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 303

6 diseases · 7 shared-gene connections
6 Diseases
221 Unique genes
0.050 Avg. similarity score
Bone fracture 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 ⇵
Bone fracture 4 4 68
Bone disease 3 3 82
Dupuytren contracture 3 3 89
temtamy preaxial brachydactyly syndrome 2 2 1
Metabolic bone disorder 1 1 14
Parkinsonism with polyneuropathy 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
CHSY1 3 / 6 Bone fracture, Dupuytren contracture, temtamy preaxial brachydactyly syndrome
ESR1 3 / 6 Bone disease, Bone fracture, Metabolic bone disorder
FMN2 3 / 6 Bone disease, Bone fracture, Dupuytren contracture
SFRP4 3 / 6 Bone disease, Bone fracture, Dupuytren contracture
STARD3NL 3 / 6 Bone disease, Bone fracture, Dupuytren contracture
ALPL 2 / 6 Bone disease, Metabolic bone disorder
ANKRD11 2 / 6 Bone disease, Metabolic bone disorder
AXIN1 2 / 6 Bone disease, Bone fracture
CCDC170 2 / 6 Bone disease, Bone fracture
CTC1 2 / 6 Bone disease, Metabolic bone disorder
CYP19A1 2 / 6 Bone disease, Bone fracture
CYP27A1 2 / 6 Bone disease, Metabolic bone disorder
CYP2R1 2 / 6 Bone disease, Metabolic bone disorder
DHCR7 2 / 6 Bone disease, Metabolic bone disorder
GC 2 / 6 Bone disease, Metabolic bone disorder
IGF1 2 / 6 Bone disease, Metabolic bone disorder
JAG1 2 / 6 Bone disease, Dupuytren contracture
KCNMA1 2 / 6 Bone disease, Metabolic bone disorder
LRP2 2 / 6 Bone disease, Metabolic bone disorder
MMP2 2 / 6 Bone disease, Metabolic bone disorder
PHOSPHO1 2 / 6 Bone disease, Metabolic bone disorder
PRKAR1B 2 / 6 Bone fracture, Dupuytren contracture
RAB31 2 / 6 Bone fracture, Dupuytren contracture
RSPO3 2 / 6 Bone disease, Bone fracture
SEM1 2 / 6 Bone disease, Bone fracture
SLC20A1 2 / 6 Bone disease, Metabolic bone disorder
SUPT3H 2 / 6 Bone disease, Bone fracture
UQCRC1 2 / 6 Bone fracture, Parkinsonism with polyneuropathy
ZBTB40 2 / 6 Bone disease, Dupuytren contracture
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 ⇵
Proteoglycans in cancer
WNT1, ESR1, FGF2, MMP2, ANK1, IGF2, TGFB2, IGF1, FZD7, ITGA2, ITGB3, WNT16
 KEGG 18 / 204 4.8× 3.85e-8 2.83e-6 ✓ sig.
Wnt signaling pathway
AXIN1, RSPO3, SFRP4, TCF7L2, WNT1, FZD7, LRP5, NFATC1, SOST, WNT16, NFATC2, RSPO2
 KEGG 15 / 174 4.7× 7.35e-7 3.73e-5 ✓ sig.
RUNX1 regulates transcription of genes involved in WNT signaling
AXIN1, RSPO3, ESR1, CBFB
 Reactome 4 / 6 36.2× 1.63e-6 7.40e-5 ✓ sig.
Breast cancer
AXIN1, TCF7L2, WNT1, ESR1, FGF2, JAG1, IGF1, FZD7, LRP5, WNT16, MTOR, WNT2
 KEGG 13 / 148 4.8× 3.33e-6 1.35e-4 ✓ sig.
Gastric cancer
AXIN1, TCF7L2, WNT1, FGF2, TGFBR2, TGFB2, FZD7, LRP5, WNT16, FGFR2, MTOR, WNT2
 KEGG 13 / 150 4.7× 3.87e-6 1.54e-4 ✓ sig.
Pathways in cancer
ABL1, AXIN1, TCF7L2, WNT1, BMP2, CDKN2A, ESR1, FGF2, JAG1, MMP2, TGFBR2, CHUK
 KEGG 26 / 533 2.7× 5.35e-6 2.01e-4 ✓ sig.
Signaling pathways regulating pluripotency of stem cells
AXIN1, WNT1, FGF2, BMPR1B, DLX5, ZIC3, IGF1, FZD7, WNT16, FGFR2, WNT2, WNT7B
 KEGG 12 / 144 4.5× 1.37e-5 4.36e-4 ✓ sig.
Hepatocellular carcinoma
AXIN1, TCF7L2, WNT1, CDKN2A, TGFBR2, IGF2, TGFB2, FZD7, LRP5, WNT16, MTOR, WNT2
 KEGG 13 / 170 4.2× 1.52e-5 4.76e-4 ✓ sig.
Basal cell carcinoma
AXIN1, TCF7L2, WNT1, BMP2, FZD7, WNT16, WNT2, WNT7B
 KEGG 8 / 63 6.9× 1.88e-5 5.70e-4 ✓ sig.
Hippo signaling pathway
AXIN1, TCF7L2, WNT1, BMP2, TGFBR2, BMPR1B, TGFB2, FZD7, WNT16, LIMD1, WNT2, WNT7B
 KEGG 12 / 157 4.2× 3.26e-5 8.96e-4 ✓ sig.
Human papillomavirus infection
AXIN1, HLA-B, TCF7L2, WNT1, JAG1, CHUK, FZD7, ITGA2, ITGB3, WNT16, IRF1, ITGA11
 KEGG 18 / 333 2.9× 4.35e-5 1.14e-3 ✓ sig.
