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 435

6 diseases · 8 shared-gene connections
6 Diseases
9 Unique genes
0.216 Avg. similarity score
Amme complex Most-connected disease (4 links)
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Disease Searched: Alport syndrome with mental retardation midface hypoplasia and elliptocytosis 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 ⇵
Amme complex 4 4 3
Non-syndromic X-linked intellectual disability 4 4 7
Alport syndrome with mental retardation midface hypoplasia and elliptocytosis 3 3 1
Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome 3 3 1
Fraxe intellectual disability 1 1 1
Midface hypoplasia-hearing impairment-elliptocytosis-nephrocalcinosis syndrome 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
ACSL4 4 / 6 Alport syndrome with mental retardation midface hypoplasia and elliptocytosis, Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome, Amme complex, Non-syndromic X-linked intellectual disability
AFF2 2 / 6 Fraxe intellectual disability, Non-syndromic X-linked intellectual disability
AMMECR1 2 / 6 Amme complex, Midface hypoplasia-hearing impairment-elliptocytosis-nephrocalcinosis syndrome
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 ⇵
Intracellular metabolism of fatty acids regulates insulin secretion
ACSL4
 Reactome 1 / 3 445× 2.25e-3 1.98e-2 ✓ sig.
Phase 3 - rapid repolarisation
KCNE5
 Reactome 1 / 8 167× 5.98e-3 3.93e-2 ✓ sig.
Activation of Ca-permeable Kainate Receptor
DLG3
 Reactome 1 / 12 111× 8.96e-3 5.11e-2
Trafficking of GluR2-containing AMPA receptors
TSPAN7
 Reactome 1 / 17 78.5× 1.27e-2 6.36e-2
Fatty acid biosynthesis
ACSL4
 KEGG 1 / 18 74.1× 1.34e-2 6.57e-2
Synaptic adhesion-like molecules
DLG3
 Reactome 1 / 21 63.5× 1.56e-2 7.23e-2
Unblocking of NMDA receptors, glutamate binding and activation
DLG3
 Reactome 1 / 22 60.7× 1.64e-2 7.41e-2
Synthesis of very long-chain fatty acyl-CoAs
ACSL4
 Reactome 1 / 22 60.7× 1.64e-2 7.41e-2
Phase 2 - plateau phase
KCNE5
 Reactome 1 / 25 53.4× 1.86e-2 7.99e-2
Neurexins and neuroligins
DLG3
 Reactome 1 / 32 41.7× 2.37e-2 9.26e-2
Ferroptosis
ACSL4
 KEGG 1 / 42 31.8× 3.10e-2 1.08e-1
Fatty acid degradation
ACSL4
 KEGG 1 / 43 31.0× 3.18e-2 1.10e-1
Fatty acid metabolism
ACSL4
 KEGG 1 / 57 23.4× 4.19e-2 1.29e-1
Adipocytokine signaling pathway
ACSL4
 KEGG 1 / 70 19.1× 5.13e-2 1.45e-1
PPAR signaling pathway
ACSL4
 KEGG 1 / 76 17.6× 5.56e-2 1.52e-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 ⇵
negative regulation of prostaglandin secretion
ACSL4
 GO:0032307 1 / 1 2,076× 4.82e-4 9.07e-3 ✓ sig.
regulation of opioid receptor signaling pathway
SYP
 GO:2000474 1 / 2 1,038× 9.63e-4 1.40e-2 ✓ sig.
nuclear speck organization
AFF2
 GO:0035063 1 / 4 519× 1.93e-3 2.04e-2 ✓ sig.
synaptic vesicle membrane organization
SYP
 GO:0048499 1 / 5 415× 2.41e-3 2.30e-2 ✓ sig.
regulation of atrial cardiac muscle cell membrane repolarization
KCNE5
 GO:0060372 1 / 6 346× 2.89e-3 2.52e-2 ✓ sig.
negative regulation of protein targeting to membrane
GDI1
 GO:0090315 1 / 6 346× 2.89e-3 2.52e-2 ✓ sig.
positive regulation of toll-like receptor signaling pathway
GDI1
 GO:0034123 1 / 6 346× 2.89e-3 2.52e-2 ✓ sig.
negative regulation of protein localization
GDI1
 GO:1903828 1 / 6 346× 2.89e-3 2.52e-2 ✓ sig.
negative regulation of potassium ion export across plasma membrane
KCNE5
 GO:1903765 1 / 6 346× 2.89e-3 2.52e-2 ✓ sig.
long-chain fatty-acyl-CoA metabolic process
ACSL4
 GO:0035336 1 / 7 297× 3.37e-3 2.73e-2 ✓ sig.
negative regulation of mitochondrial fusion
HUWE1
 GO:0010637 1 / 8 260× 3.85e-3 2.90e-2 ✓ sig.
negative regulation of peroxisome proliferator activated receptor signaling pathway
HUWE1
 GO:0035359 1 / 8 260× 3.85e-3 2.90e-2 ✓ sig.
embryonic process involved in female pregnancy
ACSL4
 GO:0060136 1 / 8 260× 3.85e-3 2.90e-2 ✓ sig.
receptor localization to synapse
DLG3
 GO:0097120 1 / 9 231× 4.33e-3 3.08e-2 ✓ sig.
atrial cardiac muscle cell action potential
KCNE5
 GO:0086014 1 / 9 231× 4.33e-3 3.08e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Alport syndrome with mental retardation midface hypoplasia and elliptocytosis Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Alport syndrome with mental retardation midface hypoplasia and elliptocytosis Amme complex 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome Amme complex 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Amme complex Midface hypoplasia-hearing impairment-elliptocytosis-nephrocalcinosis syndrome 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Alport syndrome with mental retardation midface hypoplasia and elliptocytosis Non-syndromic X-linked intellectual disability 0.125 1 4.52e-4 8.26e-4 ✓ sig.
Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome Non-syndromic X-linked intellectual disability 0.125 1 4.52e-4 8.26e-4 ✓ sig.
Fraxe intellectual disability Non-syndromic X-linked intellectual disability 0.125 1 4.52e-4 8.26e-4 ✓ sig.
Amme complex Non-syndromic X-linked intellectual disability 0.100 1 1.36e-3 1.97e-3 ✓ sig.