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 537

5 diseases · 8 shared-gene connections
5 Diseases
74 Unique genes
0.133 Avg. similarity score
Cognition disorder 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 ⇵
Cognition disorder 4 4 54
Delirium, dementia, and cognitive disorders 4 4 56
Bile acid malabsorption 3 3 3
Diabetes complications 3 3 12
Parkinson disease 6, early onset 2 2 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
SLC10A2 4 / 5 Bile acid malabsorption, Cognition disorder, Delirium, dementia, and cognitive disorders, Diabetes complications
SLC51B 4 / 5 Bile acid malabsorption, Cognition disorder, Delirium, dementia, and cognitive disorders, Diabetes complications
ABCC4 3 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders, Diabetes complications
NR0B2 3 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders, Diabetes complications
PINK1 3 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders, Parkinson disease 6, early onset
SLC51A 3 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders, Diabetes complications
AFF4 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
AGT 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
APOE 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
APP 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
BCHE 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
CAPN2 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
CDK5R1 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
CNR1 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
COMT 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
CRH 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
DRD2 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
DRD3 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
EIF2S1 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
EPO 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
FGF14 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
FMR1 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
FOSB 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
GSK3B 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
HTR2A 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
IGF2 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
LAMB2 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
LEPR 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
MAOA 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
MAPT 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
MET 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
OTC 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
OXTR 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
PHLDA1 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
PSEN1 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
PTGS2 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
SETD7 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
SLC1A1 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
SLC4A10 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
SLC6A4 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
SMAD4 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
TSC1 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
VIP 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
WDR48 2 / 5 Cognition disorder, Delirium, dementia, and cognitive disorders
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 ⇵
Hormone signaling
AGT, CRH, DRD2, DRD3, EPO, IGF2, LEPR, OXTR, SMAD4, VIP, INS
 KEGG 11 / 219 8.2× 8.80e-8 4.99e-6 ✓ sig.
Serotonergic synapse
APP, HTR2A, MAOA, PTGS2, SLC6A4, CACNA1C, CYP2D6
 KEGG 7 / 115 9.9× 6.51e-6 2.04e-4 ✓ sig.
PI3K-Akt signaling pathway
EPO, GSK3B, IGF2, LAMB2, MET, TSC1, VEGFA, BDNF, CSF3, FGF2, INS
 KEGG 11 / 361 4.9× 1.19e-5 3.36e-4 ✓ sig.
Cocaine addiction
CDK5R1, DRD2, FOSB, MAOA, BDNF
 KEGG 5 / 49 16.6× 1.20e-5 3.38e-4 ✓ sig.
Alzheimer disease
APOE, APP, CAPN2, CDK5R1, EIF2S1, GSK3B, MAPT, PSEN1, PTGS2, CACNA1C, INS
 KEGG 11 / 388 4.6× 2.33e-5 5.91e-4 ✓ sig.
Regulation of gene expression by Hypoxia-inducible Factor
EPO, HIF1A, VEGFA
 Reactome 3 / 11 44.3× 3.58e-5 8.36e-4 ✓ sig.
Enzymatic degradation of Dopamine by monoamine oxidase
COMT, MAOA
 Reactome 2 / 2 162× 3.75e-5 8.67e-4 ✓ sig.
Metabolism of serotonin
MAOA, ALDH2
 Reactome 2 / 2 162× 3.75e-5 8.67e-4 ✓ sig.
Pathways in cancer
AGT, EPO, GSK3B, IGF2, LAMB2, MET, PTGS2, SMAD4, HIF1A, VEGFA, FGF2, PPARG
 KEGG 12 / 533 3.7× 9.14e-5 1.77e-3 ✓ sig.
Enzymatic degradation of dopamine by COMT
COMT, MAOA
 Reactome 2 / 3 108× 1.12e-4 2.08e-3 ✓ sig.
Metallothioneins bind metals
MT1A, MT2A
 Reactome 2 / 3 108× 1.12e-4 2.08e-3 ✓ sig.
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models
APP, CAPN2, CDK5R1
 Reactome 3 / 16 30.4× 1.19e-4 2.17e-3 ✓ sig.
Dopaminergic synapse
COMT, DRD2, DRD3, GSK3B, MAOA, CACNA1C
 KEGG 6 / 132 7.4× 1.58e-4 2.73e-3 ✓ sig.
Pathways of neurodegeneration - multiple diseases
APP, CAPN2, CDK5R1, EIF2S1, GSK3B, MAPT, PINK1, PSEN1, PTGS2, CACNA1C, BDNF
 KEGG 11 / 480 3.7× 1.59e-4 2.73e-3 ✓ sig.
