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 135

10 diseases · 15 shared-gene connections
10 Diseases
151 Unique genes
0.088 Avg. similarity score
Cholelithiasis Most-connected disease (5 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 ⇵
Cholelithiasis 5 5 139
Intrahepatic cholestasis 5 5 9
Progressive intrahepatic cholestasis 5 5 13
Intrahepatic cholestasis of pregnancy 4 4 20
Benign recurrent intrahepatic cholestasis 3 3 2
progressive familial intrahepatic cholestasis type 3 3 3 1
mednik syndrome 2 2 1
Hyperbiliverdinemia 1 1 1
Peliosis hepatis 1 1 1
hyperphenylalaninemia due to DNAJC12 deficiency 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
ABCB11 5 / 10 Benign recurrent intrahepatic cholestasis, Cholelithiasis, Intrahepatic cholestasis, Intrahepatic cholestasis of pregnancy and 1 more
ABCB4 5 / 10 Cholelithiasis, Intrahepatic cholestasis, Intrahepatic cholestasis of pregnancy, progressive familial intrahepatic cholestasis type 3 and 1 more
ATP8B1 5 / 10 Benign recurrent intrahepatic cholestasis, Cholelithiasis, Intrahepatic cholestasis, Intrahepatic cholestasis of pregnancy and 1 more
AP1S1 3 / 10 Cholelithiasis, Intrahepatic cholestasis, mednik syndrome
NR1H4 3 / 10 Cholelithiasis, Intrahepatic cholestasis of pregnancy, Progressive intrahepatic cholestasis
TJP2 3 / 10 Cholelithiasis, Intrahepatic cholestasis, Progressive intrahepatic cholestasis
BLVRA 2 / 10 Cholelithiasis, Hyperbiliverdinemia
CYP7A1 2 / 10 Cholelithiasis, Intrahepatic cholestasis of pregnancy
DNAJC12 2 / 10 Cholelithiasis, hyperphenylalaninemia due to DNAJC12 deficiency
EGR1 2 / 10 Cholelithiasis, Intrahepatic cholestasis
F2RL3 2 / 10 Cholelithiasis, Peliosis hepatis
HSD3B7 2 / 10 Cholelithiasis, Intrahepatic cholestasis
KIF12 2 / 10 Cholelithiasis, Progressive intrahepatic cholestasis
MAF 2 / 10 Cholelithiasis, Intrahepatic cholestasis
MAFG 2 / 10 Cholelithiasis, Intrahepatic cholestasis
MYO5B 2 / 10 Cholelithiasis, Progressive intrahepatic cholestasis
SEMA7A 2 / 10 Cholelithiasis, Progressive intrahepatic cholestasis
SERPINA1 2 / 10 Cholelithiasis, Intrahepatic cholestasis of pregnancy
SLC10A1 2 / 10 Cholelithiasis, Intrahepatic cholestasis of pregnancy
SLC51A 2 / 10 Cholelithiasis, Progressive intrahepatic cholestasis
TNF 2 / 10 Cholelithiasis, Intrahepatic cholestasis of pregnancy
USP53 2 / 10 Cholelithiasis, Progressive intrahepatic cholestasis
VCAM1 2 / 10 Cholelithiasis, Intrahepatic cholestasis of pregnancy
VPS33B 2 / 10 Cholelithiasis, Progressive intrahepatic cholestasis
ZFYVE19 2 / 10 Cholelithiasis, Progressive intrahepatic cholestasis
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 ⇵
AGE-RAGE signaling pathway in diabetic complications
AGT, CXCL8, EGR1, ICAM1, IL6, MAPK13, MAPK14, RELA, SERPINE1, TNF, VCAM1, COL1A1
 KEGG 22 / 101 17.3× 1.30e-21 1.35e-18 ✓ sig.
Lipid and atherosclerosis
CXCL2, CXCL8, CYP2B6, ICAM1, IL6, LY96, MAPK13, MAPK14, NFE2L2, RELA, TLR2, TNF
 KEGG 25 / 216 9.2× 1.90e-17 9.75e-15 ✓ sig.
Chagas disease
CXCL8, IL6, MAPK13, MAPK14, NOS2, RELA, SERPINE1, TLR2, TNF, FOS, IL1B, JUN
 KEGG 19 / 103 14.7× 2.44e-17 1.23e-14 ✓ sig.
Pertussis
CXCL8, IL6, LY96, MAPK13, MAPK14, NOS2, RELA, TNF, FOS, IL1B, JUN, MAPK1
 KEGG 17 / 78 17.3× 6.38e-17 2.99e-14 ✓ sig.
