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 90

13 diseases · 26 shared-gene connections
13 Diseases
34 Unique genes
0.281 Avg. similarity score
Leukocyte disorders Most-connected disease (7 links)
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Disease Searched: Leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome 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 ⇵
Leukocyte disorders 7 7 3
Dysplasminogenemia 6 6 1
Hypoplasminogenemia 6 6 1
Plasminogen deficiency 6 6 1
Plasminogen deficiency, type i 6 6 1
Laryngeal disease 5 5 6
Conjunctivitis 4 4 2
Autoimmune lymphoproliferative immune disorder 3 3 1
Splenic disease 3 3 9
Splenomegaly 2 2 21
Thyroid gland mucosa-associated lymphoid tissue lymphoma 2 2 2
Leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome 1 1 1
Palmoplantar keratoderma, punctate type 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
PLG 8 / 13 Conjunctivitis, Dysplasminogenemia, Hypoplasminogenemia, Laryngeal disease and 4 more
FAS 5 / 13 Autoimmune lymphoproliferative immune disorder, Leukocyte disorders, Splenic disease, Splenomegaly and 1 more
AHR 2 / 13 Splenic disease, Splenomegaly
APC 2 / 13 Splenic disease, Splenomegaly
CCDC91 2 / 13 Laryngeal disease, Palmoplantar keratoderma, punctate type
CYP1A2 2 / 13 Splenic disease, Splenomegaly
EIF2AK1 2 / 13 Leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome, Splenomegaly
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
FAS, JAK2, APC, BDKRB1, FLT3, KRAS, MECOM, NFE2L2, NOTCH1, NRAS, STAT5B, XIAP
 KEGG 12 / 533 8.0× 1.16e-8 8.43e-7 ✓ sig.
FLT3 Signaling
FLT3, KRAS, NRAS
 Reactome 3 / 7 151× 7.20e-7 3.14e-5 ✓ sig.
Chemical carcinogenesis - receptor activation
JAK2, AHR, CYP1A2, KRAS, NRAS, STAT5B, XIAP
 KEGG 7 / 215 11.5× 1.91e-6 7.26e-5 ✓ sig.
Signaling by SCF-KIT
JAK2, KRAS, NRAS, STAT5B
 Reactome 4 / 37 38.2× 3.31e-6 1.16e-4 ✓ sig.
Alzheimer disease
FAS, APC, APOE, APP, KRAS, MAPT, NRAS, PSEN1
 KEGG 8 / 388 7.3× 9.59e-6 2.81e-4 ✓ sig.
RAS GTPase cycle mutants
KRAS, NRAS
 Reactome 2 / 3 235× 2.33e-5 5.91e-4 ✓ sig.
Acute myeloid leukemia
FLT3, KRAS, NRAS, STAT5B
 KEGG 4 / 68 20.8× 3.84e-5 8.85e-4 ✓ sig.
Prolactin signaling pathway
JAK2, KRAS, NRAS, STAT5B
 KEGG 4 / 71 19.9× 4.55e-5 1.01e-3 ✓ sig.
Chronic myeloid leukemia
KRAS, MECOM, NRAS, STAT5B
 KEGG 4 / 77 18.3× 6.26e-5 1.31e-3 ✓ sig.
Downstream signal transduction
KRAS, NRAS, STAT5B
 Reactome 3 / 29 36.5× 7.20e-5 1.46e-3 ✓ sig.
Activation of RAS in B cells
KRAS, NRAS
 Reactome 2 / 5 141× 7.74e-5 1.55e-3 ✓ sig.
Hepatitis C
FAS, EIF2AK1, KRAS, NRAS, OCLN
 KEGG 5 / 159 11.1× 7.79e-5 1.56e-3 ✓ sig.
Hepatitis B
FAS, JAK2, KRAS, NRAS, STAT5B
 KEGG 5 / 163 10.8× 8.76e-5 1.71e-3 ✓ sig.
RAF activation
JAK2, KRAS, NRAS
 Reactome 3 / 32 33.1× 9.72e-5 1.85e-3 ✓ sig.
