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 554

5 diseases · 6 shared-gene connections
5 Diseases
95 Unique genes
0.118 Avg. similarity score
Esophageal disease Most-connected disease (4 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 ⇵
Esophageal disease 4 4 30
Esophageal ulcer 3 3 14
Camptodactyly 2 2 1
Hypomagnesemia 5, renal, with ocular involvement 2 2 1
Barrett esophagus 1 1 74

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

Gene ⇵ Member diseases ⇵ Linked diseases
CLDN19 3 / 5 Esophageal disease, Esophageal ulcer, Hypomagnesemia 5, renal, with ocular involvement
TLN2 3 / 5 Camptodactyly, Esophageal disease, Esophageal ulcer
AKTIP 2 / 5 Barrett esophagus, Esophageal disease
ALPK3 2 / 5 Esophageal disease, Esophageal ulcer
ASIC2 2 / 5 Esophageal disease, Esophageal ulcer
ATXN2 2 / 5 Barrett esophagus, Esophageal disease
CLNK 2 / 5 Esophageal disease, Esophageal ulcer
CRTC1 2 / 5 Barrett esophagus, Esophageal disease
HMCN2 2 / 5 Barrett esophagus, Esophageal disease
KLHL26 2 / 5 Barrett esophagus, Esophageal disease
MVB12B 2 / 5 Barrett esophagus, Esophageal disease
NT5C2 2 / 5 Barrett esophagus, Esophageal disease
PBX3 2 / 5 Barrett esophagus, Esophageal disease
RPGRIP1L 2 / 5 Barrett esophagus, Esophageal disease
SAMD5 2 / 5 Esophageal disease, Esophageal ulcer
SASH1 2 / 5 Esophageal disease, Esophageal ulcer
SLC39A8 2 / 5 Barrett esophagus, Esophageal disease
SOD2 2 / 5 Esophageal disease, Esophageal ulcer
SPATS2L 2 / 5 Esophageal disease, Esophageal ulcer
TECTA 2 / 5 Esophageal disease, Esophageal ulcer
TRHDE 2 / 5 Esophageal disease, Esophageal ulcer
WTAP 2 / 5 Esophageal disease, Esophageal ulcer
YBX1 2 / 5 Esophageal disease, Esophageal ulcer
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 ⇵
Scavenging by Class A Receptors
MSR1, APOB, APOE
 Reactome 3 / 11 34.5× 7.56e-5 1.52e-3 ✓ sig.
Abacavir transmembrane transport
SLC22A2, SLC22A3
 Reactome 2 / 3 84.3× 1.85e-4 3.09e-3 ✓ sig.
Interleukin-4 and Interleukin-13 signaling
CXCL8, HGF, MCL1, MMP1, PTGS2, TP53
 Reactome 6 / 108 7.0× 2.09e-4 3.40e-3 ✓ sig.
Transcriptional Regulation by VENTX
RELA, AGO3, TP53, CDKN2A
 Reactome 4 / 38 13.3× 2.21e-4 3.55e-3 ✓ sig.
Bladder cancer
CXCL8, MMP1, TP53, CDKN2A
 KEGG 4 / 41 12.3× 2.97e-4 4.48e-3 ✓ sig.
Chylomicron clearance
APOB, APOE
 Reactome 2 / 5 50.6× 6.10e-4 7.79e-3 ✓ sig.
Lipid and atherosclerosis
CXCL8, MMP1, PPARG, RELA, APOB, SOD2, TP53
 KEGG 7 / 216 4.1× 1.60e-3 1.62e-2 ✓ sig.
Chylomicron remodeling
APOB, APOE
 Reactome 2 / 9 28.1× 2.15e-3 2.01e-2 ✓ sig.
Chylomicron assembly
APOB, APOE
 Reactome 2 / 9 28.1× 2.15e-3 2.01e-2 ✓ sig.
Oncogene Induced Senescence
AGO3, TP53, CDKN2A
 Reactome 3 / 33 11.5× 2.20e-3 2.04e-2 ✓ sig.
Detoxification of Reactive Oxygen Species
