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 176

9 diseases · 20 shared-gene connections
9 Diseases
12 Unique genes
0.283 Avg. similarity score
Combined cellular and humoral immune defects with granulomas Most-connected disease (6 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 ⇵
Combined cellular and humoral immune defects with granulomas 6 6 2
Combined immunodeficiency with granulomatosis 6 6 3
Combined immunodeficiency with skin granulomas 6 6 2
Omenn syndrome 6 6 10
Salla disease 5 5 2
recombinase activating gene 2 deficiency 5 5 1
recombinase activating gene 1 deficiency 4 4 1
free sialic acid storage disease 1 1 1
severe combined immunodeficiency due to DCLRE1C deficiency 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
RAG2 6 / 9 Combined cellular and humoral immune defects with granulomas, Combined immunodeficiency with granulomatosis, Combined immunodeficiency with skin granulomas, Omenn syndrome and 2 more
RAG1 5 / 9 Combined cellular and humoral immune defects with granulomas, Combined immunodeficiency with granulomatosis, Combined immunodeficiency with skin granulomas, Omenn syndrome and 1 more
DCLRE1C 2 / 9 Omenn syndrome, severe combined immunodeficiency due to DCLRE1C deficiency
SLC17A5 2 / 9 free sialic acid storage disease, Salla disease
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 ⇵
Primary immunodeficiency
RAG1, RAG2, ADA, DCLRE1C, IL2RG, IL7R
 KEGG 6 / 38 158× 6.04e-13 1.37e-10 ✓ sig.
Non-homologous end-joining
DCLRE1C, LIG4
 KEGG 2 / 13 154× 7.10e-5 1.70e-3 ✓ sig.
MAPK6/MAPK4 signaling
RAG1, RAG2, PSMB10
 Reactome 3 / 89 33.7× 8.25e-5 1.92e-3 ✓ sig.
FoxO signaling pathway
RAG1, RAG2, IL7R
 KEGG 3 / 133 22.6× 2.72e-4 4.96e-3 ✓ sig.
Interleukin-7 signaling
IL2RG, IL7R
 Reactome 2 / 33 60.7× 4.75e-4 7.66e-3 ✓ sig.
Defective SLC17A5 causes Salla disease (SD) and ISSD
SLC17A5
 Reactome 1 / 1 1,001× 9.99e-4 1.35e-2 ✓ sig.
Nonhomologous End-Joining (NHEJ)
DCLRE1C, LIG4
 Reactome 2 / 69 29.0× 2.07e-3 2.34e-2 ✓ sig.
UCH proteinases
INO80, PSMB10
 Reactome 2 / 97 20.6× 4.04e-3 3.80e-2 ✓ sig.
2-LTR circle formation
LIG4
 Reactome 1 / 7 143× 6.97e-3 5.45e-2
Interleukin-9 signaling
IL2RG
 Reactome 1 / 9 111× 8.96e-3 6.42e-2
Organic anion transporters
SLC17A5
 Reactome 1 / 10 100× 9.95e-3 6.82e-2
Interleukin-21 signaling
IL2RG
 Reactome 1 / 10 100× 9.95e-3 6.82e-2
JAK-STAT signaling pathway
IL2RG, IL7R
 KEGG 2 / 168 11.9× 1.17e-2 7.54e-2
Interleukin-2 signaling
IL2RG
 Reactome 1 / 12 83.4× 1.19e-2 7.61e-2
Purine salvage
ADA
 Reactome 1 / 13 77.0× 1.29e-2 7.95e-2

Enriched GO Terms (Biological Process, a second line of biological evidence)