Bile secretion
SLC10A2, SLC51B, ABCC4, NR0B2, SLC51A
 KEGG 5 / 90 9.0× 2.27e-4 3.62e-3 ✓ 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 ⇵
negative regulation of gene expression
AGT, APOE, APP, CRH, GSK3B, MAPT, NR0B2, PINK1, PSEN1, PICALM, HIF1A, VEGFA
 GO:0010629 15 / 339 11.2× 3.86e-12 1.62e-9 ✓ sig.
learning or memory
APP, COMT, CRH, DRD3, MAPT, PSEN1, SLC1A1, PICALM
 GO:0007611 8 / 72 28.1× 4.01e-10 1.06e-7 ✓ sig.
positive regulation of amyloid fibril formation
APOE, APP, PSEN1, CLU
 GO:1905908 4 / 5 202× 1.13e-9 2.57e-7 ✓ sig.
memory
APP, COMT, HTR2A, MAPT, PSEN1, SLC1A1, SLC6A4, TAFA2
 GO:0007613 8 / 87 23.2× 1.87e-9 4.00e-7 ✓ sig.
behavioral response to cocaine
DRD2, DRD3, FOSB, HTR2A, SLC6A4
 GO:0048148 5 / 17 74.3× 5.06e-9 9.70e-7 ✓ sig.
response to ethanol
CRH, DRD2, DRD3, FOSB, NR0B2, SETD7, CSF3, FGF2
 GO:0045471 8 / 110 18.4× 1.22e-8 2.09e-6 ✓ sig.
synapse organization
APP, LAMB2, MAPT, PSEN1, SLC1A1, TSC1, APBB2
 GO:0050808 7 / 72 24.6× 1.37e-8 2.32e-6 ✓ sig.
positive regulation of glycolytic process
APP, HTR2A, PSEN1, HIF1A, INS
 GO:0045821 5 / 24 52.6× 3.40e-8 5.12e-6 ✓ sig.
response to xenobiotic stimulus
BCHE, COMT, CRH, DRD2, DRD3, FOSB, HTR2A, OTC, SLC1A1, SLC6A4
 GO:0009410 10 / 248 10.2× 4.82e-8 6.86e-6 ✓ sig.
regulation of amyloid-beta clearance
APOE, APP, CLU
 GO:1900221 3 / 3 253× 5.96e-8 8.23e-6 ✓ sig.
visual learning
APP, COMT, DRD2, DRD3, TAFA2, HIF1A
 GO:0008542 6 / 54 28.1× 6.97e-8 9.41e-6 ✓ sig.
positive regulation of gene expression
APP, CRH, GSK3B, NR0B2, PSEN1, SLC6A4, SMAD4, CLU, HIF1A, VEGFA, FGF2, INS
 GO:0010628 13 / 504 6.5× 7.99e-8 1.05e-5 ✓ sig.
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
AGT, APP, GSK3B, IGF2, PINK1, VEGFA, CSF3, FGF2, INS
 GO:0051897 9 / 217 10.5× 1.87e-7 2.13e-5 ✓ sig.
response to morphine
DRD2, DRD3, FOSB, SLC1A1
 GO:0043278 4 / 14 72.2× 2.20e-7 2.45e-5 ✓ sig.
response to cocaine
CRH, DRD2, DRD3, FOSB, HTR2A
 GO:0042220 5 / 35 36.1× 2.51e-7 2.74e-5 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Cognition disorder Delirium, dementia, and cognitive disorders 0.657 44 1.64e-108 7.39e-107 ✓ sig.
Cognition disorder Diabetes complications 0.081 5 3.31e-10 2.97e-9 ✓ sig.
Delirium, dementia, and cognitive disorders Diabetes complications 0.078 5 4.00e-10 3.57e-9 ✓ sig.
Bile acid malabsorption Diabetes complications 0.143 2 1.65e-6 9.79e-6 ✓ sig.
Bile acid malabsorption Cognition disorder 0.036 2 3.57e-5 1.84e-4 ✓ sig.
Bile acid malabsorption Delirium, dementia, and cognitive disorders 0.034 2 3.84e-5 1.97e-4 ✓ sig.
Cognition disorder Parkinson disease 6, early onset 0.018 1 3.49e-3 4.34e-3 ✓ sig.
Delirium, dementia, and cognitive disorders Parkinson disease 6, early onset 0.018 1 3.62e-3 4.49e-3 ✓ sig.