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 148

9 diseases · 18 shared-gene connections
9 Diseases
51 Unique genes
0.139 Avg. similarity score
Hemochromatosis Most-connected disease (7 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 ⇵
Hemochromatosis 7 7 14
Digenic hemochromatosis 6 6 4
Beta thalassemia 5 5 21
Hereditary hemochromatosis 5 5 7
hemochromatosis type 2B 4 4 1
hemochromatosis type 3 4 4 1
Iron metabolism disorder 2 2 22
hemochromatosis type 2A 2 2 1
lessel-kreienkamp syndrome 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
HAMP 5 / 9 Beta thalassemia, Digenic hemochromatosis, Hemochromatosis, hemochromatosis type 2B and 1 more
HFE 5 / 9 Beta thalassemia, Digenic hemochromatosis, Hemochromatosis, Hereditary hemochromatosis and 1 more
TFR2 5 / 9 Beta thalassemia, Digenic hemochromatosis, Hemochromatosis, hemochromatosis type 3 and 1 more
HJV 3 / 9 Digenic hemochromatosis, Hemochromatosis, hemochromatosis type 2A
AGO2 2 / 9 Iron metabolism disorder, lessel-kreienkamp syndrome
BMP2 2 / 9 Hemochromatosis, Iron metabolism disorder
CP 2 / 9 Hemochromatosis, Iron metabolism disorder
FTH1 2 / 9 Hemochromatosis, Iron metabolism disorder
SLC40A1 2 / 9 Hemochromatosis, Hereditary hemochromatosis
TFRC 2 / 9 Beta thalassemia, Iron metabolism disorder
TNF 2 / 9 Beta thalassemia, Hemochromatosis
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
LCN2, CP, SLC11A2, SLC40A1, FTH1, CYBRD1, HEPH, TF, FTL, HMOX1
 Reactome 10 / 28 84.1× 9.25e-18 5.01e-15 ✓ sig.
Ferroptosis
TFRC, CP, SLC11A2, SLC40A1, FTH1, TF, FTL, HMOX1
 KEGG 8 / 42 44.9× 6.30e-12 1.17e-9 ✓ sig.
Mineral absorption
SLC11A2, SLC40A1, FTH1, CYBRD1, HEPH, TF, FTL, HMOX1
 KEGG 8 / 61 30.9× 1.48e-10 2.06e-8 ✓ sig.
TGF-beta signaling pathway
HAMP, HFE, TFR2, TFRC, TNF, HJV, BMP2, BMP6, TF
 KEGG 9 / 108 19.6× 6.09e-10 7.18e-8 ✓ sig.
Porphyrin metabolism
CP, ALAS2, FTH1, HEPH, FTL, HMOX1
 KEGG 6 / 46 30.7× 3.56e-8 2.65e-6 ✓ sig.
Metal ion SLC transporters
CP, SLC11A2, SLC40A1, HEPH
 Reactome 4 / 9 105× 3.58e-8 2.66e-6 ✓ sig.
Pyrimidine biosynthesis
CAD, DHODH, UMPS
 Reactome 3 / 3 235× 7.21e-8 4.92e-6 ✓ sig.
Transferrin endocytosis and recycling
HFE, TFR2, TFRC, TF
 Reactome 4 / 31 30.4× 8.34e-6 2.88e-4 ✓ sig.
Defective SLC40A1 causes hemochromatosis 4 (HFE4) (macrophages)
CP, SLC40A1
 Reactome 2 / 2 235× 1.77e-5 5.40e-4 ✓ sig.
Defective CP causes aceruloplasminemia (ACERULOP)
CP, SLC40A1
 Reactome 2 / 2 235× 1.77e-5 5.40e-4 ✓ sig.
Defective SLC40A1 causes hemochromatosis 4 (HFE4) (duodenum)
SLC40A1, HEPH
 Reactome 2 / 2 235× 1.77e-5 5.40e-4 ✓ sig.
Scavenging of heme from plasma
HBB, HBA2, HP
 Reactome 3 / 13 54.3× 2.00e-5 5.99e-4 ✓ sig.
Hormone signaling
EPO, GH1, HAMP, SLC40A1, HEPH, JAK2
 KEGG 6 / 219 6.5× 3.12e-4 5.53e-3 ✓ sig.
African trypanosomiasis
HBB, HBA2, TNF
 KEGG 3 / 37 19.1× 5.06e-4 8.04e-3 ✓ sig.
