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 24

20 diseases · 60 shared-gene connections
20 Diseases
140 Unique genes
0.341 Avg. similarity score
Hemoglobin m disease Most-connected disease (12 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 ⇵
Hemoglobin m disease 12 12 3
erythrocytosis, familial, 7 10 10 2
methemoglobinemia, alpha type 10 10 2
Thalassemia 8 8 5
Unstable hemoglobin disease 8 8 3
Alpha thalassemia 7 7 3
Hemoglobin barts fetalis syndrome 7 7 3
Hemoglobin h disease 7 7 3
Methemoglobinemia 7 7 6
Polycythemia vera 6 6 9
Secondary polycythemia 6 6 8
Erythrocytosis 5 5 13
HBA1-related alpha thalassemia spectrum 5 5 1
HBA2-related alpha thalassemia spectrum 5 5 1
Polycythemia 5 5 19
Chloracne 4 4 33
Hematologic disease 3 3 18
Anemia 2 2 84
Bisphosphoglycerate mutase deficiency 2 2 1
methemoglobinemia type 4 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
HBA1 16 / 20 Alpha thalassemia, Anemia, Chloracne, Erythrocytosis and 12 more
HBA2 14 / 20 Alpha thalassemia, Anemia, Chloracne, Erythrocytosis and 10 more
HBB 10 / 20 Anemia, Chloracne, Erythrocytosis, Hemoglobin m disease and 6 more
JAK2 5 / 20 Anemia, Erythrocytosis, Hematologic disease, Polycythemia and 1 more
EPO 4 / 20 Anemia, Erythrocytosis, Polycythemia, Secondary polycythemia
H2BC4 4 / 20 Anemia, Hematologic disease, Polycythemia, Polycythemia vera
ATRX 3 / 20 Alpha thalassemia, Hemoglobin barts fetalis syndrome, Hemoglobin h disease
BPGM 3 / 20 Bisphosphoglycerate mutase deficiency, Erythrocytosis, Secondary polycythemia
EGLN1 3 / 20 Erythrocytosis, Polycythemia, Secondary polycythemia
EPAS1 3 / 20 Erythrocytosis, Polycythemia, Secondary polycythemia
EPOR 3 / 20 Anemia, Erythrocytosis, Polycythemia
H1-2 3 / 20 Anemia, Hematologic disease, Polycythemia vera
HFE 3 / 20 Anemia, Hematologic disease, Polycythemia
VHL 3 / 20 Erythrocytosis, Polycythemia, Secondary polycythemia
ACE 2 / 20 Anemia, Polycythemia
CDK6 2 / 20 Anemia, Chloracne
CYB5A 2 / 20 Methemoglobinemia, methemoglobinemia type 4
GH1 2 / 20 Anemia, Polycythemia
GSTM1 2 / 20 Chloracne, Thalassemia
HBD 2 / 20 Chloracne, Thalassemia
HBS1L 2 / 20 Anemia, Hematologic disease
HK1 2 / 20 Anemia, Polycythemia
HOXD13 2 / 20 Anemia, Hematologic disease
IFNA2 2 / 20 Anemia, Polycythemia vera
INSL6 2 / 20 Erythrocytosis, Polycythemia
MTHFR 2 / 20 Anemia, Hematologic disease
NUP98 2 / 20 Anemia, Hematologic disease
PRKCE 2 / 20 Anemia, Polycythemia
TMPRSS6 2 / 20 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 ⇵
Pathways in cancer
AGT, CDK6, EPO, EPOR, IFNA2, IGF2, IL2, IL3, ITGA3, JAK2, KRAS, NRAS
 KEGG 26 / 533 4.2× 4.23e-10 5.24e-8 ✓ sig.
Scavenging of heme from plasma
HBA1, HBA2, APOL1, HBB, HP
 Reactome 5 / 13 33.0× 2.39e-7 1.40e-5 ✓ sig.
JAK-STAT signaling pathway
CSF2, CSF3, EPO, EPOR, GH1, IFNA2, IL2, IL3, JAK2, PRL, EGFR, OSM
 KEGG 12 / 168 6.1× 5.87e-7 3.07e-5 ✓ sig.
PI3K-Akt signaling pathway
CDK6, CSF3, EPO, EPOR, GH1, IFNA2, IGF2, IL2, IL3, ITGA3, JAK2, KRAS
 KEGG 17 / 361 4.0× 9.83e-7 4.80e-5 ✓ sig.
