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 144

11 diseases · 23 shared-gene connections
11 Diseases
53 Unique genes
0.262 Avg. similarity score
Turcot syndrome Most-connected disease (7 links)
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Disease Searched: Thrombocytopenia 10 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 ⇵
Turcot syndrome 7 7 5
Mismatch repair cancer syndrome 1 6 6 4
Muir-torre syndrome 6 6 4
Constitutional mismatch repair deficiency 5 5 13
Lynch syndrome 5 5 49
Colorectal cancer, hereditary nonpolyposis, type 4 4 4 1
Mismatch repair cancer syndrome 4 4 4 1
Mismatch repair cancer syndrome 2 3 3 1
Cystic leukoencephalopathy 2 2 2
Hereditary nonpolyposis colon cancer 2 2 8
Thrombocytopenia 10 2 2 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
PMS2 7 / 11 Colorectal cancer, hereditary nonpolyposis, type 4, Constitutional mismatch repair deficiency, Lynch syndrome, Mismatch repair cancer syndrome 1 and 3 more
MSH2 6 / 11 Constitutional mismatch repair deficiency, Lynch syndrome, Mismatch repair cancer syndrome 1, Mismatch repair cancer syndrome 2 and 2 more
MLH1 5 / 11 Constitutional mismatch repair deficiency, Lynch syndrome, Mismatch repair cancer syndrome 1, Muir-torre syndrome and 1 more
MSH6 5 / 11 Constitutional mismatch repair deficiency, Lynch syndrome, Mismatch repair cancer syndrome 1, Muir-torre syndrome and 1 more
APC 3 / 11 Constitutional mismatch repair deficiency, Lynch syndrome, Turcot syndrome
PTPRJ 3 / 11 Hereditary nonpolyposis colon cancer, Lynch syndrome, Thrombocytopenia 10
RNASET2 3 / 11 Constitutional mismatch repair deficiency, Cystic leukoencephalopathy, Lynch syndrome
ASTE1 2 / 11 Constitutional mismatch repair deficiency, Lynch syndrome
CDKN1B 2 / 11 Hereditary nonpolyposis colon cancer, Lynch syndrome
CHEK2 2 / 11 Hereditary nonpolyposis colon cancer, Lynch syndrome
EPHX1 2 / 11 Hereditary nonpolyposis colon cancer, Lynch syndrome
FAN1 2 / 11 Hereditary nonpolyposis colon cancer, Lynch syndrome
NFKBIZ 2 / 11 Hereditary nonpolyposis colon cancer, Lynch syndrome
SLC22A9 2 / 11 Constitutional mismatch repair deficiency, Lynch syndrome
SMARCA4 2 / 11 Hereditary nonpolyposis colon cancer, Lynch syndrome
TAF1B 2 / 11 Constitutional mismatch repair deficiency, Lynch syndrome
TGFBR2 2 / 11 Constitutional mismatch repair deficiency, Lynch syndrome
XRCC4 2 / 11 Hereditary nonpolyposis colon cancer, Lynch 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 ⇵
Colorectal cancer
MLH1, MSH2, MSH6, TGFBR2, APC, TP53, KRAS, MSH3, PIK3CA, SMAD2, SMAD3, SMAD4
 KEGG 13 / 87 33.9× 3.96e-17 1.81e-14 ✓ sig.
Hepatocellular carcinoma
RB1, TGFBR2, APC, TP53, SMARCA4, GSTM1, GSTT1, KRAS, PIK3CA, SMAD2, SMAD3, SMAD4
 KEGG 13 / 170 17.3× 2.97e-13 6.22e-11 ✓ sig.
Gastric cancer
MLH1, RB1, TGFBR2, APC, TP53, CDKN1B, KRAS, PIK3CA, SMAD2, SMAD3, SMAD4, TGFBR1
 KEGG 12 / 150 18.1× 1.59e-12 2.88e-10 ✓ sig.
Cellular senescence
ATM, CHEK2, RB1, TGFBR2, TP53, E2F4, KRAS, MRE11, PIK3CA, SMAD2, SMAD3, TGFBR1
 KEGG 12 / 157 17.3× 2.74e-12 4.71e-10 ✓ sig.
