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 76

13 diseases · 23 shared-gene connections
13 Diseases
74 Unique genes
0.114 Avg. similarity score
Ectodermal dysplasia Most-connected disease (8 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 ⇵
Ectodermal dysplasia 8 8 32
Tooth agenesis 6 6 41
Anhidrotic ectodermal dysplasia 5 5 1
Christ-siemens-touraine syndrome 5 5 5
Hypohidrotic ectodermal dysplasia 5 5 7
X-linked hypohidrotic ectodermal dysplasia 5 5 2
Craniofrontonasal dysplasia 3 3 4
ectodermal dysplasia 10b, hypohidrotic/hair/tooth type, autosomal recessive 3 3 1
ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type 2 2 1
Absence of fingerprints-congenital milia syndrome 1 1 1
X-linked intellectual disability-cerebellar hypoplasia syndrome 1 1 1
tooth agenesis, selective, 3 1 1 1
tooth agenesis, selective, 9 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
EDA 6 / 13 Anhidrotic ectodermal dysplasia, Christ-siemens-touraine syndrome, Craniofrontonasal dysplasia, Ectodermal dysplasia and 2 more
EDAR 4 / 13 Christ-siemens-touraine syndrome, Ectodermal dysplasia, ectodermal dysplasia 10b, hypohidrotic/hair/tooth type, autosomal recessive, Hypohidrotic ectodermal dysplasia
EDARADD 4 / 13 Christ-siemens-touraine syndrome, Ectodermal dysplasia, Hypohidrotic ectodermal dysplasia, Tooth agenesis
KDF1 3 / 13 Ectodermal dysplasia, ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type, Hypohidrotic ectodermal dysplasia
WNT10A 3 / 13 Ectodermal dysplasia, Hypohidrotic ectodermal dysplasia, Tooth agenesis
CSTB 2 / 13 Ectodermal dysplasia, Hypohidrotic ectodermal dysplasia
EDA2R 2 / 13 Christ-siemens-touraine syndrome, X-linked hypohidrotic ectodermal dysplasia
GREM2 2 / 13 Tooth agenesis, tooth agenesis, selective, 9
LRP6 2 / 13 Hypohidrotic ectodermal dysplasia, Tooth agenesis
OPHN1 2 / 13 Craniofrontonasal dysplasia, X-linked intellectual disability-cerebellar hypoplasia syndrome
PAX9 2 / 13 Tooth agenesis, tooth agenesis, selective, 3
RANBP2 2 / 13 Christ-siemens-touraine syndrome, Ectodermal dysplasia
SMARCAD1 2 / 13 Absence of fingerprints-congenital milia syndrome, Ectodermal dysplasia
TSPEAR 2 / 13 Ectodermal dysplasia, Tooth agenesis
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 ⇵
Basal cell carcinoma
WNT10A, BMP2, BMP4, GLI3, WNT10B, LEF1, AXIN2
 KEGG 7 / 63 18.0× 1.06e-7 6.89e-6 ✓ sig.
Pathways in cancer
LRP6, TRAF6, WNT10A, BMP2, BMP4, GLI3, MMP9, WNT10B, RHOA, LEF1, IKBKG, NFKBIA
 KEGG 16 / 533 4.9× 1.12e-7 7.20e-6 ✓ sig.
Signaling pathways regulating pluripotency of stem cells
SMARCAD1, WNT10A, BMP4, WNT10B, AXIN2, FGFR1, SMAD2, BMPR2
 KEGG 8 / 144 9.0× 2.72e-6 1.15e-4 ✓ sig.
NF-kappa B signaling pathway
EDA, EDAR, EDARADD, TRAF6, EDA2R, IKBKG, NFKBIA
 KEGG 7 / 105 10.8× 3.55e-6 1.43e-4 ✓ sig.
Hippo signaling pathway
WNT10A, BMP2, BMP4, WNT10B, LEF1, AXIN2, SMAD2, BMPR2
 KEGG 8 / 157 8.3× 5.18e-6 1.96e-4 ✓ sig.
Negative regulation of TCF-dependent signaling by WNT ligand antagonists
LRP6, DKK1, KREMEN1
 Reactome 3 / 8 60.9× 1.23e-5 3.98e-4 ✓ sig.
