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 166

9 diseases · 17 shared-gene connections
9 Diseases
77 Unique genes
0.199 Avg. similarity score
Constitutional mismatch repair deficiency Most-connected disease (7 links)
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Disease Searched: ciliary dyskinesia, primary, 47, and lissencephaly 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 ⇵
Constitutional mismatch repair deficiency 7 7 13
Muir-torre syndrome 6 6 4
mismatch repair cancer syndrome 1 5 5 4
Rhabdomyosarcoma 4 4 27
Intellectual developmental disorder dysmorphic behavioral 3 3 3
Lynch syndrome 3 3 49
Turcot syndrome 3 3 3
Cystic leukoencephalopathy 2 2 2
ciliary dyskinesia, primary, 47, and lissencephaly 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
MLH1 6 / 9 Constitutional mismatch repair deficiency, Lynch syndrome, mismatch repair cancer syndrome 1, Muir-torre syndrome and 2 more
MSH6 6 / 9 Constitutional mismatch repair deficiency, Intellectual developmental disorder dysmorphic behavioral, Lynch syndrome, mismatch repair cancer syndrome 1 and 2 more
PMS2 6 / 9 Constitutional mismatch repair deficiency, Lynch syndrome, mismatch repair cancer syndrome 1, Muir-torre syndrome and 2 more
MSH2 5 / 9 Constitutional mismatch repair deficiency, Lynch syndrome, mismatch repair cancer syndrome 1, Muir-torre syndrome and 1 more
APC 3 / 9 Constitutional mismatch repair deficiency, Lynch syndrome, Turcot syndrome
RNASET2 3 / 9 Constitutional mismatch repair deficiency, Cystic leukoencephalopathy, Lynch syndrome
ASTE1 2 / 9 Constitutional mismatch repair deficiency, Lynch syndrome
FBXO11 2 / 9 Intellectual developmental disorder dysmorphic behavioral, Lynch syndrome
SLC22A9 2 / 9 Constitutional mismatch repair deficiency, Lynch syndrome
TAF1B 2 / 9 Constitutional mismatch repair deficiency, Lynch syndrome
TGFBR2 2 / 9 Constitutional mismatch repair deficiency, Lynch syndrome
TP73 2 / 9 ciliary dyskinesia, primary, 47, and lissencephaly, Rhabdomyosarcoma
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 14 / 87 25.1× 2.14e-16 8.93e-14 ✓ sig.
Hepatocellular carcinoma
RB1, TGFBR2, APC, TP53, SMARCA4, GSTM1, GSTT1, KRAS, PIK3CA, SMAD2, SMAD3, SMAD4
 KEGG 16 / 170 14.7× 8.24e-15 2.58e-12 ✓ sig.
Cellular senescence
ATM, CHEK2, RB1, TGFBR2, TP53, E2F4, KRAS, MRE11, PIK3CA, SMAD2, SMAD3, TGFBR1
 KEGG 15 / 157 14.9× 4.97e-14 1.32e-11 ✓ sig.
Pathways in cancer
MLH1, MSH2, MSH6, RB1, TGFBR2, APC, TP53, CDKN1B, GSTM1, GSTT1, KRAS, MSH3
 KEGG 22 / 533 6.4× 1.17e-12 2.50e-10 ✓ sig.
Gastric cancer
MLH1, RB1, TGFBR2, APC, TP53, CDKN1B, KRAS, PIK3CA, SMAD2, SMAD3, SMAD4, TGFBR1
 KEGG 13 / 150 13.5× 9.85e-12 1.80e-9 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
TGFBR2, CDKN1B, KRAS, PIK3CA, SMAD2, SMAD3, SMAD4, TGFBR1, HRAS, VEGFA, FOXO1
 KEGG 11 / 101 17.0× 3.60e-11 5.83e-9 ✓ sig.
Pancreatic cancer
RB1, TGFBR2, TP53, KRAS, PIK3CA, SMAD2, SMAD3, SMAD4, TGFBR1, VEGFA
 KEGG 10 / 77 20.3× 4.99e-11 7.78e-9 ✓ sig.
