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 60

13 diseases · 29 shared-gene connections
13 Diseases
20 Unique genes
0.238 Avg. similarity score
Polycystic kidney disease with tuberous sclerosis Most-connected disease (8 links)
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Disease Searched: Adenomatous polyposis 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 ⇵
Polycystic kidney disease with tuberous sclerosis 8 8 2
Adenomatous polyposis 6 6 6
Polycystic kidneys, severe infantile with tuberous sclerosis 6 6 2
Tuberous sclerosis complex 6 6 6
Focal cortical dysplasia 5 5 7
Liver cyst 5 5 1
Renovascular hypertension 5 5 2
Congenital kidney anomaly 4 4 3
Pancreatic cyst 4 4 2
Xanthinuria 4 4 4
NTHL1-deficiency tumor predisposition syndrome 3 3 1
Colorectal adenomatous polyposis 1 1 1
Folic acid deficiency 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
PKD1 8 / 13 Congenital kidney anomaly, Focal cortical dysplasia, Liver cyst, Pancreatic cyst and 4 more
TSC2 6 / 13 Adenomatous polyposis, Focal cortical dysplasia, Polycystic kidney disease with tuberous sclerosis, Polycystic kidneys, severe infantile with tuberous sclerosis and 2 more
NTHL1 4 / 13 Adenomatous polyposis, Focal cortical dysplasia, NTHL1-deficiency tumor predisposition syndrome, Tuberous sclerosis complex
DHFR 2 / 13 Adenomatous polyposis, Folic acid deficiency
MUTYH 2 / 13 Adenomatous polyposis, Colorectal adenomatous polyposis
TSC1 2 / 13 Focal cortical dysplasia, Tuberous sclerosis complex
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 ⇵
Energy dependent regulation of mTOR by LKB1-AMPK
TSC2, MTOR, RHEB, TSC1
 Reactome 4 / 29 82.8× 1.29e-7 8.20e-6 ✓ sig.
Macroautophagy
TSC2, MTOR, RHEB, TSC1
 Reactome 4 / 68 35.3× 4.25e-6 1.70e-4 ✓ sig.
Inhibition of TSC complex formation by PKB
TSC2, TSC1
 Reactome 2 / 3 400× 7.90e-6 2.83e-4 ✓ sig.
Herpes simplex virus 1 infection
TSC2, MTOR, RHEB, TSC1, IFNG
 KEGG 5 / 182 16.5× 9.75e-6 3.34e-4 ✓ sig.
TP53 Regulates Metabolic Genes
TSC2, MTOR, RHEB, TSC1
 Reactome 4 / 86 27.9× 1.09e-5 3.67e-4 ✓ sig.
Longevity regulating pathway
TSC2, MTOR, RHEB, TSC1
 KEGG 4 / 90 26.7× 1.30e-5 4.25e-4 ✓ sig.
Choline metabolism in cancer
TSC2, MTOR, RHEB, TSC1
 KEGG 4 / 99 24.3× 1.90e-5 5.86e-4 ✓ sig.
HIF-1 signaling pathway
MTOR, NOS3, VHL, IFNG
 KEGG 4 / 110 21.8× 2.88e-5 8.23e-4 ✓ sig.
AMPK signaling pathway
TSC2, MTOR, RHEB, TSC1
 KEGG 4 / 122 19.7× 4.33e-5 1.16e-3 ✓ sig.
Insulin signaling pathway
TSC2, MTOR, RHEB, TSC1
 KEGG 4 / 138 17.4× 7.01e-5 1.70e-3 ✓ sig.
Displacement of DNA glycosylase by APEX1
MUTYH, NTHL1
 Reactome 2 / 9 133× 9.42e-5 2.16e-3 ✓ sig.
Phospholipase D signaling pathway
TSC2, MTOR, RHEB, TSC1
 KEGG 4 / 149 16.1× 9.44e-5 2.17e-3 ✓ sig.
Cellular senescence
TSC2, MTOR, RHEB, TSC1
 KEGG 4 / 157 15.3× 1.16e-4 2.55e-3 ✓ sig.
mTOR signaling pathway
TSC2, MTOR, RHEB, TSC1
 KEGG 4 / 158 15.2× 1.19e-4 2.60e-3 ✓ sig.
Autophagy - animal
TSC2, MTOR, RHEB, TSC1
 KEGG 4 / 169 14.2× 1.54e-4 3.20e-3 ✓ 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 ⇵
TORC1 signaling
TSC2, MTOR, RHEB, TSC1
 GO:0038202 4 / 67 55.8× 7.00e-7 6.25e-5 ✓ sig.
negative regulation of TORC1 signaling
TSC2, MTOR, TSC1, VHL
 GO:1904262 4 / 71 52.6× 8.85e-7 7.57e-5 ✓ sig.
positive regulation of TORC1 signaling
TSC2, MTOR, RHEB, TSC1
 GO:1904263 4 / 71 52.6× 8.85e-7 7.57e-5 ✓ sig.
positive regulation of translational initiation
TSC2, MTOR, RHEB
 GO:0045948 3 / 42 66.7× 1.17e-5 5.98e-4 ✓ sig.
negative regulation of translational initiation
TSC2, MTOR, RHEB
 GO:0045947 3 / 44 63.7× 1.35e-5 6.70e-4 ✓ sig.
regulation of macroautophagy
TSC2, MTOR, RHEB
 GO:0016241 3 / 57 49.2× 2.96e-5 1.22e-3 ✓ sig.
