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 244

8 diseases · 20 shared-gene connections
8 Diseases
32 Unique genes
0.366 Avg. similarity score
Holoprosencephaly Most-connected disease (6 links)
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Disease Searched: Holoprosencephaly-hypokinesia-congenital contractures syndrome 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 ⇵
Holoprosencephaly 6 6 30
Microform holoprosencephaly 6 6 16
Semilobar holoprosencephaly 6 6 18
Septopreoptic holoprosencephaly 6 6 15
Syntelencephaly 6 6 15
Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures 5 5 1
Holoprosencephaly 5 4 4 1
Holoprosencephaly-hypokinesia-congenital contractures syndrome 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
DLL1 6 / 8 Holoprosencephaly, Microform holoprosencephaly, Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures, Semilobar holoprosencephaly and 2 more
ZIC2 6 / 8 Holoprosencephaly, Holoprosencephaly 5, Microform holoprosencephaly, Semilobar holoprosencephaly and 2 more
CDON 5 / 8 Holoprosencephaly, Microform holoprosencephaly, Semilobar holoprosencephaly, Septopreoptic holoprosencephaly and 1 more
CRIPTO 5 / 8 Holoprosencephaly, Microform holoprosencephaly, Semilobar holoprosencephaly, Septopreoptic holoprosencephaly and 1 more
DISP1 5 / 8 Holoprosencephaly, Microform holoprosencephaly, Semilobar holoprosencephaly, Septopreoptic holoprosencephaly and 1 more
FGF8 5 / 8 Holoprosencephaly, Microform holoprosencephaly, Semilobar holoprosencephaly, Septopreoptic holoprosencephaly and 1 more
FOXH1 5 / 8 Holoprosencephaly, Microform holoprosencephaly, Semilobar holoprosencephaly, Septopreoptic holoprosencephaly and 1 more
GAS1 5 / 8 Holoprosencephaly, Microform holoprosencephaly, Semilobar holoprosencephaly, Septopreoptic holoprosencephaly and 1 more
GLI2 5 / 8 Holoprosencephaly, Microform holoprosencephaly, Semilobar holoprosencephaly, Septopreoptic holoprosencephaly and 1 more
NODAL 5 / 8 Holoprosencephaly, Microform holoprosencephaly, Semilobar holoprosencephaly, Septopreoptic holoprosencephaly and 1 more
PTCH1 5 / 8 Holoprosencephaly, Microform holoprosencephaly, Semilobar holoprosencephaly, Septopreoptic holoprosencephaly and 1 more
SHH 5 / 8 Holoprosencephaly, Microform holoprosencephaly, Semilobar holoprosencephaly, Septopreoptic holoprosencephaly and 1 more
SIX3 5 / 8 Holoprosencephaly, Microform holoprosencephaly, Semilobar holoprosencephaly, Septopreoptic holoprosencephaly and 1 more
TGIF1 5 / 8 Holoprosencephaly, Microform holoprosencephaly, Semilobar holoprosencephaly, Septopreoptic holoprosencephaly and 1 more
STIL 4 / 8 Holoprosencephaly, Semilobar holoprosencephaly, Septopreoptic holoprosencephaly, Syntelencephaly
FGFR1 3 / 8 Holoprosencephaly, Microform holoprosencephaly, Semilobar holoprosencephaly
GPKOW 2 / 8 Holoprosencephaly, Holoprosencephaly-hypokinesia-congenital contractures syndrome
STAG2 2 / 8 Holoprosencephaly, Semilobar holoprosencephaly
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 ⇵
Hedgehog signaling pathway
BOC, CDON, DISP1, GAS1, GLI2, PTCH1, SHH, SUFU
 KEGG 8 / 56 53.6× 1.28e-12 2.38e-10 ✓ sig.
Activation of SMO
BOC, CDON, GAS1, PTCH1, SHH
 Reactome 5 / 18 104× 8.09e-10 7.68e-8 ✓ sig.
