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 61

15 diseases · 38 shared-gene connections
15 Diseases
18 Unique genes
0.295 Avg. similarity score
Dilated cardiomyopathy 1E Most-connected disease (10 links)
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Disease Searched: Heart block, progressive, type ia 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 ⇵
Dilated cardiomyopathy 1E 10 10 1
Heart block, nonprogressive 10 10 1
Heart block, progressive, type ia 10 10 1
Progressive familial heart block 1a 9 9 1
Ectopic rhythm 6 6 2
Atrial standstill 5 5 3
Cardiac rhythm disease 5 5 2
Paroxysmal tachycardia 5 5 7
Paroxysmal ventricular fibrillation 4 4 2
Sudden infant death syndrome 4 4 4
Torsades de pointes 4 4 3
Hypercapnia 1 1 2
Intellectual developmental disorder, autosomal dominant 33 1 1 1
Neurodevelopmental disorder with cerebellar ataxia and movement disorders 1 1 1
Primary ciliary dyskinesia 5 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
SCN5A 11 / 15 Atrial standstill, Cardiac rhythm disease, Dilated cardiomyopathy 1E, Ectopic rhythm and 7 more
DPP6 2 / 15 Intellectual developmental disorder, autosomal dominant 33, Paroxysmal ventricular fibrillation
HYDIN 2 / 15 Paroxysmal tachycardia, Primary ciliary dyskinesia 5
KCND3 2 / 15 Ectopic rhythm, Neurodevelopmental disorder with cerebellar ataxia and movement disorders
NPPA 2 / 15 Atrial standstill, Hypercapnia
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 ⇵
Voltage gated Potassium channels
KCND3, KCNH2
 Reactome 2 / 43 31.0× 1.85e-3 1.79e-2 ✓ sig.
Opioid Signalling
PDYN
 Reactome 1 / 3 222× 4.49e-3 3.39e-2 ✓ sig.
Viral myocarditis
CAV1, CAV3
 KEGG 2 / 70 19.1× 4.82e-3 3.57e-2 ✓ sig.
Bacterial invasion of epithelial cells
CAV1, CAV3
 KEGG 2 / 78 17.1× 5.96e-3 4.10e-2 ✓ sig.
ATP sensitive Potassium channels
KCNJ8
 Reactome 1 / 4 167× 5.98e-3 4.10e-2 ✓ sig.
CREB3 factors activate genes
CREBRF
 Reactome 1 / 5 133× 7.47e-3 4.73e-2 ✓ sig.
NOSTRIN mediated eNOS trafficking
CAV1
 Reactome 1 / 5 133× 7.47e-3 4.73e-2 ✓ sig.
Biosynthesis of maresin-like SPMs
CYP3A4
 Reactome 1 / 6 111× 8.96e-3 5.31e-2
Phase 1 - inactivation of fast Na+ channels
KCND3
 Reactome 1 / 7 95.3× 1.04e-2 5.84e-2
Phase 3 - rapid repolarisation
KCNH2
 Reactome 1 / 8 83.4× 1.19e-2 6.32e-2
FOXO-mediated transcription of cell cycle genes
CAV1
 Reactome 1 / 11 60.7× 1.64e-2 7.63e-2
Physiological factors
NPPA
 Reactome 1 / 12 55.6× 1.78e-2 8.03e-2
Fluid shear stress and atherosclerosis
CAV1, CAV3
 KEGG 2 / 141 9.5× 1.85e-2 8.21e-2
Spinocerebellar ataxia
KCND3, PDYN
 KEGG 2 / 144 9.3× 1.93e-2 8.38e-2
eNOS activation
CAV1
 Reactome 1 / 13 51.3× 1.93e-2 8.40e-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 ⇵
regulation of heart rate by cardiac conduction
GJA5, SCN5A, KCND3, CAV1, KCNH2
 GO:0086091 5 / 43 121× 4.25e-10 1.11e-7 ✓ sig.
ventricular cardiac muscle cell action potential
GJA5, SCN5A, KCNH2, CAV3
 GO:0086005 4 / 17 244× 1.42e-9 3.17e-7 ✓ sig.
regulation of ventricular cardiac muscle cell membrane repolarization
GJA5, SCN5A, KCNH2, CAV3
 GO:0060307 4 / 21 198× 3.57e-9 7.11e-7 ✓ sig.
regulation of ventricular cardiac muscle cell membrane depolarization
GJA5, SCN5A, CAV3
 GO:0060373 3 / 7 445× 2.62e-8 4.09e-6 ✓ sig.
negative regulation of potassium ion transmembrane transport
CAV1, KCNH2, CAV3
 GO:1901380 3 / 13 240× 2.13e-7 2.38e-5 ✓ sig.
membrane repolarization during ventricular cardiac muscle cell action potential
KCND3, KCNH2, KCNJ8
 GO:0098915 3 / 13 240× 2.13e-7 2.38e-5 ✓ sig.
cardiac conduction system development
GJA5, NPPA, SCN5A
 GO:0003161 3 / 16 195× 4.17e-7 4.18e-5 ✓ sig.
regulation of cardiac muscle contraction
GJA5, SCN5A, CAV3
 GO:0055117 3 / 24 130× 1.50e-6 1.20e-4 ✓ sig.