Toll-like receptor signaling pathway
CXCL8, IL6, LY96, MAPK13, MAPK14, RELA, TLR2, TNF, FOS, IL1B, JUN, MAP3K7
 KEGG 18 / 109 13.1× 1.38e-15 5.22e-13 ✓ sig.
IL-17 signaling pathway
CCL7, CXCL2, CXCL8, IL6, MAPK13, MAPK14, RELA, TNF, FOS, IL1B, JUN, MAP3K7
 KEGG 17 / 94 14.4× 1.81e-15 6.70e-13 ✓ sig.
Relaxin signaling pathway
ADCY9, MAPK13, MAPK14, NOS2, RELA, ACTA2, COL1A1, COL3A1, FOS, JUN, MAPK1, MAPK3
 KEGG 18 / 130 11.0× 3.40e-14 9.47e-12 ✓ sig.
Leishmaniasis
MAPK13, MAPK14, NOS2, RELA, TLR2, TNF, FOS, IL1B, JUN, MAP3K7, MAPK1, MAPK3
 KEGG 15 / 78 15.3× 3.39e-14 9.47e-12 ✓ sig.
TNF signaling pathway
CXCL2, ICAM1, IL6, MAPK13, MAPK14, RELA, TNF, VCAM1, FOS, IL1B, JUN, MAP3K7
 KEGG 17 / 119 11.4× 1.07e-13 2.72e-11 ✓ sig.
Fluid shear stress and atherosclerosis
ICAM1, MAPK13, MAPK14, NFE2L2, NQO1, RELA, TNF, VCAM1, FOS, IL1B, JUN, KEAP1
 KEGG 18 / 141 10.2× 1.44e-13 3.55e-11 ✓ sig.
Hepatitis B
CXCL8, IL6, MAPK13, MAPK14, RELA, SLC10A1, TLR2, TNF, FOS, JUN, MAP3K7, MAPK1
 KEGG 19 / 163 9.3× 1.57e-13 3.83e-11 ✓ sig.
Activation of the AP-1 family of transcription factors
MAPK14, FOS, JUN, MAPK1, MAPK3, MAPK8, MAPK9
 Reactome 7 / 10 55.7× 5.02e-12 9.52e-10 ✓ sig.
Bile secretion
ABCB11, ABCB4, ABCC2, ABCC3, ADCY9, CYP7A1, NR1H4, SLC10A1, SLC51A, SLC51B, SLCO1A2, ABCB1
 KEGG 14 / 90 12.4× 5.34e-12 1.01e-9 ✓ sig.
Toxoplasmosis
LY96, MAPK13, MAPK14, NOS2, RELA, TLR2, TNF, MAP3K7, MAPK1, MAPK3, MAPK8, MAPK9
 KEGG 15 / 112 10.7× 8.47e-12 1.54e-9 ✓ sig.
Yersinia infection
CXCL8, IL6, MAPK13, MAPK14, RELA, TNF, FOS, IL1B, JUN, MAP3K7, MAPK1, MAPK3
 KEGG 16 / 138 9.2× 1.57e-11 2.69e-9 ✓ 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 ⇵
response to lipopolysaccharide
BLVRA, CNR2, LY96, MAPK14, NOS2, NQO1, RELA, TNF, VCAM1, FOS, IL1B, MAPK1
 GO:0032496 18 / 161 13.8× 8.83e-16 6.94e-13 ✓ sig.
cellular response to lipopolysaccharide
CXCL8, IL6, LY96, MAPK14, NOS2, NR1H3, NR1H4, RELA, SERPINE1, TNF, CD68, HMGB1
 GO:0071222 18 / 187 11.9× 1.26e-14 8.05e-12 ✓ sig.
bile acid and bile salt transport
ATP8B1, ABCB11, ABCC2, ABCC3, NR1H4, SLC10A1, SLC51A, SLC51B, SLCO1A2
 GO:0015721 9 / 26 42.8× 3.21e-13 1.63e-10 ✓ sig.
positive regulation of gene expression
CXCL8, EGR1, ID4, IGF1, IL6, MAPK14, NFE2L2, NR1H2, RDX, RELA, TLR2, TNF
 GO:0010628 23 / 504 5.6× 1.75e-11 6.06e-9 ✓ sig.
positive regulation of miRNA transcription
AGT, EGR1, IL6, NR1H2, RELA, TNF, WT1, FOS, JUN, TGFB1
 GO:1902895 10 / 56 22.1× 2.28e-11 7.60e-9 ✓ sig.
inflammatory response
BLVRA, CCL7, CNR2, CXCL2, CXCL8, IL6, LY96, NFE2L2, NOS2, NR1H4, RELA, TLR2
 GO:0006954 22 / 467 5.8× 2.72e-11 8.91e-9 ✓ sig.