Ligand-receptor interactions
CDON, GAS1, PTCH1, SHH
 Reactome 4 / 7 214× 1.44e-9 1.30e-7 ✓ sig.
Basal cell carcinoma
GLI2, PTCH1, SHH, SUFU
 KEGG 4 / 63 23.8× 2.21e-5 5.67e-4 ✓ sig.
Pathways in cancer
DLL1, FGF8, FGFR1, GLI2, LAMA5, PTCH1, SHH, SUFU
 KEGG 8 / 533 5.6× 5.84e-5 1.23e-3 ✓ sig.
Cohesin Loading onto Chromatin
STAG2, SMC1A
 Reactome 2 / 10 75.1× 3.05e-4 4.57e-3 ✓ sig.
Establishment of Sister Chromatid Cohesion
STAG2, SMC1A
 Reactome 2 / 11 68.2× 3.73e-4 5.32e-3 ✓ sig.
Signaling by activated point mutants of FGFR1
FGF8, FGFR1
 Reactome 2 / 11 68.2× 3.73e-4 5.32e-3 ✓ sig.
Hedgehog 'off' state
GLI2, PTCH1, SUFU
 Reactome 3 / 56 20.1× 4.33e-4 5.97e-3 ✓ sig.
FGFR1c ligand binding and activation
FGF8, FGFR1
 Reactome 2 / 12 62.6× 4.46e-4 6.11e-3 ✓ sig.
Phospholipase C-mediated cascade: FGFR1
FGF8, FGFR1
 Reactome 2 / 16 46.9× 8.06e-4 9.61e-3 ✓ sig.
Hedgehog 'on' state
GLI2, PTCH1, SUFU
 Reactome 3 / 70 16.1× 8.33e-4 9.86e-3 ✓ sig.
Downstream signaling of activated FGFR1
FGF8, FGFR1
 Reactome 2 / 18 41.7× 1.02e-3 1.15e-2 ✓ sig.
PI-3K cascade:FGFR1
FGF8, FGFR1
 Reactome 2 / 21 35.7× 1.40e-3 1.46e-2 ✓ sig.
SHC-mediated cascade:FGFR1
FGF8, FGFR1
 Reactome 2 / 21 35.7× 1.40e-3 1.46e-2 ✓ 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 ⇵
determination of left/right symmetry
DISP1, DLL1, FGF8, FOXH1, NODAL, SHH, STIL, TGIF1, SUFU
 GO:0007368 9 / 83 63.3× 1.11e-14 7.54e-12 ✓ sig.
heart looping
DLL1, FGF8, FOXH1, NODAL, SHH, STIL, SUFU
 GO:0001947 7 / 64 63.9× 1.24e-11 4.67e-9 ✓ sig.
branching involved in salivary gland morphogenesis
FGF8, FGFR1, LAMA5, SHH
 GO:0060445 4 / 12 195× 3.47e-9 6.93e-7 ✓ sig.
smoothened signaling pathway
CDON, DISP1, GLI2, SHH, STIL, SUFU
 GO:0007224 6 / 94 37.3× 1.12e-8 1.95e-6 ✓ sig.
dorsal/ventral pattern formation
DISP1, FGF8, PTCH1, SHH, TGIF1
 GO:0009953 5 / 47 62.1× 1.55e-8 2.58e-6 ✓ sig.
lung development
FGF8, FGFR1, GLI2, LAMA5, NODAL, SHH
 GO:0030324 6 / 108 32.4× 2.60e-8 4.06e-6 ✓ sig.
spinal cord dorsal/ventral patterning
GLI2, SHH, SUFU
 GO:0021513 3 / 8 219× 2.54e-7 2.76e-5 ✓ sig.
determination of left/right asymmetry in lateral mesoderm
FOXH1, NODAL, SHH
 GO:0003140 3 / 10 175× 5.43e-7 5.23e-5 ✓ sig.
