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 95

11 diseases · 19 shared-gene connections
11 Diseases
34 Unique genes
0.129 Avg. similarity score
Iron deficiency anemia Most-connected disease (8 links)
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Disease Searched: Hypochromic microcytic anemia 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 ⇵
Iron deficiency anemia 8 8 10
Iron metabolism disorder 5 5 22
Microcytic anemia 5 5 4
Hypochromic microcytic anemia 4 4 5
IRIDA syndrome 4 4 1
Iron-refractory iron deficiency anemia 4 4 2
Hypochromic anemia 3 3 1
TFRC-related combined immunodeficiency 2 2 1
Hyperthermia 1 1 1
Hypochromic sideroblastic anemia 1 1 1
lessel-kreienkamp syndrome 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
TMPRSS6 5 / 11 IRIDA syndrome, Iron deficiency anemia, Iron metabolism disorder, Iron-refractory iron deficiency anemia and 1 more
SLC11A2 4 / 11 Hypochromic anemia, Hypochromic microcytic anemia, Iron deficiency anemia, Microcytic anemia
TFRC 3 / 11 Iron deficiency anemia, Iron metabolism disorder, TFRC-related combined immunodeficiency
AGO2 2 / 11 Iron metabolism disorder, lessel-kreienkamp syndrome
GPX1 2 / 11 Hyperthermia, Iron deficiency anemia
HFE 2 / 11 Iron deficiency anemia, Iron metabolism disorder
STEAP3 2 / 11 Hypochromic microcytic anemia, Hypochromic sideroblastic anemia
TF 2 / 11 Hypochromic microcytic anemia, Iron deficiency anemia
TNF 2 / 11 Hypochromic microcytic anemia, Iron deficiency anemia
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 ⇵
Ferroptosis
TF, SLC11A2, STEAP3, TFRC, CP, FTH1, FTL, HMOX1
 KEGG 8 / 42 67.3× 1.87e-13 4.36e-11 ✓ sig.
Iron uptake and transport
TF, SLC11A2, CP, FTH1, FTL, HMOX1
 Reactome 6 / 28 75.7× 1.16e-10 1.57e-8 ✓ sig.
Mineral absorption
TF, SLC11A2, FTH1, FTL, HMOX1
 KEGG 5 / 61 29.0× 7.11e-7 3.62e-5 ✓ sig.
Transferrin endocytosis and recycling
TF, STEAP3, TFRC, HFE
 Reactome 4 / 31 45.6× 1.60e-6 7.27e-5 ✓ sig.
Porphyrin metabolism
CP, FTH1, FTL, HMOX1
 KEGG 4 / 46 30.7× 8.03e-6 2.87e-4 ✓ sig.
TGF-beta signaling pathway
TF, TNF, TFRC, BMP2, HFE
 KEGG 5 / 108 16.4× 1.21e-5 4.00e-4 ✓ sig.
Metal ion SLC transporters
SLC11A2, CP
 Reactome 2 / 9 78.5× 2.77e-4 5.10e-3 ✓ sig.
Golgi Associated Vesicle Biogenesis
TFRC, FTH1, FTL
 Reactome 3 / 56 18.9× 5.19e-4 8.36e-3 ✓ sig.
Necroptosis
TNF, JAK2, FTH1, FTL
 KEGG 4 / 159 8.9× 1.01e-3 1.40e-2 ✓ sig.
Hematopoietic cell lineage
TNF, TFRC, ITGA2
 KEGG 3 / 100 10.6× 2.78e-3 2.97e-2 ✓ sig.
Defective SLC11A2 causes hypochromic microcytic anemia, with iron overload 1 (AHMIO1)
SLC11A2
 Reactome 1 / 1 353× 2.83e-3 3.00e-2 ✓ sig.
Pre-NOTCH Transcription and Translation
AGO2, E2F3
 Reactome 2 / 31 22.8× 3.44e-3 3.44e-2 ✓ sig.
Interleukin-4 and Interleukin-13 signaling
TNF, JAK2, HMOX1
 Reactome 3 / 108 9.8× 3.46e-3 3.45e-2 ✓ sig.
HIF-1 signaling pathway
TF, TFRC, HMOX1
 KEGG 3 / 110 9.6× 3.64e-3 3.58e-2 ✓ sig.
