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 174

10 diseases · 16 shared-gene connections
10 Diseases
320 Unique genes
0.099 Avg. similarity score
Obstructive airway disease Most-connected disease (6 links)
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Disease Searched: Lung disease, immunodeficiency, and chromosome breakage syndrome; 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 ⇵
Obstructive airway disease 6 6 100
Cystic fibrosis 5 5 62
Lung disease 5 5 102
Chronic obstructive pulmonary disease 4 4 42
Bronchopulmonary dysplasia 3 3 45
Pulmonary fibrosis 3 3 107
Asbestosis 2 2 17
Susceptibility to respiratory infections associated with CD8alpha chain mutation 2 2 1
Immunodeficiency 97 with autoinflammation 1 1 1
Lung disease, immunodeficiency, and chromosome breakage syndrome; 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
TNF 7 / 10 Asbestosis, Bronchopulmonary dysplasia, Chronic obstructive pulmonary disease, Cystic fibrosis and 3 more
IL1B 6 / 10 Asbestosis, Bronchopulmonary dysplasia, Cystic fibrosis, Lung disease and 2 more
SERPINA1 6 / 10 Asbestosis, Chronic obstructive pulmonary disease, Cystic fibrosis, Lung disease and 2 more
GSTM1 5 / 10 Asbestosis, Bronchopulmonary dysplasia, Cystic fibrosis, Lung disease and 1 more
GSTT1 5 / 10 Asbestosis, Bronchopulmonary dysplasia, Cystic fibrosis, Lung disease and 1 more
TGFB1 5 / 10 Chronic obstructive pulmonary disease, Cystic fibrosis, Lung disease, Obstructive airway disease and 1 more
EPHX1 4 / 10 Asbestosis, Chronic obstructive pulmonary disease, Cystic fibrosis, Obstructive airway disease
HMOX1 4 / 10 Chronic obstructive pulmonary disease, Cystic fibrosis, Obstructive airway disease, Pulmonary fibrosis
MBL2 4 / 10 Bronchopulmonary dysplasia, Cystic fibrosis, Obstructive airway disease, Pulmonary fibrosis
MIF 4 / 10 Chronic obstructive pulmonary disease, Cystic fibrosis, Lung disease, Obstructive airway disease
MMP9 4 / 10 Chronic obstructive pulmonary disease, Lung disease, Obstructive airway disease, Pulmonary fibrosis
PTGS2 4 / 10 Cystic fibrosis, Lung disease, Obstructive airway disease, Pulmonary fibrosis
SFTPA1 4 / 10 Bronchopulmonary dysplasia, Lung disease, Obstructive airway disease, Pulmonary fibrosis
SFTPB 4 / 10 Bronchopulmonary dysplasia, Lung disease, Obstructive airway disease, Pulmonary fibrosis
SFTPD 4 / 10 Bronchopulmonary dysplasia, Chronic obstructive pulmonary disease, Lung disease, Obstructive airway disease
ACE 3 / 10 Lung disease, Obstructive airway disease, Pulmonary fibrosis
ADRB2 3 / 10 Cystic fibrosis, Lung disease, Obstructive airway disease
CD8A 3 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease, Susceptibility to respiratory infections associated with CD8alpha chain mutation
CFTR 3 / 10 Cystic fibrosis, Lung disease, Obstructive airway disease
CXCL2 3 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease, Pulmonary fibrosis
CYP1A1 3 / 10 Chronic obstructive pulmonary disease, Cystic fibrosis, Obstructive airway disease
DSP 3 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease, Pulmonary fibrosis
ELN 3 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease, Pulmonary fibrosis
FAM13A 3 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease, Pulmonary fibrosis
GSTP1 3 / 10 Bronchopulmonary dysplasia, Lung disease, Obstructive airway disease
HIF1A 3 / 10 Chronic obstructive pulmonary disease, Lung disease, Obstructive airway disease
HSPA1A 3 / 10 Cystic fibrosis, Obstructive airway disease, Pulmonary fibrosis
IL13 3 / 10 Lung disease, Obstructive airway disease, Pulmonary fibrosis
IL1RN 3 / 10 Bronchopulmonary dysplasia, Obstructive airway disease, Pulmonary fibrosis
IL6 3 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease, Pulmonary fibrosis
NOS2 3 / 10 Asbestosis, Chronic obstructive pulmonary disease, Obstructive airway disease
NOS3 3 / 10 Chronic obstructive pulmonary disease, Cystic fibrosis, Obstructive airway disease