Chronic myeloid leukemia
RB1, TGFBR2, TP53, CDKN1B, KRAS, PIK3CA, SMAD3, SMAD4, TGFBR1, HRAS
 KEGG 10 / 77 20.3× 4.99e-11 7.78e-9 ✓ sig.
Mismatch repair
MLH1, MLH3, MSH2, MSH6, PMS2, EXO1, MSH3
 KEGG 7 / 23 47.5× 7.61e-11 1.14e-8 ✓ sig.
Cell cycle
ATM, CHEK2, RB1, TFDP1, TP53, CDKN1B, E2F4, SMAD2, SMAD3, SMAD4, BUB1B, CDKN1C
 KEGG 12 / 158 11.8× 3.11e-10 4.10e-8 ✓ sig.
Platinum drug resistance
ATM, MLH1, MSH2, MSH6, TP53, GSTM1, GSTT1, MSH3, PIK3CA
 KEGG 9 / 75 18.7× 1.01e-9 1.18e-7 ✓ sig.
Human T-cell leukemia virus 1 infection
ATM, CHEK2, RB1, TGFBR2, TP53, KRAS, PIK3CA, SMAD2, SMAD3, SMAD4, TGFBR1, BUB1B
 KEGG 13 / 224 9.1× 1.49e-9 1.67e-7 ✓ sig.
TGF-beta receptor signaling activates SMADs
TGFBR2, SMAD2, SMAD3, SMAD4, TGFBR1
 Reactome 5 / 12 65.0× 7.26e-9 6.95e-7 ✓ sig.
Homologous DNA Pairing and Strand Exchange
ATM, PALB2, RAD51D, EXO1, MRE11, NBN
 Reactome 6 / 25 37.4× 9.16e-9 8.46e-7 ✓ sig.
FoxO signaling pathway
ATM, TGFBR2, CDKN1B, KRAS, PIK3CA, SMAD3, SMAD4, TGFBR1, HRAS, FOXO1
 KEGG 10 / 133 11.7× 1.15e-8 1.03e-6 ✓ 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, TP73, SETD2
 GO:0006298 11 / 30 89.0× 1.42e-19 2.06e-16 ✓ sig.
DNA damage response
ATM, CHEK2, MLH1, MLH3, MSH2, MSH6, MUTYH, PALB2, PMS1, PMS2, RAD51D, APC
 GO:0006974 24 / 577 10.1× 4.18e-18 4.92e-15 ✓ sig.
DNA repair
ATM, CHEK2, MLH1, MLH3, MSH2, MSH6, MUTYH, PALB2, PMS1, PMS2, RAD51D, POLE
 GO:0006281 19 / 420 11.0× 4.94e-15 3.46e-12 ✓ sig.
positive regulation of transcription by RNA polymerase II
ATM, EPCAM, RB1, KMT2D, TFDP1, TP53, NFKBIZ, SMARCA4, ACVR2A, E2F4, RNASEL, SMAD2
 GO:0045944 26 / 1,208 5.2× 8.65e-13 4.03e-10 ✓ sig.
somatic recombination of immunoglobulin gene segments
MLH1, MSH2, MSH6, PMS2, MSH3
 GO:0016447 5 / 6 202× 6.23e-12 2.42e-9 ✓ sig.
isotype switching
MLH1, MSH2, MSH6, NFKBIZ, EXO1, NBN
 GO:0045190 6 / 19 76.6× 1.04e-10 3.04e-8 ✓ sig.
activin receptor signaling pathway
TGFBR2, ACVR2A, SMAD2, SMAD3, SMAD4, TGFBR1
 GO:0032924 6 / 22 66.2× 2.84e-10 7.36e-8 ✓ sig.
in utero embryonic development
MSH2, PALB2, TGFBR2, TP53, SMAD2, SMAD3, SMAD4, TGFBR1, IGF2, NBN, PTCH1, VEGFA
 GO:0001701 12 / 252 11.6× 4.71e-10 1.16e-7 ✓ sig.