TNFs bind their physiological receptors
EDA, EDAR, EDARADD, EDA2R
 Reactome 4 / 29 22.4× 2.81e-5 7.88e-4 ✓ sig.
Prostate cancer
MMP9, LEF1, IKBKG, NFKBIA, FGFR1, TGFA
 KEGG 6 / 98 9.9× 3.00e-5 8.33e-4 ✓ sig.
TGF-beta signaling pathway
BMP2, BMP4, GREM2, RHOA, SMAD2, BMPR2
 KEGG 6 / 108 9.0× 5.19e-5 1.32e-3 ✓ sig.
Hepatocellular carcinoma
LRP6, WNT10A, WNT10B, LEF1, AXIN2, SMAD2, TGFA
 KEGG 7 / 170 6.7× 8.16e-5 1.90e-3 ✓ sig.
Wnt signaling pathway
LRP6, WNT10A, DKK1, WNT10B, RHOA, LEF1, AXIN2
 KEGG 7 / 174 6.5× 9.44e-5 2.14e-3 ✓ sig.
Formation of the cornified envelope
KRT16, KRT17, PKP1, KRT85, KRT74, DSP
 Reactome 6 / 130 7.5× 1.45e-4 3.04e-3 ✓ sig.
Colorectal cancer
RHOA, LEF1, AXIN2, SMAD2, TGFA
 KEGG 5 / 87 9.3× 1.93e-4 3.81e-3 ✓ sig.
SLIT2:ROBO1 increases RHOA activity
RHOA, ROBO1
 Reactome 2 / 4 81.1× 2.23e-4 4.27e-3 ✓ sig.
Adherens junction
NECTIN1, RHOA, LEF1, NECTIN4, FGFR1
 KEGG 5 / 93 8.7× 2.64e-4 4.86e-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 ⇵
odontogenesis of dentin-containing tooth
EDA, EDAR, TRAF6, BMP2, BMP4, GLI3, MSX1, TP63, LEF1, FOXI3
 GO:0042475 10 / 56 45.1× 1.55e-14 9.75e-12 ✓ sig.
odontogenesis
EDA, WNT10A, BMP4, MSX1, PAX9, RHOA, AXIN2, MSX2
 GO:0042476 8 / 36 56.1× 1.13e-12 5.18e-10 ✓ sig.
embryonic limb morphogenesis
BMP4, DKK1, GLI3, MSX1, TP63, LEF1, FGFR1, MSX2
 GO:0030326 8 / 59 34.2× 7.73e-11 2.26e-8 ✓ sig.
hair follicle development
EDA, EDAR, WNT10A, DKK1, TP63, HOXC13, FOXI3
 GO:0001942 7 / 48 36.8× 7.39e-10 1.71e-7 ✓ sig.
positive regulation of gene expression
EDA, EDAR, WNT10A, BMP2, BMP4, DKK1, PKP1, LEF1, IKBKG, CDH3, LIMS1, ROBO1
 GO:0010628 14 / 504 7.0× 9.32e-9 1.61e-6 ✓ sig.
heart induction
BMP2, BMP4, DKK1, ROBO1
 GO:0003129 4 / 8 126× 1.57e-8 2.52e-6 ✓ sig.
positive regulation of osteoblast differentiation
BMP2, BMP4, GLI3, WNT10B, TP63, MSX2, BMPR2
 GO:0045669 7 / 78 22.7× 2.41e-8 3.66e-6 ✓ sig.
positive regulation of transcription by RNA polymerase II
SMARCAD1, LRP6, TRAF6, BMP2, BMP4, GLI3, MSX1, PAX9, WNT10B, PKP1, TP63, LEF1
 GO:0045944 20 / 1,208 4.2× 2.85e-8 4.20e-6 ✓ sig.
osteoblast differentiation
BMP2, BMP4, GLI3, WNT10B, LEF1, AXIN2, MSX2, BMPR2
 GO:0001649 8 / 137 14.7× 6.82e-8 8.79e-6 ✓ sig.
stem cell proliferation
KDF1, GLI3, TP63, AXIN2, FGFR1, IRF6
 GO:0072089 6 / 54 28.1× 6.97e-8 8.94e-6 ✓ sig.