SFTPC 3 / 10 Lung disease, Obstructive airway disease, Pulmonary fibrosis
SOD3 3 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease, Pulmonary fibrosis
ABCA3 2 / 10 Lung disease, Pulmonary fibrosis
AGER 2 / 10 Chronic obstructive pulmonary disease, Cystic fibrosis
AGTR2 2 / 10 Cystic fibrosis, Lung disease
AP3B1 2 / 10 Lung disease, Pulmonary fibrosis
APIP 2 / 10 Cystic fibrosis, Lung disease
CAT 2 / 10 Lung disease, Pulmonary fibrosis
CCN2 2 / 10 Lung disease, Pulmonary fibrosis
CCR2 2 / 10 Lung disease, Pulmonary fibrosis
CDKN1A 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
CDKN2A 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
CEBPB 2 / 10 Cystic fibrosis, Pulmonary fibrosis
CFD 2 / 10 Asbestosis, Pulmonary fibrosis
CHRM3 2 / 10 Obstructive airway disease, Pulmonary fibrosis
CHRNA3 2 / 10 Lung disease, Obstructive airway disease
CHRNA5 2 / 10 Lung disease, Obstructive airway disease
CRP 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
CSF3 2 / 10 Lung disease, Pulmonary fibrosis
CXCL1 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
CXCL8 2 / 10 Chronic obstructive pulmonary disease, Pulmonary fibrosis
CYP1A2 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
DEFB1 2 / 10 Lung disease, Obstructive airway disease
EDN1 2 / 10 Obstructive airway disease, Pulmonary fibrosis
EDNRA 2 / 10 Cystic fibrosis, Lung disease
EEFSEC 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
EHF 2 / 10 Cystic fibrosis, Lung disease
FOXO3 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
HDAC2 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
HGF 2 / 10 Lung disease, Pulmonary fibrosis
HLA-DPB1 2 / 10 Lung disease, Obstructive airway disease
HSPA1B 2 / 10 Obstructive airway disease, Pulmonary fibrosis
HTR2A 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
ICAM1 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
IL12B 2 / 10 Obstructive airway disease, Pulmonary fibrosis
IL1A 2 / 10 Lung disease, Pulmonary fibrosis
KLF5 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
LCN1 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
MMP14 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
MPO 2 / 10 Cystic fibrosis, Lung disease
MTCL1 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
MUC4 2 / 10 Cystic fibrosis, Lung disease
NAT2 2 / 10 Lung disease, Obstructive airway disease
NFE2L2 2 / 10 Lung disease, Pulmonary fibrosis
NQO1 2 / 10 Lung disease, Obstructive airway disease
NR3C1 2 / 10 Lung disease, Obstructive airway disease
NSMCE3 2 / 10 Lung disease, Lung disease, immunodeficiency, and chromosome breakage syndrome;
PDGFA 2 / 10 Lung disease, Pulmonary fibrosis
PIK3CG 2 / 10 Cystic fibrosis, Immunodeficiency 97 with autoinflammation
PTX3 2 / 10 Cystic fibrosis, Pulmonary fibrosis
RAPGEF3 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
RTEL1 2 / 10 Obstructive airway disease, Pulmonary fibrosis
SCGB1A1 2 / 10 Lung disease, Obstructive airway disease
SCNN1A 2 / 10 Cystic fibrosis, Lung disease
SCNN1B 2 / 10 Cystic fibrosis, Lung disease
SERPINA3 2 / 10 Cystic fibrosis, Obstructive airway disease
SERPINE1 2 / 10 Lung disease, Pulmonary fibrosis
SLC9A3 2 / 10 Cystic fibrosis, Lung disease
SPP1 2 / 10 Asbestosis, Pulmonary fibrosis
TERT 2 / 10 Obstructive airway disease, Pulmonary fibrosis
TLR4 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
TNFRSF8 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
TNFSF8 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
TNNT2 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
TP53 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
TRPV4 2 / 10 Chronic obstructive pulmonary disease, Obstructive airway disease
VDR 2 / 10 Bronchopulmonary dysplasia, Obstructive airway 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 ⇵
Interleukin-4 and Interleukin-13 signaling
IL1B, NOS2, TNF, CDKN1A, FOXO3, HIF1A, HMOX1, ICAM1, IL12B, IL13, IL13RA1, IL6
 Reactome 32 / 108 11.1× 3.86e-25 6.42e-22 ✓ sig.
