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 373

7 diseases · 11 shared-gene connections
7 Diseases
47 Unique genes
0.149 Avg. similarity score
Hemophagocytic lymphohistiocytosis Most-connected disease (5 links)
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Disease Searched: Hemophagocytic lymphohistiocytosis, familial, 2 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 ⇵
Hemophagocytic lymphohistiocytosis 5 5 9
Hereditary hemophagocytic lymphohistiocytosis 5 5 4
Autoinflammatory syndrome 3 3 39
Hemophagocytic lymphohistiocytosis, familial, 2 3 3 1
Hemophagocytic lymphohistiocytosis, familial, 5, with or without microvillus inclusion disease 3 3 1
Congenital lactic acidosis 2 2 4
Immune dysregulation and systemic hyperinflammation syndrome 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
STXBP2 5 / 7 Autoinflammatory syndrome, Congenital lactic acidosis, Hemophagocytic lymphohistiocytosis, Hemophagocytic lymphohistiocytosis, familial, 5, with or without microvillus inclusion disease and 1 more
PRF1 4 / 7 Autoinflammatory syndrome, Hemophagocytic lymphohistiocytosis, Hemophagocytic lymphohistiocytosis, familial, 2, Hereditary hemophagocytic lymphohistiocytosis
STX11 3 / 7 Autoinflammatory syndrome, Hemophagocytic lymphohistiocytosis, Hereditary hemophagocytic lymphohistiocytosis
UNC13D 3 / 7 Autoinflammatory syndrome, Hemophagocytic lymphohistiocytosis, Hereditary hemophagocytic lymphohistiocytosis
RC3H1 2 / 7 Hemophagocytic lymphohistiocytosis, Immune dysregulation and systemic hyperinflammation syndrome
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 ⇵
NOD-like receptor signaling pathway
MEFV, NLRC4, NLRP12, NLRP3, NOD2, PSTPIP1, STING1, XIAP, TNFAIP3
 KEGG 9 / 187 12.3× 3.63e-8 2.03e-6 ✓ sig.
Regulation of TNFR1 signaling
TNFRSF1A, XIAP, TNFAIP3, OTULIN
 Reactome 4 / 33 31.0× 7.75e-6 2.09e-4 ✓ sig.
The NLRP3 inflammasome
MEFV, NLRP3, PSTPIP1
 Reactome 3 / 15 51.1× 2.47e-5 5.51e-4 ✓ sig.
Cholesterol biosynthesis
HMGCR, MVK, PMVK
 Reactome 3 / 21 36.5× 7.11e-5 1.31e-3 ✓ sig.
Terpenoid backbone biosynthesis
HMGCR, MVK, PMVK
 KEGG 3 / 23 33.3× 9.42e-5 1.64e-3 ✓ sig.
Purinergic signaling in leishmaniasis infection
MEFV, NLRP3, PSTPIP1
 Reactome 3 / 24 31.9× 1.07e-4 1.82e-3 ✓ sig.
Yersinia infection
MEFV, NLRC4, NLRP3, RHOG, CDC42
 KEGG 5 / 138 9.3× 1.94e-4 2.92e-3 ✓ sig.
TNFR1-induced NFkappaB signaling pathway
TNFRSF1A, XIAP, TNFAIP3
 Reactome 3 / 30 25.6× 2.12e-4 3.14e-3 ✓ sig.
Activation of gene expression by SREBF (SREBP)
HMGCR, MVK, PMVK
 Reactome 3 / 42 18.3× 5.79e-4 6.95e-3 ✓ sig.
NF-kappa B signaling pathway
CARD14, TNFRSF1A, XIAP, TNFAIP3
 KEGG 4 / 105 9.7× 7.37e-4 8.36e-3 ✓ sig.
RHO GTPases activate KTN1
RHOG, CDC42
 Reactome 2 / 11 46.5× 8.06e-4 8.96e-3 ✓ sig.
TNFR1-induced proapoptotic signaling
TNFRSF1A, TNFAIP3
 Reactome 2 / 13 39.3× 1.14e-3 1.16e-2 ✓ sig.
TNF signaling pathway
NOD2, TNFRSF1A, XIAP, TNFAIP3
 KEGG 4 / 119 8.6× 1.18e-3 1.19e-2 ✓ sig.
Neutrophil degranulation
ADA2, ELANE, RAB27A, STING1, UNC13D, RHOG, FGL2
 Reactome 7 / 480 3.7× 2.45e-3 2.08e-2 ✓ sig.
