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 80

13 diseases · 21 shared-gene connections
13 Diseases
131 Unique genes
0.122 Avg. similarity score
Endocrine system disease Most-connected disease (7 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 ⇵
Endocrine system disease 7 7 14
Hepatic insufficiency 7 7 9
Autoinflammatory disease, familial, behcet-like 3 5 5 2
Mucocutaneous ulceration 5 5 1
combined immunodeficiency due to RELA haploinsufficiency 5 5 1
Cystitis 3 3 15
Urethral obstruction 3 3 26
Pancreatic ductal carcinoma 2 2 31
Aminoaciduria 1 1 1
Hepatomegaly 1 1 58
Prader-willi-like syndrome 1 1 1
multiple congenital anomalies-hypotonia-seizures syndrome 1 1 1 1
syndromic multisystem autoimmune disease due to ITCH deficiency 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
RELA 9 / 13 Autoinflammatory disease, familial, behcet-like 3, combined immunodeficiency due to RELA haploinsufficiency, Cystitis, Endocrine system disease and 5 more
NFE2L2 4 / 13 Endocrine system disease, Hepatic insufficiency, Hepatomegaly, Pancreatic ductal carcinoma
NOS2 3 / 13 Hepatic insufficiency, Hepatomegaly, Urethral obstruction
NOS3 3 / 13 Hepatic insufficiency, Hepatomegaly, Urethral obstruction
TGFB1 3 / 13 Hepatic insufficiency, Hepatomegaly, Urethral obstruction
ALB 2 / 13 Hepatic insufficiency, Hepatomegaly
CLTRN 2 / 13 Aminoaciduria, Urethral obstruction
CPE 2 / 13 Endocrine system disease, Prader-willi-like syndrome
CXCL11 2 / 13 Cystitis, Pancreatic ductal carcinoma
CYGB 2 / 13 Hepatic insufficiency, Hepatomegaly
HES1 2 / 13 Pancreatic ductal carcinoma, Urethral obstruction
HEY1 2 / 13 Pancreatic ductal carcinoma, Urethral obstruction
HEY2 2 / 13 Pancreatic ductal carcinoma, Urethral obstruction
ITCH 2 / 13 Endocrine system disease, syndromic multisystem autoimmune disease due to ITCH deficiency
KEAP1 2 / 13 Hepatic insufficiency, Hepatomegaly
MAPK14 2 / 13 Hepatic insufficiency, Hepatomegaly
MTOR 2 / 13 Endocrine system disease, Hepatomegaly
PIGN 2 / 13 Endocrine system disease, multiple congenital anomalies-hypotonia-seizures syndrome 1
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
RELA, AGTR1, CDKN2A, HES1, HEY1, HEY2, JAG1, JAG2, KITLG, KRAS, NFE2L2, NOTCH1
 KEGG 31 / 533 5.3× 8.57e-15 2.71e-12 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
RELA, AGTR1, KRAS, VEGFA, MAPK14, NOS3, TGFB1, AKT1, AGT, CCL2, COL3A1, EDN1
 KEGG 16 / 101 14.5× 1.15e-14 3.57e-12 ✓ sig.
Notch signaling pathway
DTX1, DTX4, HES1, HEY1, HEY2, JAG1, JAG2, NOTCH1, NOTCH3, NOTCH4, ITCH
 KEGG 11 / 62 16.3× 5.39e-11 8.22e-9 ✓ sig.
Endocrine resistance
CDKN2A, JAG1, JAG2, KRAS, NOTCH1, NOTCH3, NOTCH4, GNAS, MTOR, MAPK14, AKT1, GPER1
 KEGG 12 / 99 11.1× 7.04e-10 8.18e-8 ✓ sig.
Lipid and atherosclerosis
RELA, HSPA1A, HSPA1B, KRAS, MAP3K7, NFE2L2, MAPK14, NOS3, AKT1, CAMK2A, CYBA, CYP1A1
 KEGG 15 / 216 6.4× 1.24e-8 1.05e-6 ✓ sig.
Relaxin signaling pathway
RELA, KRAS, VEGFA, GNAS, MAPK14, NOS2, NOS3, TGFB1, AKT1, ACTA2, COL3A1, EDN1
 KEGG 12 / 130 8.5× 1.65e-8 1.35e-6 ✓ sig.
NOTCH4 Intracellular Domain Regulates Transcription
HES1, HEY1, HEY2, NOTCH1, NOTCH4, ACTA2
 Reactome 6 / 17 32.4× 1.68e-8 1.37e-6 ✓ sig.