skin development
EDA, KDF1, WNT10A, RIPK4, DSP, IRF6
 GO:0043588 6 / 55 27.5× 7.80e-8 9.76e-6 ✓ sig.
limb development
DKK1, GLI3, KREMEN1, IRF6, VPS54, BMPR2
 GO:0060173 6 / 56 27.1× 8.71e-8 1.07e-5 ✓ sig.
chondrocyte differentiation
BMP2, BMP4, GLI3, LTBP3, WNT10B, FGFR1
 GO:0002062 6 / 61 24.8× 1.47e-7 1.67e-5 ✓ sig.
stem cell differentiation
BMP4, MSX1, TP63, FGFR1, MSX2, BMPR2
 GO:0048863 6 / 63 24.1× 1.78e-7 1.96e-5 ✓ sig.
canonical Wnt signaling pathway
EDA, LRP6, WNT10A, DKK1, WNT10B, LEF1, AXIN2
 GO:0060070 7 / 105 16.8× 1.91e-7 2.08e-5 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Ectodermal dysplasia Hypohidrotic ectodermal dysplasia 0.143 5 5.85e-13 7.62e-12 ✓ sig.
Christ-siemens-touraine syndrome Ectodermal dysplasia 0.118 4 7.67e-11 8.18e-10 ✓ sig.
Christ-siemens-touraine syndrome X-linked hypohidrotic ectodermal dysplasia 0.333 2 8.44e-8 6.27e-7 ✓ sig.
Hypohidrotic ectodermal dysplasia Tooth agenesis 0.065 3 6.09e-7 3.92e-6 ✓ sig.
Ectodermal dysplasia Tooth agenesis 0.057 4 1.47e-6 8.88e-6 ✓ sig.
Christ-siemens-touraine syndrome Hypohidrotic ectodermal dysplasia 0.182 2 1.77e-6 1.05e-5 ✓ sig.
Anhidrotic ectodermal dysplasia X-linked hypohidrotic ectodermal dysplasia 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Craniofrontonasal dysplasia X-linked intellectual disability-cerebellar hypoplasia syndrome 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Anhidrotic ectodermal dysplasia Craniofrontonasal dysplasia 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Christ-siemens-touraine syndrome ectodermal dysplasia 10b, hypohidrotic/hair/tooth type, autosomal recessive 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Anhidrotic ectodermal dysplasia Christ-siemens-touraine syndrome 0.167 1 3.25e-4 7.58e-4 ✓ sig.
ectodermal dysplasia 10b, hypohidrotic/hair/tooth type, autosomal recessive Hypohidrotic ectodermal dysplasia 0.125 1 4.55e-4 9.55e-4 ✓ sig.
ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type Hypohidrotic ectodermal dysplasia 0.125 1 4.55e-4 9.55e-4 ✓ sig.
Craniofrontonasal dysplasia X-linked hypohidrotic ectodermal dysplasia 0.167 1 5.19e-4 1.04e-3 ✓ sig.
Anhidrotic ectodermal dysplasia Ectodermal dysplasia 0.030 1 2.08e-3 2.95e-3 ✓ sig.
Ectodermal dysplasia ectodermal dysplasia 10b, hypohidrotic/hair/tooth type, autosomal recessive 0.030 1 2.08e-3 2.95e-3 ✓ sig.
Ectodermal dysplasia ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type 0.030 1 2.08e-3 2.95e-3 ✓ sig.
Absence of fingerprints-congenital milia syndrome Ectodermal dysplasia 0.030 1 2.08e-3 2.95e-3 ✓ sig.
Anhidrotic ectodermal dysplasia Tooth agenesis 0.024 1 2.66e-3 3.58e-3 ✓ sig.
Tooth agenesis tooth agenesis, selective, 3 0.024 1 2.66e-3 3.58e-3 ✓ sig.
Tooth agenesis tooth agenesis, selective, 9 0.024 1 2.66e-3 3.58e-3 ✓ sig.
Ectodermal dysplasia X-linked hypohidrotic ectodermal dysplasia 0.029 1 4.15e-3 5.23e-3 ✓ sig.
Tooth agenesis X-linked hypohidrotic ectodermal dysplasia 0.023 1 5.32e-3 6.49e-3 ✓ sig.