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 412

5 diseases · 5 shared-gene connections
5 Diseases
122 Unique genes
0.046 Avg. similarity score
Specific language disorder Most-connected disease (4 links)
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Disease Searched: Dyslexia 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 ⇵
Specific language disorder 4 4 19
Dyslexia 2 2 111
Male infertility acephalic spermatozoa 2 2 2
Cortical dysplasia-focal epilepsy syndrome 1 1 1
holocarboxylase synthetase deficiency 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
PMFBP1 3 / 5 Dyslexia, Male infertility acephalic spermatozoa, Specific language disorder
CCDC136 2 / 5 Dyslexia, Specific language disorder
CNTNAP2 2 / 5 Cortical dysplasia-focal epilepsy syndrome, Specific language disorder
COX6A1 2 / 5 Dyslexia, Specific language disorder
EPHA4 2 / 5 Dyslexia, Specific language disorder
FOXP2 2 / 5 Dyslexia, Specific language disorder
HLCS 2 / 5 holocarboxylase synthetase deficiency, Specific language disorder
INIP 2 / 5 Dyslexia, Specific language disorder
RBFOX2 2 / 5 Dyslexia, Specific language disorder
STK24 2 / 5 Dyslexia, Specific language disorder
ZFP64 2 / 5 Dyslexia, Specific language 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 ⇵
Cholesterol metabolism
ABCG5, ANGPTL4, APOB, APOE, CETP
 KEGG 5 / 51 9.7× 1.61e-4 3.32e-3 ✓ sig.
LDL remodeling
APOB, CETP
 Reactome 2 / 3 65.6× 3.05e-4 5.52e-3 ✓ sig.
DARPP-32 events
PDE4D, PPP1R1B, PPP2R1B
 Reactome 3 / 19 15.5× 8.80e-4 1.26e-2 ✓ sig.
Chylomicron clearance
APOB, APOE
 Reactome 2 / 5 39.4× 1.00e-3 1.39e-2 ✓ sig.
Dopaminergic synapse
DRD4, GNAQ, PPP1R1B, PPP2R1B, PPP2R3A, SLC6A3
 KEGG 6 / 132 4.5× 2.25e-3 2.54e-2 ✓ sig.
Chylomicron remodeling
APOB, APOE
 Reactome 2 / 9 21.9× 3.52e-3 3.49e-2 ✓ sig.
Chylomicron assembly
APOB, APOE
 Reactome 2 / 9 21.9× 3.52e-3 3.49e-2 ✓ sig.
HDL remodeling
APOE, CETP
 Reactome 2 / 10 19.7× 4.37e-3 4.06e-2 ✓ sig.
Scavenging by Class A Receptors
APOB, APOE
 Reactome 2 / 11 17.9× 5.30e-3 4.64e-2 ✓ sig.
Cell adhesion molecules
CNTNAP2, CD276, ITGAV, L1CAM, NRXN1, SLITRK2
 KEGG 6 / 160 3.7× 5.78e-3 4.93e-2 ✓ sig.
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
ABCG5, APOE, CETP
 Reactome 3 / 37 8.0× 6.18e-3 5.15e-2
Late Phase of HIV Life Cycle
NMT1
 Reactome 1 / 1 98.4× 1.02e-2 7.07e-2
Dopamine clearance from the synaptic cleft
SLC6A3
 Reactome 1 / 1 98.4× 1.02e-2 7.07e-2
Defective SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)
SLC6A3
 Reactome 1 / 1 98.4× 1.02e-2 7.07e-2
Polymerase switching on the C-strand of the telomere
CHTF8, RFC5
 Reactome 2 / 17 11.6× 1.26e-2 8.07e-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 ⇵
vocal learning
CNTNAP2, FOXP2, HTT, NRXN1
 GO:0042297 4 / 8 76.6× 1.19e-7 1.41e-5 ✓ sig.
proteoglycan biosynthetic process
CHST8, CHST9, CSGALNACT1, XYLT1
 GO:0030166 4 / 21 29.2× 9.50e-6 5.11e-4 ✓ sig.
positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity
HTT, HAP1
 GO:0031587 2 / 2 153× 4.23e-5 1.62e-3 ✓ sig.
triglyceride homeostasis
ABCG5, ANGPTL4, APOE, CETP
 GO:0070328 4 / 38 16.1× 1.08e-4 3.26e-3 ✓ sig.
axon development
L1CAM, MAPT, MARK2, NEUROD2
 GO:0061564 4 / 40 15.3× 1.32e-4 3.80e-3 ✓ sig.
low-density lipoprotein particle remodeling
APOB, APOE, CETP
 GO:0034374 3 / 16 28.7× 1.43e-4 4.03e-3 ✓ sig.
vocalization behavior
CNTNAP2, FOXP2, NRXN1
 GO:0071625 3 / 19 24.2× 2.44e-4 5.90e-3 ✓ sig.
negative regulation of protein secretion
CYP51A1, DRD4, APOE
 GO:0050709 3 / 22 20.9× 3.82e-4 8.13e-3 ✓ sig.
cellular response to amyloid-beta
EPHA4, FOXO3, APOB, APOE
 GO:1904646 4 / 53 11.6× 3.95e-4 8.33e-3 ✓ sig.
cellular response to lipoprotein particle stimulus
APOB, APOE
 GO:0071402 2 / 5 61.3× 4.17e-4 8.65e-3 ✓ sig.
NMDA glutamate receptor clustering
NRXN1, APOE
 GO:0097114 2 / 5 61.3× 4.17e-4 8.65e-3 ✓ sig.
antral ovarian follicle growth
FOXO3, ESR1
 GO:0001547 2 / 5 61.3× 4.17e-4 8.65e-3 ✓ sig.
lipoprotein biosynthetic process
APOB, APOE
 GO:0042158 2 / 6 51.1× 6.23e-4 1.14e-2 ✓ sig.
chondroitin sulfate proteoglycan biosynthetic process
CHST9, CSGALNACT1, XYLT1
 GO:0050650 3 / 26 17.7× 6.33e-4 1.15e-2 ✓ sig.
neuron projection development
CNTNAP2, L1CAM, MAPT, NRXN1, APOE, TNC
 GO:0031175 6 / 161 5.7× 6.61e-4 1.18e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Dyslexia Specific language disorder 0.074 9 3.29e-15 4.75e-14 ✓ sig.
Cortical dysplasia-focal epilepsy syndrome Specific language disorder 0.050 1 1.23e-3 1.98e-3 ✓ sig.
holocarboxylase synthetase deficiency Specific language disorder 0.050 1 1.23e-3 1.98e-3 ✓ sig.
Male infertility acephalic spermatozoa Specific language disorder 0.048 1 2.47e-3 3.37e-3 ✓ sig.
Dyslexia Male infertility acephalic spermatozoa 0.009 1 1.44e-2 1.60e-2 ✓ sig.