branching involved in ureteric bud morphogenesis
FGF8, LAMA5, PTCH1, SHH
 GO:0001658 4 / 45 51.9× 1.00e-6 8.62e-5 ✓ sig.
nodal signaling pathway
FOXH1, NODAL, TGIF1
 GO:0038092 3 / 15 117× 2.05e-6 1.54e-4 ✓ sig.
stem cell proliferation
FGF8, FGFR1, PTCH1, SHH
 GO:0072089 4 / 54 43.3× 2.11e-6 1.58e-4 ✓ sig.
negative regulation of transcription by RNA polymerase II
CNOT1, FGFR1, FOXH1, GLI2, NODAL, PTCH1, SHH, TGIF1, NSD1, SUFU
 GO:0000122 10 / 1,002 5.8× 4.11e-6 2.71e-4 ✓ sig.
cell fate commitment
FGF8, GAS1, NODAL, SHH
 GO:0045165 4 / 75 31.1× 7.90e-6 4.55e-4 ✓ sig.
ventral midline development
GLI2, SHH
 GO:0007418 2 / 3 389× 8.51e-6 4.80e-4 ✓ sig.
smoothened signaling pathway involved in ventral spinal cord interneuron specification
GLI2, SUFU
 GO:0021775 2 / 3 389× 8.51e-6 4.80e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Septopreoptic holoprosencephaly Syntelencephaly 0.938 15 1.86e-51 5.08e-50 ✓ sig.
Semilobar holoprosencephaly Septopreoptic holoprosencephaly 0.789 15 1.52e-48 4.00e-47 ✓ sig.
Semilobar holoprosencephaly Syntelencephaly 0.789 15 1.52e-48 4.00e-47 ✓ sig.
Holoprosencephaly Semilobar holoprosencephaly 0.531 17 4.55e-48 1.19e-46 ✓ sig.
Microform holoprosencephaly Semilobar holoprosencephaly 0.750 15 2.43e-47 6.31e-46 ✓ sig.
Microform holoprosencephaly Septopreoptic holoprosencephaly 0.778 14 3.45e-45 8.69e-44 ✓ sig.
Microform holoprosencephaly Syntelencephaly 0.778 14 3.45e-45 8.69e-44 ✓ sig.
Holoprosencephaly Septopreoptic holoprosencephaly 0.484 15 2.89e-43 7.05e-42 ✓ sig.
Holoprosencephaly Syntelencephaly 0.484 15 2.89e-43 7.05e-42 ✓ sig.
Holoprosencephaly Microform holoprosencephaly 0.469 15 4.61e-42 1.11e-40 ✓ sig.
Holoprosencephaly 5 Septopreoptic holoprosencephaly 0.063 1 9.68e-4 1.50e-3 ✓ sig.
Holoprosencephaly 5 Syntelencephaly 0.063 1 9.68e-4 1.50e-3 ✓ sig.
Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures Syntelencephaly 0.063 1 9.68e-4 1.50e-3 ✓ sig.
Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures Septopreoptic holoprosencephaly 0.063 1 9.68e-4 1.50e-3 ✓ sig.
Holoprosencephaly 5 Microform holoprosencephaly 0.059 1 1.03e-3 1.57e-3 ✓ sig.
Microform holoprosencephaly Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures 0.059 1 1.03e-3 1.57e-3 ✓ sig.
Holoprosencephaly 5 Semilobar holoprosencephaly 0.053 1 1.16e-3 1.73e-3 ✓ sig.
Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures Semilobar holoprosencephaly 0.053 1 1.16e-3 1.73e-3 ✓ sig.
Holoprosencephaly Holoprosencephaly-hypokinesia-congenital contractures syndrome 0.032 1 1.94e-3 2.65e-3 ✓ sig.
Holoprosencephaly Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures 0.032 1 1.94e-3 2.65e-3 ✓ sig.