Interleukin-10 signaling
IL1B, TNF, IL1RN, CD86, CXCL1, CXCL2, ICAM1, IL12B, IL6, PTGS2, TNFRSF1A, CSF3
 Reactome 23 / 47 18.4× 2.53e-24 3.68e-21 ✓ sig.
Pathways in cancer
GSTM1, GSTT1, NOS2, CTNNA3, GSTP1, NFKBIA, ITGA3, BDKRB2, CDKN1A, CDKN2A, EDN1, HDAC2
 KEGG 58 / 533 4.1× 1.44e-20 1.18e-17 ✓ sig.
Lipid and atherosclerosis
ATF6, DDIT3, HSPA5, IL1B, NLRP3, TNF, NFKBIA, CYP2A6, CXCL1, CXCL2, CYBA, CYP1A1
 KEGG 36 / 216 6.3× 5.60e-19 3.57e-16 ✓ sig.
Fluid shear stress and atherosclerosis
GSTM1, GSTT1, IL1B, TNF, GSTP1, TXN, CYBA, EDN1, HMOX1, ICAM1, MMP9, NOS3
 KEGG 27 / 141 7.2× 4.63e-16 1.75e-13 ✓ sig.
Inflammatory bowel disease
IL1B, TNF, HLA-DPB1, IL12B, IL13, IL6, NOD2, TGFB1, TLR4, TLR5, IL18, TLR2
 KEGG 19 / 66 10.8× 3.99e-15 1.23e-12 ✓ sig.
Rheumatoid arthritis
IL1B, TNF, FLT1, CD86, CTLA4, CXCL1, CXCL2, HLA-DPB1, ICAM1, IL6, TGFB1, TLR4
 KEGG 22 / 95 8.7× 3.98e-15 1.23e-12 ✓ sig.
Cytokine-cytokine receptor interaction
IL1B, TNF, IL1RN, CCL1, CXCL1, CXCL2, IL12B, IL13, IL13RA1, IL27, IL6, LEP
 KEGG 36 / 298 4.5× 2.10e-14 5.62e-12 ✓ sig.
IL-17 signaling pathway
IL1B, TNF, NFKBIA, CXCL1, CXCL2, IL13, IL6, MMP9, PTGS2, CEBPB, CSF3, MMP1
 KEGG 20 / 94 8.0× 4.08e-13 8.41e-11 ✓ sig.
Legionellosis
IL1B, TNF, NFKBIA, CXCL1, CXCL2, HSPA1A, HSPA1B, HSPA1L, IL12B, IL6, TLR4, CD14
 KEGG 16 / 56 10.7× 7.06e-13 1.41e-10 ✓ sig.