Mismatch repair
MLH1, MLH3, MSH2, MSH6, PMS2, EXO1, MSH3
 KEGG 7 / 23 69.0× 5.02e-12 8.19e-10 ✓ sig.
Platinum drug resistance
ATM, MLH1, MSH2, MSH6, TP53, GSTM1, GSTT1, MSH3, PIK3CA
 KEGG 9 / 75 27.2× 3.13e-11 4.25e-9 ✓ sig.
Pancreatic cancer
RB1, TGFBR2, TP53, KRAS, PIK3CA, SMAD2, SMAD3, SMAD4, TGFBR1
 KEGG 9 / 77 26.5× 4.00e-11 5.27e-9 ✓ sig.
Chronic myeloid leukemia
RB1, TGFBR2, TP53, CDKN1B, KRAS, PIK3CA, SMAD3, SMAD4, TGFBR1
 KEGG 9 / 77 26.5× 4.00e-11 5.27e-9 ✓ sig.
Pathways in cancer
MLH1, MSH2, MSH6, RB1, TGFBR2, APC, TP53, CDKN1B, GSTM1, GSTT1, KRAS, MSH3
 KEGG 17 / 533 7.2× 5.71e-11 7.15e-9 ✓ sig.
TGF-beta receptor signaling activates SMADs
TGFBR2, SMAD2, SMAD3, SMAD4, TGFBR1
 Reactome 5 / 12 94.4× 1.07e-9 9.87e-8 ✓ sig.
Cell cycle
ATM, CHEK2, RB1, TFDP1, TP53, CDKN1B, E2F4, SMAD2, SMAD3, SMAD4
 KEGG 10 / 158 14.3× 1.40e-9 1.26e-7 ✓ sig.
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
MLH1, MSH2, MSH6, PMS2, EXO1
 Reactome 5 / 14 80.9× 2.68e-9 2.27e-7 ✓ sig.
Human T-cell leukemia virus 1 infection
ATM, CHEK2, RB1, TGFBR2, TP53, KRAS, PIK3CA, SMAD2, SMAD3, SMAD4, TGFBR1
 KEGG 11 / 224 11.1× 2.85e-9 2.40e-7 ✓ sig.
SMAD2/3 Phosphorylation Motif Mutants in Cancer
TGFBR2, SMAD2, SMAD3, TGFBR1
 Reactome 4 / 6 151× 5.04e-9 4.00e-7 ✓ sig.
TGFBR1 KD Mutants in Cancer
TGFBR2, SMAD2, SMAD3, TGFBR1
 Reactome 4 / 6 151× 5.04e-9 4.00e-7 ✓ 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 ⇵
mismatch repair
MLH1, MLH3, MSH2, MSH6, MUTYH, PMS1, PMS2, EXO1, MSH3
 GO:0006298 9 / 30 106× 7.93e-17 7.97e-14 ✓ sig.
DNA damage response
ATM, CHEK2, MLH1, MLH3, MSH2, MSH6, MUTYH, PALB2, PMS1, PMS2, RAD51D, APC
 GO:0006974 19 / 577 11.6× 6.72e-16 5.65e-13 ✓ sig.
DNA repair
ATM, CHEK2, MLH1, MLH3, MSH2, MSH6, MUTYH, PALB2, PMS1, PMS2, RAD51D, POLE
 GO:0006281 17 / 420 14.3× 1.06e-15 8.66e-13 ✓ sig.
somatic recombination of immunoglobulin gene segments
MLH1, MSH2, MSH6, PMS2, MSH3
 GO:0016447 5 / 6 294× 9.05e-13 4.30e-10 ✓ sig.
activin receptor signaling pathway
TGFBR2, ACVR2A, SMAD2, SMAD3, SMAD4, TGFBR1
 GO:0032924 6 / 22 96.2× 2.80e-11 9.66e-9 ✓ sig.
somatic hypermutation of immunoglobulin genes
MLH1, MSH2, MSH6, PMS2, EXO1
 GO:0016446 5 / 14 126× 2.97e-10 8.11e-8 ✓ sig.
isotype switching
MLH1, MSH2, MSH6, NFKBIZ, EXO1
 GO:0045190 5 / 19 92.8× 1.71e-9 3.70e-7 ✓ sig.
reciprocal meiotic recombination
ATM, MLH1, MLH3, RAD51D, MRE11
 GO:0007131 5 / 33 53.4× 3.38e-8 5.09e-6 ✓ sig.