Erythrocytes take up oxygen and release carbon dioxide
HBA1, HBA2, HBB, SLC4A1
 Reactome 4 / 9 38.1× 2.13e-6 9.27e-5 ✓ sig.
African trypanosomiasis
HBA1, HBA2, APOL1, HBB, TNF, FAS
 KEGG 6 / 37 13.9× 3.89e-6 1.55e-4 ✓ sig.
Hepatocellular carcinoma
CDK6, IGF2, KRAS, NRAS, TCF7L2, EGFR, GADD45A, GSTM1, GSTM3, SMARCB1, GSTP1
 KEGG 11 / 170 5.6× 4.63e-6 1.79e-4 ✓ sig.
Cytokine-cytokine receptor interaction
CSF2, CSF3, EPO, EPOR, GH1, IFNA2, IL2, IL3, PRL, TNF, TNFRSF10A, CX3CR1
 KEGG 14 / 298 4.0× 9.72e-6 3.28e-4 ✓ sig.
Erythrocytes take up carbon dioxide and release oxygen
HBA1, HBA2, HBB, SLC4A1
 Reactome 4 / 13 26.4× 1.17e-5 3.81e-4 ✓ sig.
RAF/MAP kinase cascade
CSF2, IL2, IL3, JAK2, KRAS, NRAS, SPTA1, SPTB, EGFR
 Reactome 9 / 124 6.2× 1.40e-5 4.44e-4 ✓ sig.
Factors involved in megakaryocyte development and platelet production
GATA1, GATA2, HBB, IFNA2, JAK2, HBD, HBG1, SH2B3
 Reactome 8 / 99 6.9× 1.96e-5 5.88e-4 ✓ sig.
Malaria
HBA1, HBA2, CSF3, HBB, TNF, ITGB2
 KEGG 6 / 50 10.3× 2.35e-5 6.81e-4 ✓ sig.
Platinum drug resistance
ATP7A, ERCC1, CYCS, GSTM1, GSTM3, FAS, GSTP1
 KEGG 7 / 75 8.0× 2.58e-5 7.34e-4 ✓ sig.
Apoptosis
IL3, KRAS, NRAS, PARP1, TNF, TNFRSF10A, CYCS, GADD45A, FAS
 KEGG 9 / 137 5.6× 3.11e-5 8.61e-4 ✓ sig.
HIF-1 signaling pathway
EPO, HK1, TF, EGLN1, EPAS1, VHL, CDKN1B, EGFR
 KEGG 8 / 110 6.2× 4.21e-5 1.11e-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 ⇵
erythrocyte development
HBA1, HBA2, GATA1, HBB, SLC11A2, BPGM, HBD, HBG1, SH2B3, SLC4A1
 GO:0048821 10 / 32 41.7× 2.25e-14 1.38e-11 ✓ sig.
multicellular organismal-level iron ion homeostasis
HAMP, HFE, SLC11A2, SLC40A1, SOD2, TF, TMPRSS6, EPAS1
 GO:0060586 8 / 28 38.1× 2.22e-11 7.47e-9 ✓ sig.
oxygen transport
HBA1, HBA2, HBB, BPGM, HBD, HBG1
 GO:0015671 6 / 17 47.1× 1.84e-9 3.83e-7 ✓ sig.
response to nutrient levels
ATG7, GH1, PRL, PTH, SOD2, TNF, ALAD, GSTP1, DNMT3A
 GO:0031667 9 / 79 15.2× 7.57e-9 1.34e-6 ✓ sig.
carbon dioxide transport
HBA1, HBA2, HBB, HBD, HBG1
 GO:0015670 5 / 13 51.3× 2.69e-8 4.02e-6 ✓ sig.
cell surface receptor signaling pathway via STAT
CSF2, EPO, GH1, IFNA2, IL2, IL3
 GO:0097696 6 / 28 28.6× 5.22e-8 7.03e-6 ✓ sig.
intracellular iron ion homeostasis
HAMP, HFE, SLC11A2, SLC40A1, SLC46A1, TF, TMPRSS6, EGLN1
 GO:0006879 8 / 71 15.0× 5.80e-8 7.68e-6 ✓ sig.
glutathione metabolic process
G6PD, GPX1, GSR, SOD2, GSTM1, GSTM3, GSTP1
 GO:0006749 7 / 49 19.1× 7.53e-8 9.49e-6 ✓ sig.
