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 158

9 diseases · 10 shared-gene connections
9 Diseases
46 Unique genes
0.116 Avg. similarity score
Erythropoietic protoporphyria Most-connected disease (5 links)
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Disease Searched: SRD5A3-congenital disorder of glycosylation 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 ⇵
Erythropoietic protoporphyria 5 5 6
Sideroblastic anemia 3 3 11
X-linked erythropoietic protoporphyria 3 3 1
X-linked sideroblastic anemia 3 3 4
Creutzfeldt-jakob disease 2 2 26
Bile duct disease 1 1 2
Bronchopneumonia 1 1 5
SRD5A3-congenital disorder of glycosylation 1 1 1
Spasticity with hyperglycinemia 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
ALAS2 4 / 9 Erythropoietic protoporphyria, Sideroblastic anemia, X-linked erythropoietic protoporphyria, X-linked sideroblastic anemia
ABCB7 2 / 9 Sideroblastic anemia, X-linked sideroblastic anemia
AREG 2 / 9 Creutzfeldt-jakob disease, Erythropoietic protoporphyria
BTC 2 / 9 Bronchopneumonia, Erythropoietic protoporphyria
EREG 2 / 9 Creutzfeldt-jakob disease, Erythropoietic protoporphyria
FECH 2 / 9 Bile duct disease, Erythropoietic protoporphyria
GLRX5 2 / 9 Sideroblastic anemia, Spasticity with hyperglycinemia
SLC25A38 2 / 9 Sideroblastic anemia, X-linked sideroblastic anemia
SRD5A3 2 / 9 Creutzfeldt-jakob disease, SRD5A3-congenital disorder of glycosylation
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 ⇵
Inhibition of Signaling by Overexpressed EGFR
BTC, AREG, EREG
 Reactome 3 / 8 97.9× 2.91e-6 1.30e-4 ✓ sig.
EGFR interacts with phospholipase C-gamma
BTC, AREG, EREG
 Reactome 3 / 9 87.0× 4.35e-6 1.81e-4 ✓ sig.
Signaling by EGFR
BTC, AREG, EREG
 Reactome 3 / 11 71.2× 8.49e-6 3.12e-4 ✓ sig.
GRB2 events in EGFR signaling
BTC, AREG, EREG
 Reactome 3 / 13 60.3× 1.46e-5 4.86e-4 ✓ sig.
SHC1 events in EGFR signaling
BTC, AREG, EREG
 Reactome 3 / 14 55.9× 1.86e-5 5.92e-4 ✓ sig.
GAB1 signalosome
BTC, AREG, EREG
 Reactome 3 / 17 46.1× 3.44e-5 9.84e-4 ✓ sig.
Estrogen-dependent nuclear events downstream of ESR-membrane signaling
BTC, AREG, EREG
 Reactome 3 / 23 34.1× 8.83e-5 2.10e-3 ✓ sig.
EGFR downregulation
BTC, AREG, EREG
 Reactome 3 / 31 25.3× 2.19e-4 4.30e-3 ✓ sig.
ErbB signaling pathway
BTC, CBLB, AREG, EREG
 KEGG 4 / 86 12.1× 3.18e-4 5.78e-3 ✓ sig.
ATF6 (ATF6-alpha) activates chaperone genes
ATF6, CALR
 Reactome 2 / 9 58.0× 5.08e-4 8.37e-3 ✓ sig.
PI3K events in ERBB4 signaling
BTC, EREG
 Reactome 2 / 10 52.2× 6.33e-4 9.93e-3 ✓ sig.
Mitochondrial iron-sulfur cluster biogenesis
GLRX5, HSCB
 Reactome 2 / 10 52.2× 6.33e-4 9.93e-3 ✓ sig.
Signaling by ERBB4
BTC, EREG
 Reactome 2 / 11 47.5× 7.72e-4 1.16e-2 ✓ sig.
ERBB2 Activates PTK6 Signaling
BTC, EREG
 Reactome 2 / 13 40.2× 1.09e-3 1.50e-2 ✓ sig.