Activated NOTCH1 Transmits Signal to the Nucleus
DTX1, DTX4, JAG2, NOTCH1, ITCH
 Reactome 5 / 10 45.8× 3.45e-8 2.57e-6 ✓ sig.
Apelin signaling pathway
AGTR1, JAG1, KRAS, NOTCH3, MTOR, NOS2, NOS3, AKT1, ACTA2, CDH1, SERPINE1, SMAD3
 KEGG 12 / 140 7.9× 3.80e-8 2.80e-6 ✓ sig.
Fluid shear stress and atherosclerosis
RELA, MAP3K7, NFE2L2, VEGFA, KEAP1, MAPK14, NOS3, AKT1, CYBA, CCL2, EDN1, NPPC
 KEGG 12 / 141 7.8× 4.12e-8 3.00e-6 ✓ sig.
Diabetic cardiomyopathy
RELA, AGTR1, MTOR, MAPK14, NOS3, TGFB1, AKT1, CAMK2A, CYBA, PPARA, AGT, COL3A1
 KEGG 14 / 205 6.3× 4.84e-8 3.47e-6 ✓ sig.
Cellular senescence
RELA, CDKN2A, KRAS, MTOR, SIRT1, MAPK14, TGFB1, AKT1, HIPK2, SERPINE1, SMAD3, TGFB2
 KEGG 12 / 157 7.0× 1.36e-7 8.53e-6 ✓ sig.
Pancreatic cancer
RELA, CDKN2A, KRAS, VEGFA, MTOR, TGFB1, AKT1, SMAD3, TGFB2
 KEGG 9 / 77 10.7× 1.43e-7 8.91e-6 ✓ sig.
HIF-1 signaling pathway
RELA, VEGFA, MTOR, NOS2, NOS3, AKT1, CAMK2A, EDN1, NPPA, SERPINE1
 KEGG 10 / 110 8.3× 3.14e-7 1.78e-5 ✓ sig.
Toxoplasmosis
RELA, HSPA1A, HSPA1B, MAP3K7, MAPK14, NOS2, TGFB1, AKT1, LDLR, TGFB2
 KEGG 10 / 112 8.2× 3.72e-7 2.08e-5 ✓ 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 gene expression
RELA, CDKN2A, DNMT1, HES1, HSPA1A, HSPA1B, KRAS, NFE2L2, NOTCH1, VEGFA, NGF, MAPK14
 GO:0010628 24 / 504 6.8× 9.78e-14 5.37e-11 ✓ sig.
Notch signaling pathway
DTX1, DTX4, HES1, HEY1, HEY2, JAG1, JAG2, NOTCH1, NOTCH3, NOTCH4, TGFB1, NR1H4
 GO:0007219 13 / 117 15.8× 1.80e-12 7.77e-10 ✓ sig.
aortic valve morphogenesis
HEY1, HEY2, JAG1, NOTCH1, NOS3, TGFB1, ADAMTS5, NPPA, SNAI1
 GO:0003180 9 / 37 34.7× 3.26e-12 1.33e-9 ✓ sig.
positive regulation of transcription by RNA polymerase II
RELA, CDKN2A, HES1, HEY1, HEY2, JAG1, NFE2L2, NOTCH1, NOTCH3, NOTCH4, OSM, VEGFA
 GO:0045944 33 / 1,208 3.9× 7.94e-12 2.98e-9 ✓ sig.
regulation of cell population proliferation
AGTR1, CXCL11, DNMT1, JAG1, JAG2, NOTCH1, CXCL10, CXCL9, SIRT1, NOS2, TGFB1, NR5A2
 GO:0042127 15 / 201 10.6× 1.13e-11 4.12e-9 ✓ sig.
pulmonary valve morphogenesis
HEY1, HEY2, JAG1, NOTCH1, NOS3, ADAMTS5, TGFB2
 GO:0003184 7 / 18 55.5× 2.11e-11 7.14e-9 ✓ sig.
response to hypoxia
MAP3K7, VEGFA, CYGB, NOS2, TGFB1, CYBA, CYP1A1, LEP, PPARA, EDN1, NPPA, NPPC
 GO:0001666 14 / 176 11.3× 2.41e-11 8.02e-9 ✓ sig.
negative regulation of gene expression
DNMT1, HES1, HEY2, MAP3K7, NOTCH1, VEGFA, SIRT1, NOS2, TGFB1, AKT1, GPER1, IFNA2
 GO:0010629 18 / 339 7.6× 2.67e-11 8.79e-9 ✓ sig.