Salmonella infection
NLRC4, NLRP3, TNFRSF1A, RHOG, CDC42
 KEGG 5 / 248 5.2× 2.73e-3 2.24e-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 ⇵
pattern recognition receptor signaling pathway
MEFV, NLRC4, NLRP3, NOD2, STING1
 GO:0002221 5 / 21 94.7× 1.60e-9 3.25e-7 ✓ sig.
negative regulation of inflammatory response
ELANE, MEFV, MVK, NLRP12, NLRP3, TNFRSF1A, TNFAIP3, OTULIN
 GO:0050728 8 / 152 20.9× 3.83e-9 7.09e-7 ✓ sig.
positive regulation of non-canonical NF-kappaB signal transduction
CD27, NLRP12, NLRP3, NOD2, RC3H1, HAVCR2
 GO:1901224 6 / 66 36.1× 1.47e-8 2.31e-6 ✓ sig.
inflammatory response
AP3B1, IL1RN, IL36RN, MEFV, NLRC4, NLRP3, PSTPIP1, TNFRSF1A, TNFAIP3, HAVCR2
 GO:0006954 10 / 467 8.5× 1.95e-7 2.07e-5 ✓ sig.
regulation of inflammatory response
MEFV, NLRP12, NLRP3, NOD2, STING1, XIAP
 GO:0050727 6 / 106 22.5× 2.57e-7 2.60e-5 ✓ sig.
immune system process
IL36RN, ITK, MEFV, NLRC4, NLRP3, NOD2, PSMB8, PSTPIP1, SH2D1A, STING1, TNFAIP3, HAVCR2
 GO:0002376 13 / 943 5.5× 3.60e-7 3.44e-5 ✓ sig.
positive regulation of interleukin-1 beta production
MEFV, NLRC4, NLRP12, NLRP3, NOD2
 GO:0032731 5 / 66 30.1× 6.44e-7 5.60e-5 ✓ sig.
innate immune response
IL36RN, MEFV, NLRC4, NLRP3, NOD2, PSTPIP1, SH2D1A, STING1, HAVCR2, OTULIN
 GO:0045087 10 / 605 6.6× 2.06e-6 1.45e-4 ✓ sig.
pigmentation
AP3B1, BLOC1S6, LYST, RAB27A
 GO:0043473 4 / 39 40.8× 2.71e-6 1.80e-4 ✓ sig.
pyroptotic inflammatory response
ELANE, MEFV, NLRC4, NLRP3
 GO:0070269 4 / 40 39.8× 3.00e-6 1.95e-4 ✓ sig.
nucleotide-binding oligomerization domain containing 2 signaling pathway
NOD2, XIAP, OTULIN
 GO:0070431 3 / 14 85.2× 5.32e-6 3.09e-4 ✓ sig.
positive regulation of inflammatory response
MEFV, NLRC4, NLRP12, NLRP3, TNFRSF1A
 GO:0050729 5 / 122 16.3× 1.35e-5 6.41e-4 ✓ sig.
defense response to bacterium
ELANE, LYST, NLRC4, NOD2, TNFRSF1A, XIAP
 GO:0042742 6 / 214 11.1× 1.53e-5 7.06e-4 ✓ sig.
isopentenyl diphosphate biosynthetic process, mevalonate pathway
MVK, PMVK
 GO:0019287 2 / 3 265× 1.85e-5 8.18e-4 ✓ sig.
leukocyte mediated cytotoxicity
PRF1, STXBP2
 GO:0001909 2 / 3 265× 1.85e-5 8.18e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hemophagocytic lymphohistiocytosis Hereditary hemophagocytic lymphohistiocytosis 0.400 4 5.26e-14 6.04e-13 ✓ sig.
Autoinflammatory syndrome Hereditary hemophagocytic lymphohistiocytosis 0.100 4 3.43e-11 3.33e-10 ✓ sig.
Autoinflammatory syndrome Hemophagocytic lymphohistiocytosis 0.089 4 4.29e-9 3.53e-8 ✓ sig.
Congenital lactic acidosis Hemophagocytic lymphohistiocytosis, familial, 5, with or without microvillus inclusion disease 0.200 1 2.58e-4 5.39e-4 ✓ sig.
Hemophagocytic lymphohistiocytosis, familial, 2 Hereditary hemophagocytic lymphohistiocytosis 0.200 1 2.58e-4 5.39e-4 ✓ sig.
Hemophagocytic lymphohistiocytosis, familial, 5, with or without microvillus inclusion disease Hereditary hemophagocytic lymphohistiocytosis 0.200 1 2.58e-4 5.39e-4 ✓ sig.
Hemophagocytic lymphohistiocytosis Hemophagocytic lymphohistiocytosis, familial, 2 0.100 1 5.81e-4 1.00e-3 ✓ sig.
Hemophagocytic lymphohistiocytosis Hemophagocytic lymphohistiocytosis, familial, 5, with or without microvillus inclusion disease 0.100 1 5.81e-4 1.00e-3 ✓ sig.
Hemophagocytic lymphohistiocytosis Immune dysregulation and systemic hyperinflammation syndrome 0.100 1 5.81e-4 1.00e-3 ✓ sig.
Congenital lactic acidosis Hereditary hemophagocytic lymphohistiocytosis 0.125 1 1.03e-3 1.57e-3 ✓ sig.
Autoinflammatory syndrome Hemophagocytic lymphohistiocytosis, familial, 2 0.025 1 2.52e-3 3.27e-3 ✓ sig.