Chagas disease
IL1B, NOS2, TNF, NFKBIA, ACE, BDKRB2, IL12B, IL6, TGFB1, TLR4, FAS, TLR9
 KEGG 20 / 103 7.3× 2.51e-12 4.34e-10 ✓ sig.
Amoebiasis
ARG1, IL1B, NOS2, PRDX1, TNF, CXCL1, CXCL2, IL12B, IL6, TGFB1, TLR4, CD14
 KEGG 19 / 103 6.9× 2.32e-11 3.25e-9 ✓ sig.
PI3K-Akt signaling pathway
SPP1, FLT1, MAGI2, ITGA3, CDKN1A, FOXO3, IL6, NOS3, TLR4, TP53, PIK3CG, TSC2
 KEGG 35 / 361 3.6× 3.10e-11 4.20e-9 ✓ sig.
HIF-1 signaling pathway
NOS2, FLT1, CDKN1A, EDN1, HIF1A, HMOX1, IL6, NOS3, TLR4, IGF1R, INSR, LDHC
 KEGG 19 / 110 6.5× 7.70e-11 9.29e-9 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
IL1B, TNF, EDN1, ICAM1, IL6, NOS3, TGFB1, AGER, VEGFA, IL1A, SERPINE1, CXCL8
 KEGG 18 / 101 6.7× 1.43e-10 1.60e-8 ✓ 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 ⇵
inflammatory response
IL1B, NLRP3, NOS2, TNF, IL1RN, NFKBIA, BDKRB2, CCL1, CRP, CXCL1, CXCL2, CYBA
 GO:0006954 53 / 467 6.6× 2.35e-28 1.19e-24 ✓ sig.
response to hypoxia
NOS2, TNF, ABAT, POSTN, CHRNA4, CHRNA7, CYBA, CYP1A1, EDN1, HIF1A, LEP, MMP14
 GO:0001666 30 / 176 10.0× 1.77e-21 3.59e-18 ✓ sig.
positive regulation of gene expression
IL1B, TNF, VDR, ITGA3, CDKN2A, CRP, HIF1A, HSPA1A, HSPA1B, IL13, IL6, NOS3
 GO:0010628 46 / 504 5.3× 1.08e-20 1.93e-17 ✓ sig.
positive regulation of cell migration
HSPA5, IL1B, FLT1, CCL1, EDN1, F2RL1, MMP14, TGFB1, AGER, CEACAM6, IGF1R, INSR
 GO:0030335 36 / 292 7.2× 1.19e-20 2.11e-17 ✓ sig.
immune response
IL1B, TNF, IL1RN, CCL1, CD86, CD8A, CRHR1, CTLA4, CXCL1, CXCL2, DEFB1, HLA-DPB1
 GO:0006955 47 / 543 5.1× 3.52e-20 5.77e-17 ✓ sig.
positive regulation of interleukin-8 production
DDIT3, IL1B, NOS2, TNF, F2RL1, HSPA1A, HSPA1B, IL6, LEP, NOD2, TLR4, CD14
 GO:0032757 20 / 65 18.0× 3.67e-20 5.96e-17 ✓ sig.
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
IL1B, TNF, FLT1, TXN, F2RL1, LEP, TGFB1, ENG, PIK3CG, ADRA2B, CAT, CSF3
 GO:0051897 31 / 217 8.3× 8.18e-20 1.27e-16 ✓ sig.
positive regulation of cell population proliferation
IL1B, FLT1, HTR1A, NANOGP8, CD86, CDKN1A, CHRNA7, EDN1, HDAC2, HTR2A, IL6, KLF5
 GO:0008284 46 / 532 5.0× 9.60e-20 1.47e-16 ✓ sig.
positive regulation of inflammatory response
IL1B, NLRP3, TNF, NFKBIA, ABCC1, CCL1, HTR2A, IL12B, TGFB1, TLR4, TRPV4, TLR9
 GO:0050729 24 / 122 11.5× 6.35e-19 8.63e-16 ✓ sig.