Estrogen-stimulated signaling through PRKCZ
KRAS, NRAS
 Reactome 2 / 6 118× 1.16e-4 2.13e-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 ⇵
positive regulation of nitric oxide biosynthetic process
ITGB2, JAK2, APOE, APP, HBB
 GO:0045429 5 / 42 65.4× 1.19e-8 2.05e-6 ✓ sig.
positive regulation of amyloid fibril formation
APOE, APP, PSEN1
 GO:1905908 3 / 5 330× 5.49e-8 7.67e-6 ✓ sig.
microglial cell activation
ITGB2, JAK2, APP, MAPT
 GO:0001774 4 / 28 78.5× 1.81e-7 2.08e-5 ✓ sig.
astrocyte activation
APP, MAPT, PSEN1
 GO:0048143 3 / 17 97.0× 3.68e-6 2.47e-4 ✓ sig.
apoptotic process
FAS, ITGB2, JAK2, AHR, APP, MECOM, NOTCH1, PSEN1, XIAP
 GO:0006915 9 / 747 6.6× 5.30e-6 3.31e-4 ✓ sig.
positive regulation of superoxide anion generation
ITGB2, APP, MAPT
 GO:0032930 3 / 20 82.4× 6.14e-6 3.73e-4 ✓ sig.
regulation of amyloid-beta clearance
APOE, APP
 GO:1900221 2 / 3 366× 9.63e-6 5.28e-4 ✓ sig.
regulation of amyloid fibril formation
APOE, APP
 GO:1905906 2 / 3 366× 9.63e-6 5.28e-4 ✓ sig.
negative regulation of programmed cell death
MECOM, NOTCH1, PEPD
 GO:0043069 3 / 26 63.4× 1.39e-5 7.03e-4 ✓ sig.
astrocyte activation involved in immune response
APP, PSEN1
 GO:0002265 2 / 4 275× 1.92e-5 8.98e-4 ✓ sig.
positive regulation of cell activation
JAK2, APP
 GO:0050867 2 / 4 275× 1.92e-5 8.98e-4 ✓ sig.
positive regulation of apoptotic process
FAS, JAK2, APC, APP, NOTCH1, PSEN1
 GO:0043065 6 / 326 10.1× 2.40e-5 1.06e-3 ✓ sig.
regulation of innate immune response
APOE, NFE2L2, XIAP
 GO:0045088 3 / 32 51.5× 2.63e-5 1.13e-3 ✓ sig.
negative regulation of gene expression
APOE, APP, MAPT, NOTCH1, OCLN, PSEN1
 GO:0010629 6 / 339 9.7× 2.99e-5 1.25e-3 ✓ sig.
negative regulation of cardiac muscle cell apoptotic process
JAK2, NFE2L2, NOTCH1
 GO:0010667 3 / 35 47.1× 3.46e-5 1.40e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Splenic disease Splenomegaly 0.154 4 2.54e-10 2.30e-9 ✓ sig.
Leukocyte disorders Splenic disease 0.182 2 9.00e-7 5.50e-6 ✓ sig.
Dysplasminogenemia Hypoplasminogenemia 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Dysplasminogenemia Plasminogen deficiency, type i 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Dysplasminogenemia Plasminogen deficiency 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Plasminogen deficiency Plasminogen deficiency, type i 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Hypoplasminogenemia Plasminogen deficiency, type i 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Hypoplasminogenemia Plasminogen deficiency 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Conjunctivitis Hypoplasminogenemia 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Conjunctivitis Dysplasminogenemia 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Conjunctivitis Plasminogen deficiency, type i 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Conjunctivitis Plasminogen deficiency 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Autoimmune lymphoproliferative immune disorder Thyroid gland mucosa-associated lymphoid tissue lymphoma 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Leukocyte disorders Plasminogen deficiency 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Leukocyte disorders Plasminogen deficiency, type i 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Hypoplasminogenemia Leukocyte disorders 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Dysplasminogenemia Leukocyte disorders 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Autoimmune lymphoproliferative immune disorder Leukocyte disorders 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Leukocyte disorders Thyroid gland mucosa-associated lymphoid tissue lymphoma 0.200 1 3.87e-4 7.33e-4 ✓ sig.
Laryngeal disease Plasminogen deficiency 0.143 1 3.87e-4 7.33e-4 ✓ sig.
Laryngeal disease Plasminogen deficiency, type i 0.143 1 3.87e-4 7.33e-4 ✓ sig.
Dysplasminogenemia Laryngeal disease 0.143 1 3.87e-4 7.33e-4 ✓ sig.
Hypoplasminogenemia Laryngeal disease 0.143 1 3.87e-4 7.33e-4 ✓ sig.
Laryngeal disease Palmoplantar keratoderma, punctate type 0.143 1 3.87e-4 7.33e-4 ✓ sig.
Autoimmune lymphoproliferative immune disorder Splenic disease 0.100 1 5.81e-4 1.00e-3 ✓ sig.
Leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome Splenomegaly 0.048 1 1.29e-3 1.89e-3 ✓ sig.