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 209

8 diseases · 19 shared-gene connections
8 Diseases
39 Unique genes
0.233 Avg. similarity score
Familial temporal lobe epilepsy Most-connected disease (7 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 ⇵
Familial temporal lobe epilepsy 7 7 7
Epilepsy with auditory features 6 6 4
Lateral temporal lobe epilepsy 6 6 4
Sacroiliac arthritis 5 5 1
Sacroiliac joint synovitis 5 5 1
lissencephaly with cerebellar hypoplasia 5 5 2
autosomal dominant epilepsy with auditory features 3 3 1
Temporal lobe epilepsy 1 1 33

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

Gene ⇵ Member diseases ⇵ Linked diseases
RELN 7 / 8 Epilepsy with auditory features, Familial temporal lobe epilepsy, Lateral temporal lobe epilepsy, lissencephaly with cerebellar hypoplasia and 3 more
LGI1 4 / 8 autosomal dominant epilepsy with auditory features, Epilepsy with auditory features, Familial temporal lobe epilepsy, Lateral temporal lobe epilepsy
GAL 3 / 8 Familial temporal lobe epilepsy, Lateral temporal lobe epilepsy, Temporal lobe epilepsy
CPA6 2 / 8 Familial temporal lobe epilepsy, Temporal lobe epilepsy
DEPDC5 2 / 8 Epilepsy with auditory features, Lateral temporal lobe epilepsy
MICAL1 2 / 8 Epilepsy with auditory features, Familial temporal lobe epilepsy
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 ⇵
Neuroactive ligand-receptor interaction
GAL, GRIN2A, BDKRB1, BDKRB2, CNR1, GRM1, GRM2, GRM3, GRM4, GRM5, NPY, NPY2R
 KEGG 16 / 370 13.3× 9.44e-15 2.97e-12 ✓ sig.
G alpha (i) signalling events
GAL, BDKRB1, BDKRB2, CNR1, GRM2, GRM3, GRM4, NPY, NPY2R, PDYN
 Reactome 10 / 249 12.4× 4.59e-9 4.39e-7 ✓ sig.
Glutamatergic synapse
GRIN2A, GRM1, GRM2, GRM3, GRM4, GRM5, SLC1A1
 KEGG 7 / 116 18.6× 7.78e-8 5.25e-6 ✓ sig.
Calcium signaling pathway
GRIN2A, BDKRB1, BDKRB2, GRM1, GRM5, KDR, P2RX4, P2RX7, VEGFA
 KEGG 9 / 254 10.9× 8.95e-8 5.94e-6 ✓ sig.
Class C/3 (Metabotropic glutamate/pheromone receptors)
GRM1, GRM2, GRM3, GRM4, GRM5
 Reactome 5 / 38 40.5× 1.28e-7 8.13e-6 ✓ sig.
Cocaine addiction
GRIN2A, GRM2, GRM3, PDYN, CDK5
 KEGG 5 / 49 31.4× 4.76e-7 2.56e-5 ✓ sig.
Peptide ligand-binding receptors
GAL, BDKRB1, BDKRB2, NPY, NPY2R, PDYN
 Reactome 6 / 106 17.4× 1.06e-6 5.12e-5 ✓ sig.
Phospholipase D signaling pathway
GRM1, GRM2, GRM3, GRM4, GRM5
 KEGG 5 / 149 10.3× 1.13e-4 2.47e-3 ✓ sig.
Cation-coupled Chloride cotransporters
SLC12A2, SLC12A5
 Reactome 2 / 7 88.0× 2.14e-4 4.11e-3 ✓ sig.
VEGF binds to VEGFR leading to receptor dimerization
KDR, VEGFA
 Reactome 2 / 8 77.0× 2.84e-4 5.15e-3 ✓ sig.
Platelet homeostasis
P2RX4, P2RX7
 Reactome 2 / 8 77.0× 2.84e-4 5.15e-3 ✓ sig.
Rap1 signaling pathway
GRIN2A, CNR1, KDR, TEK, VEGFA
 KEGG 5 / 211 7.3× 5.65e-4 8.76e-3 ✓ sig.
Elevation of cytosolic Ca2+ levels
P2RX4, P2RX7
 Reactome 2 / 13 47.4× 7.84e-4 1.13e-2 ✓ sig.
Pathways of neurodegeneration - multiple diseases
GRIN2A, COX3, GRM1, GRM5, MAPT, PDYN, CDK5
 KEGG 7 / 480 4.5× 7.89e-4 1.14e-2 ✓ sig.
VEGFR2 mediated cell proliferation
KDR, VEGFA
 Reactome 2 / 14 44.0× 9.12e-4 1.27e-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 ⇵
chemical synaptic transmission
GRIN2A, GRM1, GRM2, GRM3, GRM4, GRM5, KCNC4, NPY, PDYN, SLC12A5, SLC1A1, CDK5
 GO:0007268 12 / 236 24.4× 3.60e-14 2.14e-11 ✓ sig.
adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway
GRM1, GRM2, GRM3, GRM4, GRM5
 GO:0007196 5 / 9 266× 3.80e-12 1.52e-9 ✓ sig.
regulation of synaptic transmission, glutamatergic