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
AGT, CSF3, GH1, GPX1, IGF2, JAK2, TCF7L2, TNF, CD28, CX3CR1, EGFR, OSM
 GO:0051897 12 / 217 7.4× 8.77e-8 1.08e-5 ✓ sig.
iron ion export across plasma membrane
HAMP, SLC40A1, TF
 GO:1903988 3 / 3 133× 4.12e-7 3.97e-5 ✓ sig.
response to hydrogen peroxide
HBA1, HBA2, GPX1, HBB, HP, SOD2
 GO:0042542 6 / 39 20.5× 4.23e-7 4.05e-5 ✓ sig.
cellular oxidant detoxification
HBA1, HBA2, GPX1, GSR, HBB, HP, GSTP1
 GO:0098869 7 / 66 14.2× 6.14e-7 5.56e-5 ✓ sig.
embryonic placenta development
CSF2, GATA2, IGF2, EPAS1, EGFR
 GO:0001892 5 / 26 25.7× 1.27e-6 1.01e-4 ✓ sig.
response to isolation stress
KRAS, SOD2, TNF
 GO:0035900 3 / 4 100× 1.64e-6 1.23e-4 ✓ sig.
response to ethanol
CSF3, G6PD, IL2, PTH, TNF, ALAD, GSTP1, DNMT3A
 GO:0045471 8 / 110 9.7× 1.75e-6 1.29e-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 4.66e-25 ✓ sig.
Erythrocytosis Polycythemia 0.375 9 4.93e-25 1.27e-23 ✓ sig.
Anemia Polycythemia 0.130 12 1.50e-23 3.56e-22 ✓ sig.
Polycythemia Secondary polycythemia 0.273 6 4.10e-17 7.12e-16 ✓ sig.
Anemia Hematologic disease 0.084 8 2.33e-14 3.36e-13 ✓ sig.
Chloracne Thalassemia 0.147 5 3.29e-14 4.68e-13 ✓ sig.
Hemoglobin barts fetalis syndrome Hemoglobin h disease 0.750 3 1.64e-12 2.04e-11 ✓ sig.
Hemoglobin m disease Unstable hemoglobin disease 0.750 3 1.64e-12 2.04e-11 ✓ sig.
Alpha thalassemia Hemoglobin h disease 0.750 3 1.64e-12 2.04e-11 ✓ sig.
Alpha thalassemia Hemoglobin barts fetalis syndrome 0.750 3 1.64e-12 2.04e-11 ✓ sig.
Hemoglobin m disease Thalassemia 0.500 3 1.64e-11 1.88e-10 ✓ sig.
Thalassemia Unstable hemoglobin disease 0.500 3 1.64e-11 1.88e-10 ✓ sig.
Hemoglobin m disease Methemoglobinemia 0.429 3 3.29e-11 3.62e-10 ✓ sig.
Methemoglobinemia Unstable hemoglobin disease 0.429 3 3.29e-11 3.62e-10 ✓ sig.
Secondary polycythemia Unstable hemoglobin disease 0.333 3 9.21e-11 9.69e-10 ✓ sig.
Hemoglobin m disease Secondary polycythemia 0.333 3 9.21e-11 9.69e-10 ✓ sig.
Polycythemia Polycythemia vera 0.160 4 2.08e-10 2.13e-9 ✓ sig.
Methemoglobinemia Thalassemia 0.333 3 3.29e-10 3.31e-9 ✓ sig.
Erythrocytosis Hemoglobin m disease 0.214 3 4.70e-10 4.65e-9 ✓ sig.
Secondary polycythemia Thalassemia 0.273 3 9.20e-10 8.83e-9 ✓ sig.
erythrocytosis, familial, 7 methemoglobinemia, alpha type 0.667 2 8.44e-9 7.20e-8 ✓ sig.
Chloracne Unstable hemoglobin disease 0.088 3 8.97e-9 7.62e-8 ✓ sig.
Chloracne Hemoglobin m disease 0.088 3 8.97e-9 7.62e-8 ✓ sig.
methemoglobinemia, alpha type Unstable hemoglobin disease 0.500 2 2.53e-8 2.03e-7 ✓ sig.
Hemoglobin m disease methemoglobinemia, alpha type 0.500 2 2.53e-8 2.03e-7 ✓ sig.
Hemoglobin h disease methemoglobinemia, alpha type 0.500 2 2.53e-8 2.03e-7 ✓ sig.