response to fluid shear stress
PKD1, NOS3
 GO:0034405 2 / 8 234× 3.04e-5 1.24e-3 ✓ sig.
negative regulation of cell size
MTOR, TSC1
 GO:0045792 2 / 9 208× 3.90e-5 1.52e-3 ✓ sig.
negative regulation of autophagy
MTOR, RHEB, VHL
 GO:0010507 3 / 73 38.4× 6.22e-5 2.16e-3 ✓ sig.
anoikis
TSC2, MTOR
 GO:0043276 2 / 12 156× 7.14e-5 2.40e-3 ✓ sig.
negative regulation of cell population proliferation
APC, TSC2, TSC1, NOS3, VHL
 GO:0008285 5 / 444 10.5× 8.55e-5 2.75e-3 ✓ sig.
cellular response to nutrient levels
TSC2, MTOR, RHEB
 GO:0031669 3 / 83 33.8× 9.12e-5 2.89e-3 ✓ sig.
negative regulation of macroautophagy
MTOR, TSC1
 GO:0016242 2 / 14 133× 9.83e-5 3.05e-3 ✓ sig.
cellular response to starvation
TSC2, MTOR, TSC1
 GO:0009267 3 / 90 31.1× 1.16e-4 3.45e-3 ✓ sig.
regulation of cell cycle
PKD1, TSC2, RHEB, TSC1
 GO:0051726 4 / 262 14.3× 1.53e-4 4.25e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Focal cortical dysplasia Tuberous sclerosis complex 0.400 4 2.24e-13 2.87e-12 ✓ sig.
Polycystic kidney disease with tuberous sclerosis Polycystic kidneys, severe infantile with tuberous sclerosis 0.667 2 8.44e-9 6.84e-8 ✓ sig.
Polycystic kidneys, severe infantile with tuberous sclerosis Tuberous sclerosis complex 0.286 2 1.27e-7 8.74e-7 ✓ sig.
Polycystic kidney disease with tuberous sclerosis Tuberous sclerosis complex 0.286 2 1.27e-7 8.74e-7 ✓ sig.
Focal cortical dysplasia Polycystic kidney disease with tuberous sclerosis 0.250 2 1.77e-7 1.19e-6 ✓ sig.
Focal cortical dysplasia Polycystic kidneys, severe infantile with tuberous sclerosis 0.250 2 1.77e-7 1.19e-6 ✓ sig.
Adenomatous polyposis Tuberous sclerosis complex 0.182 2 1.90e-6 1.06e-5 ✓ sig.
Adenomatous polyposis Focal cortical dysplasia 0.167 2 2.65e-6 1.45e-5 ✓ sig.
Liver cyst Polycystic kidneys, severe infantile with tuberous sclerosis 0.333 1 1.30e-4 3.91e-4 ✓ sig.
Liver cyst Pancreatic cyst 0.333 1 1.30e-4 3.91e-4 ✓ sig.
Liver cyst Renovascular hypertension 0.333 1 1.30e-4 3.91e-4 ✓ sig.
Liver cyst Polycystic kidney disease with tuberous sclerosis 0.333 1 1.30e-4 3.91e-4 ✓ sig.
Congenital kidney anomaly Liver cyst 0.250 1 1.95e-4 5.32e-4 ✓ sig.
Polycystic kidneys, severe infantile with tuberous sclerosis Renovascular hypertension 0.250 1 2.60e-4 6.48e-4 ✓ sig.
Polycystic kidney disease with tuberous sclerosis Renovascular hypertension 0.250 1 2.60e-4 6.48e-4 ✓ sig.
Pancreatic cyst Polycystic kidney disease with tuberous sclerosis 0.250 1 2.60e-4 6.48e-4 ✓ sig.
Pancreatic cyst Renovascular hypertension 0.250 1 2.60e-4 6.48e-4 ✓ sig.
Congenital kidney anomaly Pancreatic cyst 0.200 1 3.90e-4 8.64e-4 ✓ sig.
Congenital kidney anomaly Renovascular hypertension 0.200 1 3.90e-4 8.64e-4 ✓ sig.
Congenital kidney anomaly Polycystic kidney disease with tuberous sclerosis 0.200 1 3.90e-4 8.64e-4 ✓ sig.
Adenomatous polyposis Folic acid deficiency 0.143 1 3.90e-4 8.64e-4 ✓ sig.
Adenomatous polyposis Colorectal adenomatous polyposis 0.143 1 3.90e-4 8.64e-4 ✓ sig.
NTHL1-deficiency tumor predisposition syndrome Tuberous sclerosis complex 0.143 1 3.90e-4 8.64e-4 ✓ sig.
Adenomatous polyposis NTHL1-deficiency tumor predisposition syndrome 0.143 1 3.90e-4 8.64e-4 ✓ sig.
Focal cortical dysplasia NTHL1-deficiency tumor predisposition syndrome 0.125 1 4.55e-4 9.70e-4 ✓ sig.
Polycystic kidney disease with tuberous sclerosis Xanthinuria 0.167 1 5.19e-4 1.06e-3 ✓ sig.
Polycystic kidneys, severe infantile with tuberous sclerosis Xanthinuria 0.167 1 5.19e-4 1.06e-3 ✓ sig.
Adenomatous polyposis Xanthinuria 0.100 1 1.56e-3 2.37e-3 ✓ sig.
Tuberous sclerosis complex Xanthinuria 0.100 1 1.56e-3 2.37e-3 ✓ sig.