negative regulation of cell growth
RB1, TP53, CDKN1B, PTPRJ, SMARCA4, SMAD3, SMAD4
 GO:0030308 7 / 115 21.5× 3.39e-8 5.11e-6 ✓ sig.
gastrulation
TGFBR2, TP53, SMAD2, SMAD3, SMAD4
 GO:0007369 5 / 38 46.4× 7.07e-8 9.53e-6 ✓ sig.
positive regulation of SMAD protein signal transduction
TGFBR2, ACVR2A, SMAD3, SMAD4, TGFBR1
 GO:0060391 5 / 42 42.0× 1.19e-7 1.47e-5 ✓ sig.
double-strand break repair
ATM, CHEK2, MSH2, TP53, XRCC4, MRE11
 GO:0006302 6 / 87 24.3× 1.65e-7 1.93e-5 ✓ sig.
double-strand break repair via nonhomologous end joining
ATM, MLH1, ASTE1, XRCC4, MRE11
 GO:0006303 5 / 45 39.2× 1.70e-7 1.97e-5 ✓ sig.
maintenance of DNA repeat elements
MSH2, MSH6, MSH3
 GO:0043570 3 / 5 212× 2.15e-7 2.39e-5 ✓ sig.
positive regulation of isotype switching to IgA isotypes
MLH1, MSH2, PMS2
 GO:0048298 3 / 6 176× 4.28e-7 4.27e-5 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Constitutional mismatch repair deficiency Lynch syndrome 0.200 10 1.56e-24 2.63e-23 ✓ sig.
Hereditary nonpolyposis colon cancer Lynch syndrome 0.167 8 3.84e-21 5.84e-20 ✓ sig.
Constitutional mismatch repair deficiency Turcot syndrome 0.385 5 1.07e-16 1.39e-15 ✓ sig.
Mismatch repair cancer syndrome 1 Muir-torre syndrome 0.800 4 4.17e-16 5.27e-15 ✓ sig.
Muir-torre syndrome Turcot syndrome 0.667 4 2.09e-15 2.56e-14 ✓ sig.
Mismatch repair cancer syndrome 1 Turcot syndrome 0.667 4 2.09e-15 2.56e-14 ✓ sig.
Constitutional mismatch repair deficiency Muir-torre syndrome 0.308 4 2.07e-13 2.31e-12 ✓ sig.
Constitutional mismatch repair deficiency Mismatch repair cancer syndrome 1 0.308 4 2.07e-13 2.31e-12 ✓ sig.
Lynch syndrome Turcot syndrome 0.104 5 2.07e-13 2.31e-12 ✓ sig.
Colorectal cancer, hereditary nonpolyposis, type 4 Mismatch repair cancer syndrome 4 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Mismatch repair cancer syndrome 1 Mismatch repair cancer syndrome 4 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Mismatch repair cancer syndrome 4 Muir-torre syndrome 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Mismatch repair cancer syndrome 2 Muir-torre syndrome 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Mismatch repair cancer syndrome 1 Mismatch repair cancer syndrome 2 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Colorectal cancer, hereditary nonpolyposis, type 4 Mismatch repair cancer syndrome 1 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Colorectal cancer, hereditary nonpolyposis, type 4 Muir-torre syndrome 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Mismatch repair cancer syndrome 4 Turcot syndrome 0.167 1 3.23e-4 6.41e-4 ✓ sig.
Colorectal cancer, hereditary nonpolyposis, type 4 Turcot syndrome 0.167 1 3.23e-4 6.41e-4 ✓ sig.
Mismatch repair cancer syndrome 2 Turcot syndrome 0.167 1 3.23e-4 6.41e-4 ✓ sig.
Hereditary nonpolyposis colon cancer Thrombocytopenia 10 0.111 1 5.17e-4 9.13e-4 ✓ sig.
Constitutional mismatch repair deficiency Cystic leukoencephalopathy 0.071 1 1.55e-3 2.19e-3 ✓ sig.
Lynch syndrome Thrombocytopenia 10 0.021 1 3.03e-3 3.86e-3 ✓ sig.
Cystic leukoencephalopathy Lynch syndrome 0.020 1 6.06e-3 7.13e-3 ✓ sig.