positive regulation of interleukin-8 production
IL6, NOS2, RELA, SERPINE1, TLR2, TNF, HMGB1, IL1B, MYD88, TLR4
 GO:0032757 10 / 65 19.0× 1.08e-10 3.07e-8 ✓ sig.
stress-activated MAPK cascade
MAPK13, MAPK14, MAP3K7, MAPK1, MAPK3, MAPK8, TLR4
 GO:0051403 7 / 23 37.7× 4.30e-10 1.05e-7 ✓ sig.
lipopolysaccharide-mediated signaling pathway
LY96, MAPK14, TLR2, MAPK1, MAPK3, MYD88, NOS3, TLR4
 GO:0031663 8 / 38 26.1× 6.01e-10 1.43e-7 ✓ sig.
positive regulation of interleukin-6 production
IL6, MAPK13, NOS2, RELA, TLR2, TNF, HMGB1, IL1B, MYD88, TGFB1, TLR4
 GO:0032755 11 / 103 13.2× 7.01e-10 1.63e-7 ✓ sig.
positive regulation of ERK1 and ERK2 cascade
FGA, ICAM1, IGF1, SLC30A10, TNF, ACTA2, CCN2, HMGB1, IL1B, JUN, MAPK3, TGFB1
 GO:0070374 14 / 201 8.6× 9.56e-10 2.16e-7 ✓ sig.
cellular response to tumor necrosis factor
CXCL8, MAPK14, NFE2L2, RELA, VCAM1, COL1A1, FOS, MAP3K7, MAPK1, MAPK3, ABCB1
 GO:0071356 11 / 107 12.7× 1.06e-9 2.35e-7 ✓ sig.
positive regulation of chemokine production
EGR1, IL6, TLR2, TNF, HMGB1, IL1B, MYD88, TLR4
 GO:0032722 8 / 49 20.2× 5.14e-9 9.55e-7 ✓ sig.
response to ethanol
CAT, CYP7A1, RELA, SLC10A1, TNF, VCAM1, CD68, FOS, MYD88, TGFB1
 GO:0045471 10 / 110 11.3× 2.07e-8 3.21e-6 ✓ sig.
JNK cascade
TNF, IL1B, JUN, MAP3K7, MAPK8, MAPK9, MYD88, TLR4
 GO:0007254 8 / 61 16.2× 3.09e-8 4.51e-6 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Cholelithiasis Progressive intrahepatic cholestasis 0.085 12 2.33e-24 5.77e-23 ✓ sig.
Intrahepatic cholestasis Progressive intrahepatic cholestasis 0.211 4 3.84e-11 4.20e-10 ✓ sig.
Intrahepatic cholestasis of pregnancy Progressive intrahepatic cholestasis 0.133 4 1.47e-9 1.39e-8 ✓ sig.
Intrahepatic cholestasis Intrahepatic cholestasis of pregnancy 0.111 3 1.57e-7 1.12e-6 ✓ sig.
Benign recurrent intrahepatic cholestasis Intrahepatic cholestasis 0.200 2 3.04e-7 2.06e-6 ✓ sig.
Benign recurrent intrahepatic cholestasis Progressive intrahepatic cholestasis 0.143 2 6.58e-7 4.21e-6 ✓ sig.
Benign recurrent intrahepatic cholestasis Intrahepatic cholestasis of pregnancy 0.095 2 1.60e-6 9.62e-6 ✓ sig.
Intrahepatic cholestasis mednik syndrome 0.100 1 5.84e-4 1.14e-3 ✓ sig.
Intrahepatic cholestasis progressive familial intrahepatic cholestasis type 3 0.100 1 5.84e-4 1.14e-3 ✓ sig.
progressive familial intrahepatic cholestasis type 3 Progressive intrahepatic cholestasis 0.071 1 8.44e-4 1.48e-3 ✓ sig.
Intrahepatic cholestasis of pregnancy progressive familial intrahepatic cholestasis type 3 0.048 1 1.30e-3 2.04e-3 ✓ sig.
Cholelithiasis Hyperbiliverdinemia 0.007 1 9.03e-3 1.03e-2 ✓ sig.
Cholelithiasis hyperphenylalaninemia due to DNAJC12 deficiency 0.007 1 9.03e-3 1.03e-2 ✓ sig.
Cholelithiasis mednik syndrome 0.007 1 9.03e-3 1.03e-2 ✓ sig.
Cholelithiasis Peliosis hepatis 0.007 1 9.03e-3 1.03e-2 ✓ sig.