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 105

11 diseases · 16 shared-gene connections
11 Diseases
137 Unique genes
0.141 Avg. similarity score
Hereditary hemolytic anemia Most-connected disease (6 links)
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Disease Searched: inherited glutathione synthetase deficiency 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 ⇵
Hereditary hemolytic anemia 6 6 11
Bisphosphoglycerate mutase deficiency 4 4 1
Erythrocytosis 4 4 13
Hemolytic anemia 4 4 55
Polycythemia 4 4 19
Secondary polycythemia 4 4 8
Anemia 2 2 84
Charcot-Marie-Tooth disease type 4B2 1 1 1
Cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome 1 1 1
Coronary vessel anomalies 1 1 1
inherited glutathione synthetase deficiency 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
HBB 6 / 11 Anemia, Erythrocytosis, Hemolytic anemia, Hereditary hemolytic anemia and 2 more
BPGM 5 / 11 Bisphosphoglycerate mutase deficiency, Erythrocytosis, Hemolytic anemia, Hereditary hemolytic anemia and 1 more
EPO 5 / 11 Anemia, Erythrocytosis, Hemolytic anemia, Polycythemia and 1 more
HBA1 4 / 11 Anemia, Erythrocytosis, Polycythemia, Secondary polycythemia
HK1 4 / 11 Anemia, Hemolytic anemia, Hereditary hemolytic anemia, Polycythemia
EGLN1 3 / 11 Erythrocytosis, Polycythemia, Secondary polycythemia
EPAS1 3 / 11 Erythrocytosis, Polycythemia, Secondary polycythemia
EPOR 3 / 11 Anemia, Erythrocytosis, Polycythemia
GCLC 3 / 11 Coronary vessel anomalies, Hemolytic anemia, Hereditary hemolytic anemia
HBA2 3 / 11 Anemia, Erythrocytosis, Secondary polycythemia
JAK2 3 / 11 Anemia, Erythrocytosis, Polycythemia
VHL 3 / 11 Erythrocytosis, Polycythemia, Secondary polycythemia
ABO 2 / 11 Anemia, Hemolytic anemia
ACE 2 / 11 Anemia, Polycythemia
ANK1 2 / 11 Anemia, Hemolytic anemia
FAM234A 2 / 11 Anemia, Hereditary hemolytic anemia
G6PD 2 / 11 Anemia, Hemolytic anemia
GATA1 2 / 11 Anemia, Hemolytic anemia
GH1 2 / 11 Anemia, Polycythemia
GPI 2 / 11 Hemolytic anemia, Hereditary hemolytic anemia
GPX1 2 / 11 Anemia, Hereditary hemolytic anemia
GSR 2 / 11 Anemia, Hemolytic anemia
GSS 2 / 11 Hereditary hemolytic anemia, inherited glutathione synthetase deficiency
H2BC4 2 / 11 Anemia, Polycythemia
HFE 2 / 11 Anemia, Polycythemia
HP 2 / 11 Anemia, Hemolytic anemia
IFNA2 2 / 11 Anemia, Hemolytic anemia
INSL6 2 / 11 Erythrocytosis, Polycythemia
ITPA 2 / 11 Anemia, Hemolytic anemia
LUC7L 2 / 11 Anemia, Hereditary hemolytic anemia
PRKCE 2 / 11 Anemia, Polycythemia
SBF2 2 / 11 Charcot-Marie-Tooth disease type 4B2, Hemolytic anemia
SHH 2 / 11 Anemia, Hemolytic anemia
SLC30A10 2 / 11 Cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome, Polycythemia
SPTA1 2 / 11 Anemia, Hemolytic anemia
SPTB 2 / 11 Anemia, Hemolytic anemia
TMPRSS6 2 / 11 Anemia, Polycythemia
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
ATG5, ATG7, SLC11A2, SLC40A1, TF, GCLC, HMOX1, GSS
 KEGG 8 / 42 16.7× 1.99e-8 1.68e-6 ✓ sig.
