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 188

8 diseases · 15 shared-gene connections
8 Diseases
8 Unique genes
0.265 Avg. similarity score
Ferroxidase deficiency Most-connected disease (6 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 ⇵
Ferroxidase deficiency 6 6 3
Iron overload 6 6 7
Apoceruloplasmin deficiency 5 5 2
Aceruloplasminemia 4 4 1
Hemosiderosis 4 4 1
hemochromatosis type 4 3 3 1
hermansky-pudlak syndrome 3 1 1 1
iron overload, susceptibility to 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
CP 5 / 8 Aceruloplasminemia, Apoceruloplasmin deficiency, Ferroxidase deficiency, Hemosiderosis and 1 more
SLC40A1 4 / 8 Apoceruloplasmin deficiency, Ferroxidase deficiency, hemochromatosis type 4, Iron overload
BMP6 2 / 8 Iron overload, iron overload, susceptibility to
HPS3 2 / 8 Ferroxidase deficiency, hermansky-pudlak syndrome 3
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 ⇵
Iron uptake and transport
CP, SLC40A1, FTH1, TF
 Reactome 4 / 28 214× 1.64e-9 1.73e-7 ✓ sig.
Ferroptosis
CP, SLC40A1, FTH1, TF
 KEGG 4 / 42 143× 8.95e-9 7.92e-7 ✓ sig.
Defective SLC40A1 causes hemochromatosis 4 (HFE4) (macrophages)
CP, SLC40A1
 Reactome 2 / 2 1,501× 3.88e-7 2.15e-5 ✓ sig.
Defective CP causes aceruloplasminemia (ACERULOP)
CP, SLC40A1
 Reactome 2 / 2 1,501× 3.88e-7 2.15e-5 ✓ sig.
Mineral absorption
SLC40A1, FTH1, TF
 KEGG 3 / 61 73.8× 6.86e-6 2.45e-4 ✓ sig.
Metal ion SLC transporters
CP, SLC40A1
 Reactome 2 / 9 334× 1.39e-5 4.42e-4 ✓ sig.
TGF-beta signaling pathway
BMP6, HAMP, TF
 KEGG 3 / 108 41.7× 3.83e-5 1.03e-3 ✓ sig.
Porphyrin metabolism
CP, FTH1
 KEGG 2 / 46 65.3× 3.96e-4 6.66e-3 ✓ sig.
Defective SLC40A1 causes hemochromatosis 4 (HFE4) (duodenum)
SLC40A1
 Reactome 1 / 2 751× 1.33e-3 1.68e-2 ✓ sig.
Post-translational protein phosphorylation
CP, TF
 Reactome 2 / 108 27.8× 2.17e-3 2.42e-2 ✓ sig.
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
CP, TF
 Reactome 2 / 125 24.0× 2.89e-3 3.00e-2 ✓ sig.
Hormone signaling
SLC40A1, HAMP
 KEGG 2 / 219 13.7× 8.62e-3 6.28e-2
Transferrin endocytosis and recycling
TF
 Reactome 1 / 31 48.4× 2.05e-2 1.04e-1
Ovarian steroidogenesis
BMP6
 KEGG 1 / 52 28.9× 3.41e-2 1.39e-1
Golgi Associated Vesicle Biogenesis
FTH1
 Reactome 1 / 56 26.8× 3.67e-2 1.45e-1

Enriched GO Terms (Biological Process, a second line of biological evidence)

GO term ⇵ GO ID ⇵ Overlap genes ⇵ Fold enrichment ⇵ P-value ⇵ FDR q-value ⇵
intracellular iron ion homeostasis
CP, SLC40A1, BMP6, FTH1, HAMP, TF
 GO:0006879 6 / 71 197× 6.75e-14 3.81e-11 ✓ sig.
iron ion export across plasma membrane
SLC40A1, HAMP, TF
 GO:1903988 3 / 3 2,336× 5.15e-11 1.59e-8 ✓ sig.
multicellular organismal-level iron ion homeostasis
SLC40A1, BMP6, HAMP, TF
 GO:0060586 4 / 28 334× 2.81e-10 7.21e-8 ✓ sig.
iron ion transport
SLC40A1, FTH1, TF
 GO:0006826 3 / 31 226× 2.30e-7 2.44e-5 ✓ sig.
cellular response to iron ion
BMP6, TF
 GO:0071281 2 / 7 667× 3.36e-6 2.19e-4 ✓ sig.
response to iron ion
BMP6, HAMP
 GO:0010039 2 / 18 260× 2.45e-5 1.05e-3 ✓ sig.
negative regulation of iron ion transmembrane transport
HAMP
 GO:0034760 1 / 1 2,336× 4.28e-4 8.59e-3 ✓ sig.
negative regulation of iron export across plasma membrane
HAMP
 GO:1904039 1 / 1 2,336× 4.28e-4 8.59e-3 ✓ sig.
negative regulation of intestinal absorption
HAMP
 GO:1904479 1 / 1 2,336× 4.28e-4 8.59e-3 ✓ sig.
spleen trabecula formation
SLC40A1
 GO:0060345 1 / 1 2,336× 4.28e-4 8.59e-3 ✓ sig.
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
HAMP, TF
 GO:0032436 2 / 79 59.1× 4.86e-4 9.37e-3 ✓ sig.
gamma-aminobutyric acid secretion, neurotransmission
BEST1
 GO:0061534 1 / 2 1,168× 8.56e-4 1.36e-2 ✓ sig.
negative regulation of adherens junction organization
BMP6
 GO:1903392 1 / 2 1,168× 8.56e-4 1.36e-2 ✓ sig.
immune response
BMP6, FTH1, HAMP
 GO:0006955 3 / 543 12.9× 1.23e-3 1.71e-2 ✓ sig.
positive regulation of aldosterone biosynthetic process
BMP6
 GO:0032349 1 / 3 779× 1.28e-3 1.75e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Apoceruloplasmin deficiency Ferroxidase deficiency 0.500 2 2.53e-8 2.03e-7 ✓ sig.
Apoceruloplasmin deficiency Iron overload 0.250 2 1.77e-7 1.25e-6 ✓ sig.
Ferroxidase deficiency Iron overload 0.222 2 5.31e-7 3.46e-6 ✓ sig.
Aceruloplasminemia Hemosiderosis 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Aceruloplasminemia Apoceruloplasmin deficiency 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Apoceruloplasmin deficiency Hemosiderosis 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Apoceruloplasmin deficiency hemochromatosis type 4 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Aceruloplasminemia Ferroxidase deficiency 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Ferroxidase deficiency Hemosiderosis 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Ferroxidase deficiency hemochromatosis type 4 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Ferroxidase deficiency hermansky-pudlak syndrome 3 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Aceruloplasminemia Iron overload 0.125 1 4.55e-4 9.55e-4 ✓ sig.
hemochromatosis type 4 Iron overload 0.125 1 4.55e-4 9.55e-4 ✓ sig.
Hemosiderosis Iron overload 0.125 1 4.55e-4 9.55e-4 ✓ sig.
Iron overload iron overload, susceptibility to 0.125 1 4.55e-4 9.55e-4 ✓ sig.