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 125

10 diseases · 13 shared-gene connections
10 Diseases
133 Unique genes
0.194 Avg. similarity score
Sleep 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 ⇵
Sleep disorder 5 5 11
Avoidant restrictive food intake disorder 4 4 1
Cavitary optic disk anomaly 4 4 2
Dysbetalipoproteinemia 4 4 1
Bile duct calculus 3 3 4
Sleep apnea 2 2 49
Cavitary optic disc anomalies 1 1 1
Delayed sleep phase syndrome 1 1 1
Obstructive sleep apnea syndrome 1 1 81
leukodystrophy, hypomyelinating, 16 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
APOE 6 / 10 Avoidant restrictive food intake disorder, Bile duct calculus, Cavitary optic disk anomaly, Dysbetalipoproteinemia and 2 more
SLC39A8 3 / 10 Obstructive sleep apnea syndrome, Sleep apnea, Sleep disorder
BFSP1 2 / 10 Sleep apnea, Sleep disorder
BTBD9 2 / 10 Sleep apnea, Sleep disorder
CRY1 2 / 10 Delayed sleep phase syndrome, Sleep disorder
DLEU7 2 / 10 Obstructive sleep apnea syndrome, Sleep apnea
ETV5 2 / 10 Obstructive sleep apnea syndrome, Sleep apnea
FTO 2 / 10 Obstructive sleep apnea syndrome, Sleep apnea
MEIS1 2 / 10 Sleep apnea, Sleep disorder
METTL15 2 / 10 Obstructive sleep apnea syndrome, Sleep apnea
MMP19 2 / 10 Cavitary optic disc anomalies, Cavitary optic disk anomaly
MSRB3 2 / 10 Obstructive sleep apnea syndrome, Sleep apnea
NRG1 2 / 10 Obstructive sleep apnea syndrome, Sleep apnea
TMEM106B 2 / 10 leukodystrophy, hypomyelinating, 16, Sleep disorder
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 ⇵
Circadian rhythm
CRY1, BHLHE40, NFIL3, RORC
 KEGG 4 / 34 10.6× 5.15e-4 8.15e-3 ✓ sig.
Renin secretion
PLCB1, ACE, ADRB1, EDN1, EDNRA
 KEGG 5 / 69 6.5× 9.84e-4 1.34e-2 ✓ sig.
Interleukin-18 signaling
IL37, IL18
 Reactome 2 / 8 22.6× 3.26e-3 3.27e-2 ✓ sig.
SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion
NRP1, SEMA3A
 Reactome 2 / 10 18.1× 5.17e-3 4.47e-2 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
PLCB1, BCL2, EDN1, NOS3, TNF
 KEGG 5 / 101 4.5× 5.24e-3 4.50e-2 ✓ sig.
Interleukin-4 and Interleukin-13 signaling
BCL2, IL18, MMP9, TNF, RORC
 Reactome 5 / 108 4.2× 6.93e-3 5.44e-2
African trypanosomiasis
PLCB1, IL18, TNF
 KEGG 3 / 37 7.3× 7.84e-3 5.89e-2
Defective CYP17A1 causes Adrenal hyperplasia 5 (AH5)
CYP17A1
 Reactome 1 / 1 90.3× 1.11e-2 7.30e-2
Defective UGT1A1 causes hyperbilirubinemia
UGT1A1
 Reactome 1 / 1 90.3× 1.11e-2 7.30e-2
Serotonin clearance from the synaptic cleft
SLC6A4
 Reactome 1 / 1 90.3× 1.11e-2 7.30e-2
Sema3A PAK dependent Axon repulsion
NRP1, SEMA3A
 Reactome 2 / 15 12.0× 1.16e-2 7.51e-2
CRMPs in Sema3A signaling
NRP1, SEMA3A
 Reactome 2 / 16 11.3× 1.32e-2 8.06e-2
Relaxin signaling pathway
ARRB1, PLCB1, EDN1, MMP9, NOS3
 KEGG 5 / 130 3.5× 1.47e-2 8.61e-2
Fluid shear stress and atherosclerosis
BCL2, EDN1, MMP9, NOS3, TNF
 KEGG 5 / 141 3.2× 2.02e-2 1.03e-1
NOSIP mediated eNOS trafficking
NOS3
 Reactome 1 / 2 45.2× 2.20e-2 1.09e-1