positive regulation of MAPK cascade
IL1B, PRDX2, TNF, FLT1, ADRB1, ADRB2, CHRNA7, EDN1, IL6, LEP, NOD2, TGFB1
 GO:0043410 29 / 224 7.6× 2.06e-17 2.27e-14 ✓ sig.
lung development
ITGA3, CYP1A2, MMP14, NOS3, ABCA3, CCN2, CRISPLD2, NKX2-1, PDGFRA, SPRY2, STRA6, VEGFA
 GO:0030324 21 / 108 11.4× 1.34e-16 1.28e-13 ✓ sig.
positive regulation of tumor necrosis factor production
CYBA, HDAC2, IL12B, IL6, LEP, MIF, NOD2, TGFB1, TLR4, TNFRSF8, AGER, CD14
 GO:0032760 21 / 113 10.9× 3.54e-16 3.12e-13 ✓ sig.
positive regulation of transcription by RNA polymerase II
ATF6, DDIT3, HSPA5, IL1B, NLRP3, TNF, GRHL2, KLF12, NFKBIA, VDR, ZNF728, ADRB2
 GO:0045944 63 / 1,208 3.0× 1.20e-15 9.70e-13 ✓ sig.
cellular response to lipopolysaccharide
IL1B, NLRP3, NOS2, TNF, CARD16, GSTP1, CD86, IL12B, IL6, MMP9, NOD2, TLR4
 GO:0071222 25 / 187 7.8× 1.68e-15 1.34e-12 ✓ sig.
positive regulation of ERK1 and ERK2 cascade
IL1B, TNF, CHRNA7, F2RL1, HTR2A, ICAM1, MIF, NOD2, TGFB1, TLR4, TRPV4, AGER
 GO:0070374 24 / 201 7.0× 8.13e-14 4.77e-11 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Chronic obstructive pulmonary disease Obstructive airway disease 0.382 39 3.73e-87 1.39e-85 ✓ sig.
Lung disease Obstructive airway disease 0.154 27 2.93e-37 6.62e-36 ✓ sig.
Obstructive airway disease Pulmonary fibrosis 0.150 27 1.27e-36 2.84e-35 ✓ sig.
Cystic fibrosis Lung disease 0.130 19 2.08e-27 3.83e-26 ✓ sig.
Lung disease Pulmonary fibrosis 0.117 22 2.29e-27 4.21e-26 ✓ sig.
Cystic fibrosis Obstructive airway disease 0.117 17 6.88e-24 1.14e-22 ✓ sig.
Chronic obstructive pulmonary disease Pulmonary fibrosis 0.088 12 4.19e-17 5.53e-16 ✓ sig.
Bronchopulmonary dysplasia Obstructive airway disease 0.082 11 3.49e-15 4.24e-14 ✓ sig.
Chronic obstructive pulmonary disease Cystic fibrosis 0.095 9 4.57e-14 5.26e-13 ✓ sig.
Asbestosis Cystic fibrosis 0.081 6 3.84e-11 3.72e-10 ✓ sig.
Bronchopulmonary dysplasia Lung disease 0.057 8 4.72e-10 4.20e-9 ✓ sig.
Asbestosis Bronchopulmonary dysplasia 0.068 4 1.44e-7 9.90e-7 ✓ sig.
Chronic obstructive pulmonary disease Susceptibility to respiratory infections associated with CD8alpha chain mutation 0.024 1 2.65e-3 3.41e-3 ✓ sig.
Cystic fibrosis Immunodeficiency 97 with autoinflammation 0.016 1 4.00e-3 4.91e-3 ✓ sig.
Obstructive airway disease Susceptibility to respiratory infections associated with CD8alpha chain mutation 0.010 1 6.39e-3 7.50e-3 ✓ sig.
Lung disease Lung disease, immunodeficiency, and chromosome breakage syndrome; 0.010 1 6.59e-3 7.69e-3 ✓ sig.