GRM1, GRM2, GRM3, GRM4, GRM5, CDK5
 GO:0051966 6 / 33 87.1× 5.87e-11 1.78e-8 ✓ sig.
G protein-coupled glutamate receptor signaling pathway
GRM1, GRM2, GRM3, GRM4, GRM5
 GO:0007216 5 / 14 171× 5.99e-11 1.81e-8 ✓ sig.
sensory perception of pain
GRIN2A, GRM1, P2RX4, P2RX7, TRPV1, CDK5
 GO:0019233 6 / 44 65.3× 3.68e-10 9.14e-8 ✓ sig.
excitatory postsynaptic potential
GRIN2A, P2RX4, P2RX7, TRPV1, CDK5
 GO:0060079 5 / 69 34.7× 3.09e-7 3.13e-5 ✓ sig.
positive regulation of MAPK cascade
GRM1, GRM4, GRM5, KDR, P2RX7, TEK, VEGFA
 GO:0043410 7 / 224 15.0× 3.59e-7 3.54e-5 ✓ sig.
learning or memory
GRIN2A, GRM5, KCNAB1, MAPT, SLC1A1
 GO:0007611 5 / 72 33.3× 3.83e-7 3.74e-5 ✓ sig.
synaptic signaling via neuropeptide
GRM1, NPY, NPY2R
 GO:0099538 3 / 9 160× 7.00e-7 6.22e-5 ✓ sig.
monoatomic ion transport
GRIN2A, KCNAB1, KCNC4, NALCN, P2RX4, P2RX7, SLC12A2, SLC12A5, SLC1A1, TRPV1
 GO:0006811 10 / 667 7.2× 7.81e-7 6.79e-5 ✓ sig.
locomotory behavior
RELN, GRM1, GRM5, NPY2R, SLC1A1
 GO:0007626 5 / 99 24.2× 1.88e-6 1.37e-4 ✓ sig.
positive regulation of endothelial cell chemotaxis
KDR, P2RX4, VEGFA
 GO:2001028 3 / 13 111× 2.37e-6 1.65e-4 ✓ sig.
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
RELN, GRM2, KDR, P2RX4, TEK, VEGFA
 GO:0051897 6 / 217 13.2× 5.42e-6 3.20e-4 ✓ sig.
regulation of postsynaptic membrane potential
GRIN2A, GRM1, GRM5, CDK5
 GO:0060078 4 / 59 32.5× 6.79e-6 3.83e-4 ✓ sig.
cellular response to ATP
P2RX4, P2RX7, TRPV1
 GO:0071318 3 / 19 75.7× 7.96e-6 4.36e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Epilepsy with auditory features Lateral temporal lobe epilepsy 0.500 3 2.63e-11 2.94e-10 ✓ sig.
Epilepsy with auditory features Familial temporal lobe epilepsy 0.333 3 2.30e-10 2.34e-9 ✓ sig.
Familial temporal lobe epilepsy Lateral temporal lobe epilepsy 0.333 3 2.30e-10 2.34e-9 ✓ sig.
Familial temporal lobe epilepsy Temporal lobe epilepsy 0.079 3 3.12e-7 2.12e-6 ✓ sig.
Sacroiliac arthritis Sacroiliac joint synovitis 0.500 1 6.49e-5 2.34e-4 ✓ sig.
lissencephaly with cerebellar hypoplasia Sacroiliac joint synovitis 0.333 1 1.30e-4 3.90e-4 ✓ sig.
lissencephaly with cerebellar hypoplasia Sacroiliac arthritis 0.333 1 1.30e-4 3.90e-4 ✓ sig.
autosomal dominant epilepsy with auditory features Lateral temporal lobe epilepsy 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Lateral temporal lobe epilepsy Sacroiliac joint synovitis 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Lateral temporal lobe epilepsy Sacroiliac arthritis 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Epilepsy with auditory features Sacroiliac joint synovitis 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Epilepsy with auditory features Sacroiliac arthritis 0.200 1 2.60e-4 6.40e-4 ✓ sig.
autosomal dominant epilepsy with auditory features Epilepsy with auditory features 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Familial temporal lobe epilepsy Sacroiliac joint synovitis 0.125 1 4.55e-4 9.55e-4 ✓ sig.
Familial temporal lobe epilepsy Sacroiliac arthritis 0.125 1 4.55e-4 9.55e-4 ✓ sig.
autosomal dominant epilepsy with auditory features Familial temporal lobe epilepsy 0.125 1 4.55e-4 9.55e-4 ✓ sig.
Epilepsy with auditory features lissencephaly with cerebellar hypoplasia 0.167 1 5.19e-4 1.04e-3 ✓ sig.
Lateral temporal lobe epilepsy lissencephaly with cerebellar hypoplasia 0.167 1 5.19e-4 1.04e-3 ✓ sig.
Familial temporal lobe epilepsy lissencephaly with cerebellar hypoplasia 0.111 1 9.09e-4 1.56e-3 ✓ sig.