Erythrocytes take up oxygen and release carbon dioxide
HBA1, HBA2, HBB, RHAG, SLC4A1
 Reactome 5 / 9 48.7× 2.18e-8 1.83e-6 ✓ sig.
Scavenging of heme from plasma
APOL1, HBA1, HBA2, HBB, HP
 Reactome 5 / 13 33.7× 2.15e-7 1.36e-5 ✓ sig.
Erythrocytes take up carbon dioxide and release oxygen
HBA1, HBA2, HBB, RHAG, SLC4A1
 Reactome 5 / 13 33.7× 2.15e-7 1.36e-5 ✓ sig.
Glycolysis
HK1, GPI, PGK1, PKLR, TPI1, BPGM
 Reactome 6 / 28 18.8× 6.05e-7 3.35e-5 ✓ sig.
Pathways in cancer
AGT, CDK6, EPO, EPOR, IFNA2, IGF2, IL2, IL3, ITGA3, JAK2, KRAS, NRAS
 KEGG 19 / 533 3.1× 9.58e-6 3.42e-4 ✓ sig.
Iron uptake and transport
SLC11A2, SLC40A1, SLC46A1, TF, HMOX1
 Reactome 5 / 28 15.7× 1.43e-5 4.76e-4 ✓ sig.
PI3K-Akt signaling pathway
CDK6, CSF3, EPO, EPOR, GH1, IFNA2, IGF2, IL2, IL3, ITGA3, JAK2, KRAS
 KEGG 15 / 361 3.6× 1.53e-5 5.05e-4 ✓ sig.
Hematopoietic cell lineage
CSF2, CSF3, EPO, EPOR, IL3, ITGA3, TNF, CD59
 KEGG 8 / 100 7.0× 1.80e-5 5.76e-4 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
AGT, JAK2, KRAS, NRAS, PRKCE, TNF, COL4A1, PRKCZ
 KEGG 8 / 101 6.9× 1.94e-5 6.14e-4 ✓ sig.
JAK-STAT signaling pathway
CSF2, CSF3, EPO, EPOR, GH1, IFNA2, IL2, IL3, JAK2, PRL
 KEGG 10 / 168 5.2× 2.18e-5 6.79e-4 ✓ sig.
Estrogen-stimulated signaling through PRKCZ
KRAS, NRAS, PRKCZ
 Reactome 3 / 6 43.8× 2.83e-5 8.40e-4 ✓ sig.
HIF-1 signaling pathway
EPO, HK1, TF, HMOX1, PGK1, EGLN1, EPAS1, VHL
 KEGG 8 / 110 6.4× 3.60e-5 1.02e-3 ✓ sig.
African trypanosomiasis
APOL1, HBA1, HBA2, HBB, TNF
 KEGG 5 / 37 11.8× 5.84e-5 1.51e-3 ✓ sig.
Mineral absorption
ATP7A, SLC11A2, SLC40A1, SLC46A1, TF, HMOX1
 KEGG 6 / 61 8.6× 6.55e-5 1.66e-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 ⇵
multicellular organismal-level iron ion homeostasis
HAMP, HFE, SLC11A2, SLC40A1, SOD2, TF, TMPRSS6, EIF2AK1, HMOX1, RHAG, EPAS1
 GO:0060586 11 / 28 53.6× 4.22e-17 4.22e-14 ✓ sig.
erythrocyte development
GATA1, HBA1, HBA2, HBB, SLC11A2, RHAG, SLC4A1, BPGM, SH2B3
 GO:0048821 9 / 32 38.4× 1.14e-12 5.23e-10 ✓ sig.
intracellular iron ion homeostasis
HAMP, HFE, SLC11A2, SLC40A1, SLC46A1, TF, TMPRSS6, HMOX1, EGLN1
 GO:0006879 9 / 71 17.3× 2.38e-9 4.84e-7 ✓ sig.
response to hydrogen peroxide
GPX1, HBA1, HBA2, HBB, HP, SOD2, HMOX1
 GO:0042542 7 / 39 24.5× 1.23e-8 2.05e-6 ✓ sig.