Detoxification of Reactive Oxygen Species
SOD1, GPX1
 Reactome 2 / 34 20.8× 4.12e-3 3.92e-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 ⇵
intracellular iron ion homeostasis
TF, SLC11A2, SOD1, TFRC, TMPRSS6, CP, FTH1, FTL, HFE, HMOX1
 GO:0006879 10 / 71 77.4× 3.95e-17 3.84e-14 ✓ sig.
iron ion transport
TF, SLC11A2, STEAP3, TFRC, FTH1, FTL, HFE
 GO:0006826 7 / 31 124× 8.70e-14 4.75e-11 ✓ sig.
multicellular organismal-level iron ion homeostasis
TF, SLC11A2, TFRC, TMPRSS6, HFE, HMOX1
 GO:0060586 6 / 28 118× 8.33e-12 3.10e-9 ✓ sig.
osteoclast differentiation
TF, TNF, TFRC, BMP2
 GO:0030316 4 / 49 44.9× 1.83e-6 1.36e-4 ✓ sig.
response to iron ion
SLC11A2, TFRC, HFE
 GO:0010039 3 / 18 91.6× 4.41e-6 2.77e-4 ✓ sig.
response to hypoxia
SLC11A2, TNF, TFRC, BMP2, ITGA2
 GO:0001666 5 / 176 15.6× 1.56e-5 7.51e-4 ✓ sig.
collagen-activated signaling pathway
JAK2, ITGA2
 GO:0038065 2 / 6 183× 4.80e-5 1.77e-3 ✓ sig.
response to hydrogen peroxide
SOD1, GPX1, HMOX1
 GO:0042542 3 / 39 42.3× 4.81e-5 1.78e-3 ✓ sig.
positive regulation of SMAD protein signal transduction
JAK2, BMP2, HFE
 GO:0060391 3 / 42 39.3× 6.02e-5 2.10e-3 ✓ sig.
cellular response to iron ion
TF, HFE
 GO:0071281 2 / 7 157× 6.71e-5 2.29e-3 ✓ sig.
negative regulation of vascular wound healing
TNF, TAFA5
 GO:0061044 2 / 8 137× 8.94e-5 2.85e-3 ✓ sig.
positive regulation of smooth muscle cell proliferation
TNF, HMOX1, ITGA2
 GO:0048661 3 / 52 31.7× 1.14e-4 3.41e-3 ✓ sig.
response to hydroperoxide
GPX1, JAK2
 GO:0033194 2 / 9 122× 1.15e-4 3.42e-3 ✓ sig.
response to oxidative stress
SOD1, GPX1, JAK2, HMOX1
 GO:0006979 4 / 146 15.1× 1.38e-4 3.93e-3 ✓ sig.
transferrin transport
TFRC, HFE
 GO:0033572 2 / 11 99.9× 1.75e-4 4.69e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hypochromic microcytic anemia Iron deficiency anemia 0.231 3 1.97e-9 1.74e-8 ✓ sig.
Iron deficiency anemia Iron metabolism disorder 0.100 3 3.02e-7 1.96e-6 ✓ sig.
Iron deficiency anemia Microcytic anemia 0.154 2 2.28e-6 1.26e-5 ✓ sig.
IRIDA syndrome Iron-refractory iron deficiency anemia 0.333 1 1.30e-4 3.91e-4 ✓ sig.
Hypochromic anemia Microcytic anemia 0.200 1 2.60e-4 6.48e-4 ✓ sig.
IRIDA syndrome Microcytic anemia 0.200 1 2.60e-4 6.48e-4 ✓ sig.
Hypochromic anemia Hypochromic microcytic anemia 0.167 1 3.25e-4 7.68e-4 ✓ sig.
Hypochromic microcytic anemia Hypochromic sideroblastic anemia 0.167 1 3.25e-4 7.68e-4 ✓ sig.
Iron-refractory iron deficiency anemia Microcytic anemia 0.167 1 5.19e-4 1.06e-3 ✓ sig.
Hypochromic anemia Iron deficiency anemia 0.091 1 6.49e-4 1.24e-3 ✓ sig.
IRIDA syndrome Iron deficiency anemia 0.091 1 6.49e-4 1.24e-3 ✓ sig.
Hyperthermia Iron deficiency anemia 0.091 1 6.49e-4 1.24e-3 ✓ sig.
Iron deficiency anemia TFRC-related combined immunodeficiency 0.091 1 6.49e-4 1.24e-3 ✓ sig.
Hypochromic microcytic anemia Microcytic anemia 0.111 1 1.30e-3 2.06e-3 ✓ sig.
Iron deficiency anemia Iron-refractory iron deficiency anemia 0.083 1 1.30e-3 2.06e-3 ✓ sig.
Iron metabolism disorder TFRC-related combined immunodeficiency 0.043 1 1.43e-3 2.22e-3 ✓ sig.
Iron metabolism disorder lessel-kreienkamp syndrome 0.043 1 1.43e-3 2.22e-3 ✓ sig.
IRIDA syndrome Iron metabolism disorder 0.043 1 1.43e-3 2.22e-3 ✓ sig.
Iron metabolism disorder Iron-refractory iron deficiency anemia 0.042 1 2.86e-3 3.81e-3 ✓ sig.