Enriched GO Terms (Biological Process, a second line of biological evidence)

GO term ⇵ GO ID ⇵ Overlap genes ⇵ Fold enrichment ⇵ P-value ⇵ FDR q-value ⇵
axonogenesis involved in innervation
NRP1, SEMA3A, EDN1, EDNRA
 GO:0060385 4 / 10 56.2× 4.98e-7 4.67e-5 ✓ sig.
axon guidance
CDH4, LMX1A, NRP1, NRXN3, BDNF, NOG, ROBO2, SEMA3A, EDN1, EDNRA
 GO:0007411 10 / 192 7.3× 1.17e-6 9.42e-5 ✓ sig.
circadian rhythm
CRY1, SLC6A4, TNF, AANAT, BHLHE40, NFIL3, RORC
 GO:0007623 7 / 82 12.0× 1.93e-6 1.40e-4 ✓ sig.
vasoconstriction
CRP, EDN1, EDNRA, SLC6A4
 GO:0042310 4 / 18 31.2× 6.95e-6 3.90e-4 ✓ sig.
cellular response to human chorionic gonadotropin stimulus
EDN1, EDNRA
 GO:0044751 2 / 2 141× 5.03e-5 1.81e-3 ✓ sig.
pharyngeal arch artery morphogenesis
NOG, EDN1, EDNRA
 GO:0061626 3 / 11 38.3× 5.58e-5 1.96e-3 ✓ sig.
cellular response to toxic substance
EDN1, EDNRA, TNF
 GO:0097237 3 / 12 35.1× 7.40e-5 2.42e-3 ✓ sig.
negative regulation of apoptotic signaling pathway
BCL2, BDNF, NOG, TNF
 GO:2001234 4 / 36 15.6× 1.21e-4 3.50e-3 ✓ sig.
axon extension
CDH4, NRP1, EDN1, EDNRA
 GO:0048675 4 / 37 15.2× 1.35e-4 3.78e-3 ✓ sig.
basal dendrite arborization
NRP1, SEMA3A
 GO:0150020 2 / 3 93.7× 1.50e-4 4.10e-3 ✓ sig.
semaphorin-plexin signaling pathway involved in axon guidance
EDN1, EDNRA
 GO:1902287 2 / 3 93.7× 1.50e-4 4.10e-3 ✓ sig.
endothelin receptor signaling pathway involved in heart process
EDN1, EDNRA
 GO:0086101 2 / 3 93.7× 1.50e-4 4.10e-3 ✓ sig.
angiogenesis
MMP19, NRP1, NRXN3, FGF18, MEIS1, IL18, EDNRA, LEPR, NOS3
 GO:0001525 9 / 284 4.5× 2.00e-4 5.05e-3 ✓ sig.
positive regulation of membrane protein ectodomain proteolysis
APOE, RGMA, TNF
 GO:0051044 3 / 17 24.8× 2.23e-4 5.44e-3 ✓ sig.
sympathetic nervous system development
NRP1, SEMA3A, EDNRA
 GO:0048485 3 / 17 24.8× 2.23e-4 5.44e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Obstructive sleep apnea syndrome Sleep apnea 0.056 7 6.15e-9 5.45e-8 ✓ sig.
Sleep apnea Sleep disorder 0.070 4 2.94e-8 2.35e-7 ✓ sig.
Avoidant restrictive food intake disorder Dysbetalipoproteinemia 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Avoidant restrictive food intake disorder Cavitary optic disk anomaly 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Cavitary optic disc anomalies Cavitary optic disk anomaly 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Cavitary optic disk anomaly Dysbetalipoproteinemia 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Avoidant restrictive food intake disorder Bile duct calculus 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Bile duct calculus Dysbetalipoproteinemia 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Bile duct calculus Cavitary optic disk anomaly 0.167 1 5.19e-4 1.04e-3 ✓ sig.
Avoidant restrictive food intake disorder Sleep disorder 0.083 1 7.14e-4 1.31e-3 ✓ sig.
Delayed sleep phase syndrome Sleep disorder 0.083 1 7.14e-4 1.31e-3 ✓ sig.
Dysbetalipoproteinemia Sleep disorder 0.083 1 7.14e-4 1.31e-3 ✓ sig.
leukodystrophy, hypomyelinating, 16 Sleep disorder 0.083 1 7.14e-4 1.31e-3 ✓ sig.