GO term ⇵ GO ID ⇵ Overlap genes ⇵ Fold enrichment ⇵ P-value ⇵ FDR q-value ⇵
T cell differentiation in thymus
RAG1, RAG2, ADA, IL2RG, IL7R, LIG4
 GO:0033077 6 / 41 228× 6.96e-14 3.92e-11 ✓ sig.
V(D)J recombination
RAG1, RAG2, DCLRE1C, LIG4
 GO:0033151 4 / 11 566× 3.21e-11 1.03e-8 ✓ sig.
DNA recombination
RAG1, RAG2, INO80, DCLRE1C, LIG4
 GO:0006310 5 / 110 70.8× 4.94e-9 9.23e-7 ✓ sig.
T cell differentiation
RAG2, ADA, CHD7, IL7R
 GO:0030217 4 / 54 115× 3.03e-8 4.43e-6 ✓ sig.
positive regulation of T cell differentiation in thymus
ADA, IL2RG, IL7R
 GO:0033089 3 / 11 425× 3.33e-8 4.80e-6 ✓ sig.
B cell differentiation
RAG1, RAG2, DCLRE1C, IL2RG
 GO:0030183 4 / 80 77.9× 1.50e-7 1.71e-5 ✓ sig.
DN2 thymocyte differentiation
RAG2, LIG4
 GO:1904155 2 / 4 779× 2.27e-6 1.59e-4 ✓ sig.
pre-B cell allelic exclusion
RAG1, RAG2
 GO:0002331 2 / 4 779× 2.27e-6 1.59e-4 ✓ sig.
chromosome organization
INO80, DCLRE1C, LIG4
 GO:0051276 3 / 51 91.6× 4.14e-6 2.58e-4 ✓ sig.
interleukin-7-mediated signaling pathway
IL2RG, IL7R
 GO:0038111 2 / 8 389× 1.06e-5 5.43e-4 ✓ sig.
negative regulation of thymocyte apoptotic process
RAG1, ADA
 GO:0070244 2 / 10 311× 1.70e-5 7.89e-4 ✓ sig.
double-strand break repair
INO80, DCLRE1C, LIG4
 GO:0006302 3 / 87 53.7× 2.08e-5 9.26e-4 ✓ sig.
negative regulation of T cell apoptotic process
RAG1, IL7R
 GO:0070233 2 / 12 260× 2.49e-5 1.06e-3 ✓ sig.
regulation of T cell differentiation
RAG1, ADA
 GO:0045580 2 / 17 183× 5.11e-5 1.83e-3 ✓ sig.
cellular homeostasis
IL2RG, IL7R
 GO:0019725 2 / 23 135× 9.49e-5 2.91e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Combined cellular and humoral immune defects with granulomas Combined immunodeficiency with skin granulomas 0.667 2 8.44e-9 7.20e-8 ✓ sig.
Combined cellular and humoral immune defects with granulomas Combined immunodeficiency with granulomatosis 0.500 2 2.53e-8 2.03e-7 ✓ sig.
Combined immunodeficiency with granulomatosis Combined immunodeficiency with skin granulomas 0.500 2 2.53e-8 2.03e-7 ✓ sig.
Combined immunodeficiency with skin granulomas Omenn syndrome 0.182 2 3.80e-7 2.53e-6 ✓ sig.
Combined cellular and humoral immune defects with granulomas Omenn syndrome 0.182 2 3.80e-7 2.53e-6 ✓ sig.
Combined immunodeficiency with granulomatosis Omenn syndrome 0.167 2 1.14e-6 6.99e-6 ✓ sig.
Combined immunodeficiency with skin granulomas recombinase activating gene 2 deficiency 0.333 1 1.30e-4 3.90e-4 ✓ sig.
recombinase activating gene 2 deficiency Salla disease 0.333 1 1.30e-4 3.90e-4 ✓ sig.
free sialic acid storage disease Salla disease 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Combined immunodeficiency with skin granulomas recombinase activating gene 1 deficiency 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Combined cellular and humoral immune defects with granulomas recombinase activating gene 2 deficiency 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Combined cellular and humoral immune defects with granulomas recombinase activating gene 1 deficiency 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Combined immunodeficiency with granulomatosis recombinase activating gene 2 deficiency 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Combined immunodeficiency with granulomatosis recombinase activating gene 1 deficiency 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Combined immunodeficiency with skin granulomas Salla disease 0.250 1 2.60e-4 6.40e-4 ✓ sig.
Combined cellular and humoral immune defects with granulomas Salla disease 0.250 1 2.60e-4 6.40e-4 ✓ sig.
Combined immunodeficiency with granulomatosis Salla disease 0.200 1 3.90e-4 8.52e-4 ✓ sig.
Omenn syndrome recombinase activating gene 1 deficiency 0.091 1 6.49e-4 1.22e-3 ✓ sig.
Omenn syndrome recombinase activating gene 2 deficiency 0.091 1 6.49e-4 1.22e-3 ✓ sig.
Omenn syndrome severe combined immunodeficiency due to DCLRE1C deficiency 0.091 1 6.49e-4 1.22e-3 ✓ sig.