cellular response to tumor necrosis factor
RELA, HES1, MAP3K7, NFE2L2, SIRT1, MAPK14, AKT1, CYBA, GPER1, CCL2, EDN1
 GO:0071356 11 / 107 14.7× 2.30e-10 6.05e-8 ✓ sig.
negative regulation of cell growth
SIPA1, CDKN2A, HSPA1A, HSPA1B, STK11, TGFB1, SESN2, NPPA, NPPB, SMAD3, TGFB2
 GO:0030308 11 / 115 13.6× 5.04e-10 1.22e-7 ✓ sig.
inflammatory response
RELA, AGTR1, CXCL11, MAP3K7, NFE2L2, TLR5, CXCL10, CXCL9, ITCH, MTOR, NOS2, TGFB1
 GO:0006954 19 / 467 5.8× 6.71e-10 1.57e-7 ✓ sig.
negative regulation of transcription by RNA polymerase II
RELA, CDKN2A, DNMT1, HES1, HEY1, HEY2, HSPA1A, NOTCH1, NOTCH3, NOTCH4, VEGFA, YEATS2
 GO:0000122 27 / 1,002 3.8× 1.24e-9 2.71e-7 ✓ sig.
negative regulation of biomineral tissue development
HEY1, HEY2, NOTCH1, NOS3, TGFB1
 GO:0070168 5 / 10 71.3× 3.84e-9 7.39e-7 ✓ sig.
blood vessel diameter maintenance
AGTR1, NOS3, AGT, EDN1, NPPA, NPPB, NPPC
 GO:0097746 7 / 37 27.0× 6.12e-9 1.12e-6 ✓ sig.
intracellular receptor signaling pathway
AHR, NR1H2, NR1H4, NR1I2, NR1I3, NR5A2, PPARA
 GO:0030522 7 / 39 25.6× 9.03e-9 1.57e-6 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hepatic insufficiency Hepatomegaly 0.153 9 7.96e-23 1.81e-21 ✓ sig.
Hepatic insufficiency Urethral obstruction 0.125 4 8.00e-10 7.72e-9 ✓ sig.
Pancreatic ductal carcinoma Urethral obstruction 0.074 4 1.95e-7 1.37e-6 ✓ sig.
Endocrine system disease Hepatic insufficiency 0.091 2 2.75e-5 1.35e-4 ✓ sig.
combined immunodeficiency due to RELA haploinsufficiency Mucocutaneous ulceration 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Autoinflammatory disease, familial, behcet-like 3 Mucocutaneous ulceration 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Autoinflammatory disease, familial, behcet-like 3 combined immunodeficiency due to RELA haploinsufficiency 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Hepatic insufficiency Pancreatic ductal carcinoma 0.051 2 1.40e-4 4.19e-4 ✓ sig.
combined immunodeficiency due to RELA haploinsufficiency Hepatic insufficiency 0.100 1 5.84e-4 1.14e-3 ✓ sig.
Hepatic insufficiency Mucocutaneous ulceration 0.100 1 5.84e-4 1.14e-3 ✓ sig.
combined immunodeficiency due to RELA haploinsufficiency Endocrine system disease 0.067 1 9.09e-4 1.56e-3 ✓ sig.
Endocrine system disease Mucocutaneous ulceration 0.067 1 9.09e-4 1.56e-3 ✓ sig.
Endocrine system disease multiple congenital anomalies-hypotonia-seizures syndrome 1 0.067 1 9.09e-4 1.56e-3 ✓ sig.
Endocrine system disease Prader-willi-like syndrome 0.067 1 9.09e-4 1.56e-3 ✓ sig.
Endocrine system disease syndromic multisystem autoimmune disease due to ITCH deficiency 0.067 1 9.09e-4 1.56e-3 ✓ sig.
combined immunodeficiency due to RELA haploinsufficiency Cystitis 0.063 1 9.74e-4 1.64e-3 ✓ sig.
Cystitis Mucocutaneous ulceration 0.063 1 9.74e-4 1.64e-3 ✓ sig.
Autoinflammatory disease, familial, behcet-like 3 Hepatic insufficiency 0.091 1 1.17e-3 1.88e-3 ✓ sig.
Aminoaciduria Urethral obstruction 0.037 1 1.69e-3 2.51e-3 ✓ sig.
Autoinflammatory disease, familial, behcet-like 3 Endocrine system disease 0.063 1 1.82e-3 2.66e-3 ✓ sig.
Autoinflammatory disease, familial, behcet-like 3 Cystitis 0.059 1 1.95e-3 2.81e-3 ✓ sig.