RUNX1 regulates estrogen receptor mediated transcription
AXIN1, ESR1, CBFB
 Reactome 3 / 6 27.2× 1.18e-4 2.56e-3 ✓ sig.
VEGFA-VEGFR2 Pathway
PTK2B, ITGB3, ELMO1, KDR, PTK2, PXN, WASF3
 Reactome 7 / 62 6.1× 1.35e-4 2.86e-3 ✓ sig.
Endocrine resistance
CDKN2A, ESR1, JAG1, MMP2, IGF1, ADCY4, MTOR, PTK2
 KEGG 8 / 99 4.4× 4.71e-4 7.62e-3 ✓ sig.
Cushing syndrome
AXIN1, TCF7L2, WNT1, AHR, CDKN2A, FZD7, WNT16, ADCY4, WNT2, WNT7B
 KEGG 10 / 155 3.5× 5.84e-4 8.99e-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 ⇵
canonical Wnt signaling pathway
AXIN1, RSPO3, SFRP4, TCF7L2, WNT1, FGF2, EXT1, FZD7, LRP5, SOST, WNT16, RSPO2
 GO:0060070 15 / 105 12.1× 1.67e-12 7.29e-10 ✓ sig.
skeletal system development
SFRP4, BMP2, LTBP3, DLX5, IFT80, RPS6KA3, SH3PXD2B, TGFB2, TRPS1, ZIC3, PTH, ALPL
 GO:0001501 16 / 151 9.0× 3.18e-11 1.02e-8 ✓ sig.
positive regulation of transcription by RNA polymerase II
ABL1, CDC5L, DAB2IP, DDN, TCF7L2, WNT1, AHR, BMP2, CDKN2A, ESR1, FGF2, JAG1
 GO:0045944 43 / 1,208 3.0× 6.25e-11 1.88e-8 ✓ sig.
positive regulation of fibroblast proliferation
ABL1, WNT1, ESR1, PDGFA, CTC1, IGF1, AQP1, ITGB3, DDR2, WNT2
 GO:0048146 10 / 55 15.4× 8.02e-10 1.84e-7 ✓ sig.
positive regulation of osteoblast differentiation
BMP2, FGF2, JAG1, BMPR1B, NPPC, IGF1, LRP5, TENT5A, DDR2, SFRP2, WNT7B
 GO:0045669 11 / 78 11.9× 1.92e-9 3.99e-7 ✓ sig.
bone morphogenesis
SFRP4, LTBP3, DLX5, IFT80, CHSY1, EXT1, LRP5, FGFR2
 GO:0060349 8 / 32 21.1× 2.78e-9 5.52e-7 ✓ sig.
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
TCF7L2, FGF2, PTK2B, IGF2, ITGB1BP1, TGFB2, PDGFA, IGF1, ADTRP, WNT16, DDR2, FER
 GO:0051897 16 / 217 6.2× 6.85e-9 1.23e-6 ✓ sig.
ossification
BMP2, CBFB, DLX5, IFT80, IGF2, NPPC, SLC34A1, TMCO1, EXT1, SOST, DDR2, MMP14
 GO:0001503 12 / 110 9.2× 7.05e-9 1.27e-6 ✓ sig.
cranial skeletal system development
COLEC10, TGFB2, ZIC3, LRP2, EXT1, FGFR2
 GO:1904888 6 / 18 28.2× 4.21e-8 5.86e-6 ✓ sig.
osteoblast differentiation
BMP2, FGF2, BMPR1B, CBFB, DLX5, IFT80, IGF2, ALPL, IGF1, ITGA11, RSPO2, TNC
 GO:0001649 12 / 137 7.4× 8.43e-8 1.04e-5 ✓ sig.
cell fate commitment
WNT1, BMP2, EXT1, SOX6, WNT16, FGFR2, KDR, WNT2, WNT7B
 GO:0045165 9 / 75 10.1× 2.46e-7 2.58e-5 ✓ sig.
bone development
WNT1, BMP2, BMPR1B, IFT80, SH3PXD2B, PDGFA, LRP5, FGFR2, MMP14
 GO:0060348 9 / 76 10.0× 2.76e-7 2.84e-5 ✓ sig.
angiogenesis
DAB2IP, RSPO3, FGF2, JAG1, LEPR, MMP2, PTK2B, ITGB1BP1, NPPC, PDGFA, COL15A1, ITGB3
 GO:0001525 16 / 284 4.8× 2.90e-7 2.96e-5 ✓ sig.
bone mineralization
ZBTB40, BMP2, LTBP3, PTH, ALPL, PHOSPHO1, FGFR2, RSPO2
 GO:0030282 8 / 56 12.1× 2.94e-7 3.00e-5 ✓ sig.
positive regulation of cell population proliferation
WNT1, BMP2, FGF2, LEPR, PTK2B, TGFBR2, IGF2, ITGB1BP1, TGFB2, PDGFA, IGF1, ITGB3
 GO:0008284 22 / 532 3.5× 3.80e-7 3.71e-5 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Bone disease Metabolic bone disorder 0.169 14 4.58e-33 1.65e-31 ✓ sig.
Bone disease Bone fracture 0.071 10 2.36e-12 2.88e-11 ✓ sig.
Bone fracture Dupuytren contracture 0.039 6 2.58e-6 1.49e-5 ✓ sig.
Bone disease Dupuytren contracture 0.030 5 1.11e-4 3.90e-4 ✓ sig.
Bone fracture Parkinsonism with polyneuropathy 0.014 1 4.42e-3 5.52e-3 ✓ sig.
Bone fracture temtamy preaxial brachydactyly syndrome 0.014 1 4.42e-3 5.52e-3 ✓ sig.
Dupuytren contracture temtamy preaxial brachydactyly syndrome 0.011 1 5.78e-3 7.00e-3 ✓ sig.