Hemoglobin barts fetalis syndrome methemoglobinemia, alpha type 0.500 2 2.53e-8 2.03e-7 ✓ sig.
erythrocytosis, familial, 7 Unstable hemoglobin disease 0.500 2 2.53e-8 2.03e-7 ✓ sig.
Alpha thalassemia methemoglobinemia, alpha type 0.500 2 2.53e-8 2.03e-7 ✓ sig.
Alpha thalassemia erythrocytosis, familial, 7 0.500 2 2.53e-8 2.03e-7 ✓ sig.
erythrocytosis, familial, 7 Hemoglobin barts fetalis syndrome 0.500 2 2.53e-8 2.03e-7 ✓ sig.
erythrocytosis, familial, 7 Hemoglobin h disease 0.500 2 2.53e-8 2.03e-7 ✓ sig.
erythrocytosis, familial, 7 Hemoglobin m disease 0.500 2 2.53e-8 2.03e-7 ✓ sig.
Erythrocytosis Polycythemia vera 0.150 3 3.94e-8 3.12e-7 ✓ sig.
Hemoglobin barts fetalis syndrome Hemoglobin m disease 0.400 2 7.59e-8 5.72e-7 ✓ sig.
Alpha thalassemia Hemoglobin m disease 0.400 2 7.59e-8 5.72e-7 ✓ sig.
Hemoglobin h disease Hemoglobin m disease 0.400 2 7.59e-8 5.72e-7 ✓ sig.
erythrocytosis, familial, 7 Thalassemia 0.333 2 8.44e-8 6.27e-7 ✓ sig.
methemoglobinemia, alpha type Thalassemia 0.333 2 8.44e-8 6.27e-7 ✓ sig.
Hematologic disease Polycythemia vera 0.120 3 1.12e-7 8.25e-7 ✓ sig.
erythrocytosis, familial, 7 Methemoglobinemia 0.286 2 1.27e-7 9.20e-7 ✓ sig.
Methemoglobinemia methemoglobinemia, alpha type 0.286 2 1.27e-7 9.20e-7 ✓ sig.
Chloracne Methemoglobinemia 0.081 3 1.79e-7 1.26e-6 ✓ sig.
Hemoglobin m disease Polycythemia vera 0.182 2 9.11e-7 5.67e-6 ✓ sig.
Polycythemia vera Unstable hemoglobin disease 0.182 2 9.11e-7 5.67e-6 ✓ sig.
Hematologic disease Polycythemia 0.086 3 1.28e-6 7.82e-6 ✓ sig.
Polycythemia vera Thalassemia 0.154 2 3.03e-6 1.72e-5 ✓ sig.
erythrocytosis, familial, 7 HBA1-related alpha thalassemia spectrum 0.333 1 1.30e-4 3.90e-4 ✓ sig.
HBA1-related alpha thalassemia spectrum methemoglobinemia, alpha type 0.333 1 1.30e-4 3.90e-4 ✓ sig.
erythrocytosis, familial, 7 HBA2-related alpha thalassemia spectrum 0.333 1 1.30e-4 3.90e-4 ✓ sig.
HBA2-related alpha thalassemia spectrum methemoglobinemia, alpha type 0.333 1 1.30e-4 3.90e-4 ✓ sig.
HBA2-related alpha thalassemia spectrum Hemoglobin h disease 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Alpha thalassemia HBA2-related alpha thalassemia spectrum 0.250 1 1.95e-4 5.28e-4 ✓ sig.
HBA1-related alpha thalassemia spectrum Hemoglobin h disease 0.250 1 1.95e-4 5.28e-4 ✓ sig.
HBA1-related alpha thalassemia spectrum Hemoglobin barts fetalis syndrome 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Alpha thalassemia HBA1-related alpha thalassemia spectrum 0.250 1 1.95e-4 5.28e-4 ✓ sig.
HBA2-related alpha thalassemia spectrum Hemoglobin barts fetalis syndrome 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Methemoglobinemia methemoglobinemia type 4 0.143 1 3.90e-4 8.52e-4 ✓ sig.
Bisphosphoglycerate mutase deficiency Secondary polycythemia 0.111 1 5.20e-4 1.04e-3 ✓ sig.
Bisphosphoglycerate mutase deficiency Erythrocytosis 0.071 1 8.44e-4 1.48e-3 ✓ sig.