Erythrocytes take up oxygen and release carbon dioxide
HBB, HBA2
 Reactome 2 / 9 52.3× 6.24e-4 9.49e-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 ⇵
intracellular iron ion homeostasis
HAMP, HFE, TFR2, TFRC, HJV, CP, ALAS2, BMP6, SLC11A2, SLC40A1, FTH1, CYBRD1
 GO:0006879 16 / 71 82.6× 1.98e-27 8.47e-24 ✓ sig.
multicellular organismal-level iron ion homeostasis
HAMP, HFE, TFR2, TFRC, HJV, BMP6, SLC11A2, SLC40A1, CYBRD1, HEPH, TF, TMPRSS6
 GO:0060586 13 / 28 170× 3.20e-27 1.33e-23 ✓ sig.
iron ion transport
HFE, LCN2, TFR2, TFRC, SLC11A2, SLC40A1, FTH1, HEPH, TF, FTL
 GO:0006826 10 / 31 118× 3.81e-19 5.46e-16 ✓ sig.
response to iron ion
HAMP, HFE, TFR2, TFRC, BMP6, SLC11A2, CYBRD1
 GO:0010039 7 / 18 142× 2.28e-14 1.39e-11 ✓ sig.
cellular response to iron ion
HFE, TFR2, BMP6, TF
 GO:0071281 4 / 7 209× 1.71e-9 3.61e-7 ✓ sig.
'de novo' UMP biosynthetic process
CAD, DHODH, UMPS
 GO:0044205 3 / 3 366× 1.92e-8 3.01e-6 ✓ sig.
iron ion export across plasma membrane
HAMP, SLC40A1, TF
 GO:1903988 3 / 3 366× 1.92e-8 3.01e-6 ✓ sig.
erythrocyte development
HBB, GATA1, HBA2, ALAS2, SLC11A2
 GO:0048821 5 / 32 57.3× 2.36e-8 3.60e-6 ✓ sig.
response to hydrogen peroxide
HBB, COL1A1, HBA2, HP, HMOX1
 GO:0042542 5 / 39 47.0× 6.65e-8 8.62e-6 ✓ sig.
UDP biosynthetic process
CAD, DHODH, UMPS
 GO:0006225 3 / 5 220× 1.91e-7 2.08e-5 ✓ sig.
'de novo' pyrimidine nucleobase biosynthetic process
CAD, DHODH, UMPS
 GO:0006207 3 / 6 183× 3.81e-7 3.72e-5 ✓ sig.
cellular oxidant detoxification
HBB, GSTT1, HBA2, CP, HP
 GO:0098869 5 / 66 27.8× 9.76e-7 8.13e-5 ✓ sig.
pyrimidine nucleotide biosynthetic process
CAD, DHODH, UMPS
 GO:0006221 3 / 9 122× 1.59e-6 1.20e-4 ✓ sig.
acute-phase response
EPO, LCN2, TFRC, HP
 GO:0006953 4 / 37 39.6× 3.04e-6 2.02e-4 ✓ sig.
transferrin transport
HFE, TFR2, TFRC
 GO:0033572 3 / 11 99.9× 3.11e-6 2.06e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Digenic hemochromatosis Hemochromatosis 0.267 4 4.28e-13 5.66e-12 ✓ sig.
Hemochromatosis Hereditary hemochromatosis 0.222 4 1.49e-11 1.72e-10 ✓ sig.
Digenic hemochromatosis Hereditary hemochromatosis 0.333 3 2.30e-10 2.34e-9 ✓ sig.
Beta thalassemia Hemochromatosis 0.125 4 2.54e-9 2.32e-8 ✓ sig.
Hemochromatosis Iron metabolism disorder 0.121 4 3.10e-9 2.82e-8 ✓ sig.
Beta thalassemia Digenic hemochromatosis 0.130 3 8.74e-9 7.44e-8 ✓ sig.
Beta thalassemia Hereditary hemochromatosis 0.115 3 7.62e-8 5.74e-7 ✓ sig.
Digenic hemochromatosis hemochromatosis type 3 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Digenic hemochromatosis hemochromatosis type 2B 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Digenic hemochromatosis hemochromatosis type 2A 0.200 1 2.60e-4 6.40e-4 ✓ sig.
hemochromatosis type 2B Hereditary hemochromatosis 0.125 1 4.55e-4 9.55e-4 ✓ sig.
hemochromatosis type 3 Hereditary hemochromatosis 0.125 1 4.55e-4 9.55e-4 ✓ sig.
Hemochromatosis hemochromatosis type 2A 0.067 1 9.09e-4 1.56e-3 ✓ sig.
Hemochromatosis hemochromatosis type 3 0.067 1 9.09e-4 1.56e-3 ✓ sig.
Hemochromatosis hemochromatosis type 2B 0.067 1 9.09e-4 1.56e-3 ✓ sig.
Beta thalassemia hemochromatosis type 2B 0.045 1 1.36e-3 2.13e-3 ✓ sig.
Beta thalassemia hemochromatosis type 3 0.045 1 1.36e-3 2.13e-3 ✓ sig.
Iron metabolism disorder lessel-kreienkamp syndrome 0.043 1 1.43e-3 2.21e-3 ✓ sig.