cell surface receptor signaling pathway via STAT
CSF2, EPO, GH1, IFNA2, IL2, IL3
 GO:0097696 6 / 28 29.2× 4.59e-8 6.34e-6 ✓ sig.
response to nutrient levels
ATG7, GH1, PRL, PTH, SOD2, TNF, ABCG5, ABCG8
 GO:0031667 8 / 79 13.8× 1.14e-7 1.38e-5 ✓ sig.
response to xenobiotic stimulus
ATG5, GPX1, ITGA3, MTHFR, PTH, REN, SOD2, TNF, UMOD, GCLC, ABCG5, ABCG8
 GO:0009410 12 / 248 6.6× 2.94e-7 3.08e-5 ✓ sig.
response to cadmium ion
PTH, SOD2, GCLC, GPI, GSS
 GO:0046686 5 / 21 32.5× 3.64e-7 3.68e-5 ✓ sig.
iron ion export across plasma membrane
HAMP, SLC40A1, TF
 GO:1903988 3 / 3 136× 3.86e-7 3.85e-5 ✓ sig.
glycolytic process
HK1, GPI, PGK1, PKLR, TPI1, BPGM
 GO:0006096 6 / 49 16.7× 1.50e-6 1.19e-4 ✓ sig.
response to isolation stress
KRAS, SOD2, TNF
 GO:0035900 3 / 4 102× 1.53e-6 1.21e-4 ✓ sig.
carbon dioxide transport
HBA1, HBA2, HBB, RHAG
 GO:0015670 4 / 13 42.0× 1.88e-6 1.42e-4 ✓ sig.
iron ion transport
HFE, SLC11A2, SLC25A37, SLC40A1, TF
 GO:0006826 5 / 31 22.0× 2.87e-6 1.98e-4 ✓ sig.
maintenance of blood vessel diameter homeostasis by renin-angiotensin
ACE, AGT, REN
 GO:0002034 3 / 5 81.8× 3.81e-6 2.49e-4 ✓ sig.
nitric oxide transport
HBA1, HBA2, HBB
 GO:0030185 3 / 5 81.8× 3.81e-6 2.49e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Erythrocytosis Secondary polycythemia 0.571 8 1.65e-26 4.41e-25 ✓ sig.
Erythrocytosis Polycythemia 0.375 9 4.93e-25 1.20e-23 ✓ sig.
Anemia Polycythemia 0.130 12 1.50e-23 3.36e-22 ✓ sig.
Anemia Hemolytic anemia 0.111 14 2.42e-20 4.67e-19 ✓ sig.
Polycythemia Secondary polycythemia 0.273 6 4.10e-17 6.74e-16 ✓ sig.
Hemolytic anemia Hereditary hemolytic anemia 0.081 5 2.19e-10 2.12e-9 ✓ sig.
Hereditary hemolytic anemia Secondary polycythemia 0.111 2 1.30e-5 6.32e-5 ✓ sig.
Erythrocytosis Hereditary hemolytic anemia 0.087 2 3.60e-5 1.66e-4 ✓ sig.
Bisphosphoglycerate mutase deficiency Secondary polycythemia 0.111 1 5.20e-4 1.06e-3 ✓ sig.
Bisphosphoglycerate mutase deficiency Hereditary hemolytic anemia 0.083 1 7.14e-4 1.34e-3 ✓ sig.
Coronary vessel anomalies Hereditary hemolytic anemia 0.083 1 7.14e-4 1.34e-3 ✓ sig.
Hereditary hemolytic anemia inherited glutathione synthetase deficiency 0.083 1 7.14e-4 1.34e-3 ✓ sig.
Bisphosphoglycerate mutase deficiency Erythrocytosis 0.071 1 8.44e-4 1.50e-3 ✓ sig.
Cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome Polycythemia 0.050 1 1.23e-3 1.99e-3 ✓ sig.
Bisphosphoglycerate mutase deficiency Hemolytic anemia 0.018 1 3.57e-3 4.59e-3 ✓ sig.
Charcot-Marie-Tooth disease type 4B2 Hemolytic anemia 0.018 1 3.57e-3 4.59e-3 ✓ sig.