AV node cell to bundle of His cell communication
GJA5, SCN5A
 GO:0086067 2 / 3 692× 2.63e-6 1.89e-4 ✓ sig.
regulation of membrane depolarization during cardiac muscle cell action potential
GJA5, CAV3
 GO:1900825 2 / 4 519× 5.25e-6 3.29e-4 ✓ sig.
regulation of heart rate
SCN5A, KCNJ8, CAV3
 GO:0002027 3 / 39 79.9× 6.71e-6 3.99e-4 ✓ sig.
potassium ion transport
GJA5, KCND3, KCNH2, KCNJ8
 GO:0006813 4 / 152 27.3× 1.18e-5 6.16e-4 ✓ sig.
regulation of atrial cardiac muscle cell membrane repolarization
NPPA, SCN5A
 GO:0060372 2 / 6 346× 1.31e-5 6.71e-4 ✓ sig.
SA node cell action potential
GJA5, SCN5A
 GO:0086015 2 / 6 346× 1.31e-5 6.71e-4 ✓ sig.
vasodilation
GJA5, NPPA, KCNJ8
 GO:0042311 3 / 50 62.3× 1.43e-5 7.18e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Heart block, progressive, type ia Progressive familial heart block 1a 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Heart block, nonprogressive Progressive familial heart block 1a 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Heart block, nonprogressive Heart block, progressive, type ia 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Dilated cardiomyopathy 1E Heart block, nonprogressive 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Dilated cardiomyopathy 1E Heart block, progressive, type ia 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Dilated cardiomyopathy 1E Progressive familial heart block 1a 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Dilated cardiomyopathy 1E Paroxysmal ventricular fibrillation 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Heart block, nonprogressive Paroxysmal ventricular fibrillation 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Intellectual developmental disorder, autosomal dominant 33 Paroxysmal ventricular fibrillation 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Ectopic rhythm Neurodevelopmental disorder with cerebellar ataxia and movement disorders 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Ectopic rhythm Progressive familial heart block 1a 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Ectopic rhythm Heart block, progressive, type ia 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Ectopic rhythm Heart block, nonprogressive 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Dilated cardiomyopathy 1E Ectopic rhythm 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Heart block, progressive, type ia Paroxysmal ventricular fibrillation 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Cardiac rhythm disease Progressive familial heart block 1a 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Cardiac rhythm disease Heart block, progressive, type ia 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Cardiac rhythm disease Heart block, nonprogressive 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Cardiac rhythm disease Dilated cardiomyopathy 1E 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Dilated cardiomyopathy 1E Torsades de pointes 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Heart block, nonprogressive Torsades de pointes 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Heart block, progressive, type ia Torsades de pointes 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Atrial standstill Dilated cardiomyopathy 1E 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Progressive familial heart block 1a Torsades de pointes 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Atrial standstill Progressive familial heart block 1a 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Atrial standstill Heart block, progressive, type ia 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Atrial standstill Heart block, nonprogressive 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Cardiac rhythm disease Ectopic rhythm 0.250 1 2.58e-4 5.38e-4 ✓ sig.
Dilated cardiomyopathy 1E Sudden infant death syndrome 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Heart block, nonprogressive Sudden infant death syndrome 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Heart block, progressive, type ia Sudden infant death syndrome 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Progressive familial heart block 1a Sudden infant death syndrome 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Atrial standstill Hypercapnia 0.200 1 3.87e-4 7.33e-4 ✓ sig.
Heart block, nonprogressive Paroxysmal tachycardia 0.125 1 4.52e-4 8.26e-4 ✓ sig.
Heart block, progressive, type ia Paroxysmal tachycardia 0.125 1 4.52e-4 8.26e-4 ✓ sig.
Paroxysmal tachycardia Progressive familial heart block 1a 0.125 1 4.52e-4 8.26e-4 ✓ sig.
Dilated cardiomyopathy 1E Paroxysmal tachycardia 0.125 1 4.52e-4 8.26e-4 ✓ sig.
Paroxysmal tachycardia Primary ciliary dyskinesia 5 0.125 1 4.52e-4 8.26e-4 ✓ sig.