regulation of cell cycle
ATM, MSH2, RAD51D, RB1, TFDP1, TP53, CDKN1B, TGFBR1, CDKN1C, HRAS, NBN, TP73
 GO:0051726 12 / 262 11.1× 7.35e-10 1.71e-7 ✓ sig.
somatic hypermutation of immunoglobulin genes
MLH1, MSH2, MSH6, PMS2, EXO1
 GO:0016446 5 / 14 86.7× 2.02e-9 4.21e-7 ✓ sig.
positive regulation of DNA-templated transcription
CHEK2, TFDP1, TP53, SMARCA4, SMAD2, SMAD3, SMAD4, TCF4, TGFBR1, CDKN1C, PTCH1, FOXO1
 GO:0045893 17 / 778 5.3× 1.34e-8 2.20e-6 ✓ sig.
SMAD protein signal transduction
TGFBR2, SMAD2, SMAD3, SMAD4, WWTR1
 GO:0060395 5 / 25 48.5× 5.19e-8 7.06e-6 ✓ sig.
double-strand break repair
ATM, CHEK2, MSH2, TP53, XRCC4, MRE11, NBN
 GO:0006302 7 / 87 19.5× 6.85e-8 8.90e-6 ✓ sig.
regulation of gene expression
ATM, TGFBR2, NFKBIZ, PIK3CA, RNASEL, SMAD4, TGFBR1, PAX7, TP73, MYOD1, SETD2, YAP1
 GO:0010468 12 / 402 7.2× 8.69e-8 1.09e-5 ✓ sig.
intrinsic apoptotic signaling pathway in response to DNA damage
ATM, CHEK2, MLH1, MSH2, MSH6, TP73
 GO:0008630 6 / 54 27.0× 8.86e-8 1.11e-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 0.189 10 1.13e-23 2.57e-22 ✓ sig.
mismatch repair cancer syndrome 1 Muir-torre syndrome 0.800 4 4.27e-16 6.52e-15 ✓ sig.
Constitutional mismatch repair deficiency Muir-torre syndrome 0.286 4 3.05e-13 3.86e-12 ✓ sig.
Constitutional mismatch repair deficiency mismatch repair cancer syndrome 1 0.286 4 3.05e-13 3.86e-12 ✓ sig.
Muir-torre syndrome Rhabdomyosarcoma 0.143 4 7.50e-12 8.30e-11 ✓ sig.
mismatch repair cancer syndrome 1 Rhabdomyosarcoma 0.143 4 7.50e-12 8.30e-11 ✓ sig.
Lynch syndrome Muir-torre syndrome 0.080 4 9.05e-11 9.07e-10 ✓ sig.
Constitutional mismatch repair deficiency Turcot syndrome 0.214 3 4.70e-10 4.39e-9 ✓ sig.
Constitutional mismatch repair deficiency Rhabdomyosarcoma 0.108 4 5.30e-9 4.47e-8 ✓ sig.
mismatch repair cancer syndrome 1 Turcot syndrome 0.333 2 1.52e-7 1.03e-6 ✓ sig.
Muir-torre syndrome Turcot syndrome 0.333 2 1.52e-7 1.03e-6 ✓ sig.
Intellectual developmental disorder dysmorphic behavioral Muir-torre syndrome 0.143 1 7.79e-4 1.41e-3 ✓ sig.
Intellectual developmental disorder dysmorphic behavioral mismatch repair cancer syndrome 1 0.143 1 7.79e-4 1.41e-3 ✓ sig.
Constitutional mismatch repair deficiency Cystic leukoencephalopathy 0.067 1 1.69e-3 2.53e-3 ✓ sig.
ciliary dyskinesia, primary, 47, and lissencephaly Rhabdomyosarcoma 0.036 1 1.75e-3 2.61e-3 ✓ sig.
Constitutional mismatch repair deficiency Intellectual developmental disorder dysmorphic behavioral 0.063 1 2.53e-3 3.45e-3 ✓ sig.
Cystic leukoencephalopathy Lynch syndrome 0.020 1 6.35e-3 7.62e-3 ✓ sig.