anhedonia ATP1A3-associated neurological disorder 0.037 1 1.69e-3 2.51e-3 ✓ sig.
Anhedonia Capos syndrome 0.037 1 1.69e-3 2.51e-3 ✓ sig.
Anhedonia Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss 0.037 1 1.69e-3 2.51e-3 ✓ sig.