SHC1 events in ERBB4 signaling
BTC, EREG
 Reactome 2 / 14 37.3× 1.27e-3 1.69e-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 ⇵
iron-sulfur cluster assembly
ABCB7, GLRX5, HSPA9, HSCB
 GO:0016226 4 / 27 60.2× 5.41e-7 5.12e-5 ✓ sig.
ERBB2-EGFR signaling pathway
BTC, AREG, EREG
 GO:0038134 3 / 8 152× 7.75e-7 6.88e-5 ✓ sig.
erythrocyte differentiation
ALAS2, HSPA9, SLC25A38, FECH
 GO:0030218 4 / 65 25.0× 1.95e-5 9.09e-4 ✓ sig.
heme biosynthetic process
ALAS2, SLC25A38, FECH
 GO:0006783 3 / 27 45.1× 3.92e-5 1.55e-3 ✓ sig.
ERBB4-ERBB4 signaling pathway
BTC, EREG
 GO:0038138 2 / 6 135× 8.84e-5 2.86e-3 ✓ sig.
heme B biosynthetic process
ALAS2, FECH
 GO:0006785 2 / 10 81.2× 2.63e-4 6.34e-3 ✓ sig.
intracellular oxygen homeostasis
ALAS2, SOD2
 GO:0032364 2 / 10 81.2× 2.63e-4 6.34e-3 ✓ sig.
[2Fe-2S] cluster assembly
GLRX5, HSCB
 GO:0044571 2 / 11 73.9× 3.21e-4 7.28e-3 ✓ sig.
synaptic vesicle docking
STX1A, UNC13C
 GO:0016081 2 / 13 62.5× 4.54e-4 9.28e-3 ✓ sig.
epidermal growth factor receptor signaling pathway
BTC, AREG, EREG
 GO:0007173 3 / 64 19.0× 5.24e-4 1.02e-2 ✓ sig.
intracellular iron ion homeostasis
ABCB7, ALAS2, GLRX5
 GO:0006879 3 / 71 17.2× 7.10e-4 1.25e-2 ✓ sig.
intracellular copper ion homeostasis
PRND, PRNP
 GO:0006878 2 / 18 45.1× 8.85e-4 1.45e-2 ✓ sig.
positive regulation of phosphorylation
AREG, EREG
 GO:0042327 2 / 20 40.6× 1.09e-3 1.65e-2 ✓ sig.
response to cadmium ion
SOD2, PRNP
 GO:0046686 2 / 21 38.7× 1.21e-3 1.75e-2 ✓ sig.
vesicle docking
STX1A, STX6
 GO:0048278 2 / 21 38.7× 1.21e-3 1.75e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Sideroblastic anemia X-linked sideroblastic anemia 0.231 3 1.08e-9 9.79e-9 ✓ sig.
Creutzfeldt-jakob disease Erythropoietic protoporphyria 0.065 2 4.10e-5 1.87e-4 ✓ sig.
X-linked erythropoietic protoporphyria X-linked sideroblastic anemia 0.200 1 2.60e-4 6.51e-4 ✓ sig.
Erythropoietic protoporphyria X-linked erythropoietic protoporphyria 0.143 1 3.90e-4 8.67e-4 ✓ sig.
Sideroblastic anemia X-linked erythropoietic protoporphyria 0.083 1 7.14e-4 1.34e-3 ✓ sig.
Sideroblastic anemia Spasticity with hyperglycinemia 0.083 1 7.14e-4 1.34e-3 ✓ sig.
Bile duct disease Erythropoietic protoporphyria 0.125 1 7.79e-4 1.41e-3 ✓ sig.
Erythropoietic protoporphyria X-linked sideroblastic anemia 0.100 1 1.56e-3 2.38e-3 ✓ sig.
Creutzfeldt-jakob disease SRD5A3-congenital disorder of glycosylation 0.037 1 1.69e-3 2.53e-3 ✓ sig.
Bronchopneumonia Erythropoietic protoporphyria 0.091 1 1.95e-3 2.83e-3 ✓ sig.