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 601

5 diseases · 7 shared-gene connections
5 Diseases
63 Unique genes
0.152 Avg. similarity score
Huntington disease Most-connected disease (4 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 ⇵
Huntington disease 4 4 61
Gastroschisis 3 3 1
Salt-sensitive hypertension 3 3 3
Ventriculomegaly 3 3 1
Lenz-majewski hyperostotic dwarfism 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
ADD1 4 / 5 Gastroschisis, Huntington disease, Salt-sensitive hypertension, Ventriculomegaly
PTDSS1 2 / 5 Huntington disease, Lenz-majewski hyperostotic dwarfism
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 ⇵
Cocaine addiction
BDNF, GRIN2A, GRIN2B, MAOA, MAOB
 KEGG 5 / 49 19.5× 5.40e-6 1.75e-4 ✓ sig.
Biogenic amines are oxidatively deaminated to aldehydes by MAOA and MAOB
MAOA, MAOB
 Reactome 2 / 2 191× 2.71e-5 6.69e-4 ✓ sig.
Amphetamine addiction
GRIN2A, GRIN2B, MAOA, MAOB, SIRT1
 KEGG 5 / 69 13.8× 2.93e-5 7.12e-4 ✓ sig.
Alcoholism
BDNF, GRIN2A, GRIN2B, MAOA, MAOB, NPY, SLC29A1
 KEGG 7 / 188 7.1× 5.44e-5 1.16e-3 ✓ sig.
Huntington disease
BDNF, GRIN2B, HAP1, HTT, MAP3K5, NRF1, PPARGC1A, TFAM
 KEGG 8 / 308 5.0× 1.94e-4 3.20e-3 ✓ sig.
Assembly and cell surface presentation of NMDA receptors
GRIN2A, GRIN2B
 Reactome 2 / 6 63.5× 4.01e-4 5.63e-3 ✓ sig.
Pathways of neurodegeneration - multiple diseases
BDNF, GRIN2A, GRIN2B, HAP1, HTT, IL6, MAP3K5, PRNP, PSEN2
 KEGG 9 / 480 3.6× 8.36e-4 9.88e-3 ✓ sig.
Alcoholic liver disease
IL6, MAP3K5, PPARGC1A, PRKAA1, SIRT1
 KEGG 5 / 144 6.6× 9.29e-4 1.07e-2 ✓ sig.
MAPK1 (ERK2) activation
IL6, IL6R
 Reactome 2 / 9 42.4× 9.52e-4 1.09e-2 ✓ sig.
MAPK3 (ERK1) activation
IL6, IL6R
 Reactome 2 / 10 38.1× 1.19e-3 1.29e-2 ✓ sig.
Longevity regulating pathway
IGF1, PPARGC1A, PRKAA1, SIRT1
 KEGG 4 / 90 8.5× 1.25e-3 1.35e-2 ✓ sig.
Interleukin-6 signaling
IL6, IL6R
 Reactome 2 / 11 34.7× 1.44e-3 1.50e-2 ✓ sig.
Transcriptional activation of mitochondrial biogenesis
NRF1, PPARGC1A, TFAM
 Reactome 3 / 51 11.2× 2.39e-3 2.17e-2 ✓ sig.
Phenylalanine metabolism
MAOA, MAOB
 KEGG 2 / 16 23.8× 3.10e-3 2.61e-2 ✓ sig.
Glutamatergic synapse
GLUL, GRIK2, GRIN2A, GRIN2B
 KEGG 4 / 116 6.6× 3.17e-3 2.65e-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 ⇵
cellular response to hydrogen peroxide
AIFM1, AQP1, HSF1, IL6, MAP3K5, PRKAA1, SIRT1
 GO:0070301 7 / 69 30.1× 3.22e-9 6.49e-7 ✓ sig.
negative regulation of apoptotic process
AQP1, ATF5, EIF2AK2, GDNF, HTT, IGF1, IL6, PRDM9, PRKAA1, PRNP, SIRT1
 GO:0043066 11 / 524 6.2× 1.25e-6 1.03e-4 ✓ sig.
regulation of neuronal synaptic plasticity
GRIN2A, GRIN2B, JPH3, NOG
 GO:0048168 4 / 26 45.6× 1.66e-6 1.30e-4 ✓ sig.
cell surface receptor signaling pathway via STAT
CNTF, IGF1, IL6, IL6R
 GO:0097696 4 / 28 42.4× 2.26e-6 1.68e-4 ✓ sig.
hepatic immune response
IL6, IL6R
 GO:0002384 2 / 2 297× 1.12e-5 5.94e-4 ✓ sig.
positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity
HAP1, HTT
 GO:0031587 2 / 2 297× 1.12e-5 5.94e-4 ✓ sig.
positive regulation of apoptotic process
AIFM1, DIABLO, GRIN2A, HTT, IL6, IP6K2, MAP3K5, SIRT1
 GO:0043065 8 / 326 7.3× 1.32e-5 6.76e-4 ✓ sig.
negative regulation of neuron apoptotic process
BDNF, CNTF, GDNF, GRIK2, PPARGC1A, SIRT1
 GO:0043524 6 / 160 11.1× 1.63e-5 7.92e-4 ✓ sig.
glutamate receptor signaling pathway
GRIK2, GRIN2A, GRIN2B
 GO:0007215 3 / 19 46.8× 3.40e-5 1.38e-3 ✓ sig.
protein destabilization
HTT, PRKAA1, PRNP, SIRT1
 GO:0031648 4 / 60 19.8× 4.96e-5 1.84e-3 ✓ sig.
monoatomic cation transmembrane transport
AQP1, GRIN2A, GRIN2B, TRPM1
 GO:0098655 4 / 61 19.5× 5.30e-5 1.93e-3 ✓ sig.
ionotropic glutamate receptor signaling pathway
GRIK2, GRIN2A, GRIN2B
 GO:0035235 3 / 23 38.7× 6.16e-5 2.16e-3 ✓ sig.
positive regulation of dopamine metabolic process
ABAT, NPY
 GO:0045964 2 / 4 148× 6.68e-5 2.29e-3 ✓ sig.
exploration behavior
ABAT, JPH3, NOG
 GO:0035640 3 / 25 35.6× 7.97e-5 2.61e-3 ✓ sig.
excitatory postsynaptic potential
GRIK2, GRIN2A, GRIN2B, SLC29A1
 GO:0060079 4 / 69 17.2× 8.60e-5 2.77e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Gastroschisis Ventriculomegaly 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Gastroschisis Salt-sensitive hypertension 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Salt-sensitive hypertension Ventriculomegaly 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Gastroschisis Huntington disease 0.016 1 3.94e-3 4.83e-3 ✓ sig.
Huntington disease Lenz-majewski hyperostotic dwarfism 0.016 1 3.94e-3 4.83e-3 ✓ sig.
Huntington disease Ventriculomegaly 0.016 1 3.94e-3 4.83e-3 ✓ sig.
Huntington disease Salt-sensitive hypertension 0.016 1 1.18e-2 1.30e-2 ✓ sig.