GPX3, GPX7, SOD2
 Reactome 3 / 34 11.2× 2.40e-3 2.18e-2 ✓ sig.
Organic cation transport
SLC22A2, SLC22A3
 Reactome 2 / 10 25.3× 2.67e-3 2.35e-2 ✓ sig.
Gastric acid secretion
GAST, SLC9A1, SST, CFTR
 KEGG 4 / 76 6.7× 3.05e-3 2.58e-2 ✓ sig.
Stabilization of p53
TP53, CDKN2A
 Reactome 2 / 11 23.0× 3.25e-3 2.70e-2 ✓ sig.
Longevity regulating pathway
PPARG, RELA, SOD2, TP53
 KEGG 4 / 90 5.6× 5.59e-3 3.93e-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 ⇵
positive regulation of gene expression
CXCL8, MMP12, NR1I2, PPARG, RELA, VDR, AGO3, ALDH1A2, APOB, BCL3, GDF7, CLDN19
 GO:0010628 16 / 504 6.2× 4.80e-9 9.25e-7 ✓ sig.
cellular oxidant detoxification
GPX3, GPX7, PTGS2, MGST1, NNT, APOE
 GO:0098869 6 / 66 17.9× 1.05e-6 8.91e-5 ✓ sig.
liver development
HGF, RELA, ALDH1A2, RPGRIP1L, HNF1B, SOD2
 GO:0001889 6 / 87 13.6× 5.33e-6 3.33e-4 ✓ sig.
response to oxidative stress
GPX3, GPX7, PTGS2, MSRA, APOE, SOD2, TP53
 GO:0006979 7 / 146 9.4× 9.58e-6 5.25e-4 ✓ sig.
negative regulation of apoptotic process
HGF, MCL1, PTGS2, RELA, SLC9A1, BCL3, DUSP1, NNT, ASIC2, HNF1B, SOD2, TP53
 GO:0043066 12 / 524 4.5× 1.37e-5 6.97e-4 ✓ sig.
negative regulation of membrane hyperpolarization
CRTC1, SOD2
 GO:1902631 2 / 2 197× 2.56e-5 1.11e-3 ✓ sig.
response to acidic pH
SLC9A1, SST, ASIC2
 GO:0010447 3 / 12 49.2× 2.71e-5 1.16e-3 ✓ sig.
positive regulation of mitochondrial membrane permeability
SLC9A1, TP53
 GO:0035794 2 / 3 131× 7.65e-5 2.54e-3 ✓ sig.
apoptotic process involved in mammary gland involution
VDR, CDKN2A
 GO:0060057 2 / 3 131× 7.65e-5 2.54e-3 ✓ sig.
cyclooxygenase pathway
CTHRC1, PTGS2
 GO:0019371 2 / 3 131× 7.65e-5 2.54e-3 ✓ sig.
histamine transport
SLC22A2, SLC22A3
 GO:0051608 2 / 3 131× 7.65e-5 2.54e-3 ✓ sig.
negative regulation of cell population proliferation
CDH13, CXCL8, SST, VDR, ALDH1A2, DUSP1, CLDN19, SOD2, TP53, CDKN2A
 GO:0008285 10 / 444 4.4× 8.64e-5 2.77e-3 ✓ sig.
positive regulation of apoptotic process involved in mammary gland involution
VDR, CDKN2A
 GO:0060058 2 / 4 98.4× 1.52e-4 4.19e-3 ✓ sig.
spermidine transmembrane transport
SLC22A2, SLC22A3
 GO:1903711 2 / 4 98.4× 1.52e-4 4.19e-3 ✓ sig.
histamine uptake
SLC22A2, SLC22A3
 GO:0051615 2 / 4 98.4× 1.52e-4 4.19e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Esophageal disease Esophageal ulcer 0.406 13 3.55e-36 7.87e-35 ✓ sig.
Barrett esophagus Esophageal disease 0.106 10 7.94e-17 1.04e-15 ✓ sig.
Camptodactyly Esophageal ulcer 0.067 1 9.04e-4 1.41e-3 ✓ sig.
Esophageal ulcer Hypomagnesemia 5, renal, with ocular involvement 0.067 1 9.04e-4 1.41e-3 ✓ sig.
Camptodactyly Esophageal disease 0.032 1 1.94e-3 2.65e-3 ✓ sig.
Esophageal disease Hypomagnesemia 5, renal, with ocular involvement 0.032 1 1.94e-3 2.65e-3 ✓ sig.