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 66

14 diseases · 18 shared-gene connections
14 Diseases
226 Unique genes
0.090 Avg. similarity score
Bradycardia Most-connected disease (6 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 ⇵
Bradycardia 6 6 26
Hypotension 6 6 67
Tremor 4 4 15
Amnesia 3 3 18
Catalepsy 3 3 16
Hyperkinesia 3 3 33
Cyp2d6 deficiency 2 2 1
Edema 2 2 49
Hyperalgesia 2 2 89
Catatonia 1 1 1
Neurogenic bladder 1 1 1
Retrograde amnesia 1 1 1
immunodeficiency 92 1 1 1
neurodevelopmental disorder with language impairment and behavioral abnormalities 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
POMC 5 / 14 Amnesia, Bradycardia, Catalepsy, Edema and 1 more
TAC1 5 / 14 Amnesia, Bradycardia, Edema, Hyperalgesia and 1 more
AGT 4 / 14 Bradycardia, Catalepsy, Hyperalgesia, Hypotension
CALCA 4 / 14 Catalepsy, Edema, Hyperalgesia, Hyperkinesia
DRD2 4 / 14 Bradycardia, Catalepsy, Hyperkinesia, Hypotension
GCG 4 / 14 Bradycardia, Catalepsy, Hyperkinesia, Hypotension
IL6 4 / 14 Amnesia, Edema, Hyperalgesia, Hypotension
KNG1 4 / 14 Bradycardia, Edema, Hyperalgesia, Hypotension
PDYN 4 / 14 Amnesia, Bradycardia, Hyperalgesia, Hypotension
TRH 4 / 14 Amnesia, Bradycardia, Catalepsy, Tremor
ADORA1 3 / 14 Bradycardia, Catalepsy, Hypotension
ADORA2A 3 / 14 Hyperkinesia, Hypotension, Tremor
AVP 3 / 14 Amnesia, Hyperalgesia, Hypotension
CNR1 3 / 14 Catalepsy, Hyperalgesia, Hypotension
CYP2D6 3 / 14 Bradycardia, Cyp2d6 deficiency, Tremor
DRD1 3 / 14 Catalepsy, Hyperkinesia, Hypotension
DRD3 3 / 14 Hyperalgesia, Hyperkinesia, Tremor
EDN1 3 / 14 Bradycardia, Hyperalgesia, Hypotension
IL1A 3 / 14 Amnesia, Hyperalgesia, Hypotension
IL2 3 / 14 Amnesia, Hyperkinesia, Hypotension
NGF 3 / 14 Amnesia, Hyperalgesia, Hyperkinesia
NTS 3 / 14 Bradycardia, Catalepsy, Hyperkinesia
OXT 3 / 14 Edema, Hyperkinesia, Hypotension
PRL 3 / 14 Bradycardia, Catalepsy, Hypotension
TNF 3 / 14 Edema, Hyperalgesia, Hypotension
VIP 3 / 14 Edema, Hyperalgesia, Hypotension
BDKRB2 2 / 14 Hyperalgesia, Hypotension
CACNA1D 2 / 14 Bradycardia, Edema
CAT 2 / 14 Edema, Hypotension
CCK 2 / 14 Catalepsy, Hyperkinesia
CHRM2 2 / 14 Bradycardia, Neurogenic bladder
CHRM4 2 / 14 Catatonia, Tremor
CNR2 2 / 14 Catalepsy, Hyperalgesia
CRH 2 / 14 Bradycardia, Hypotension
CRHR1 2 / 14 Hyperalgesia, Hyperkinesia
CXCL8 2 / 14 Edema, Hyperalgesia
EDN2 2 / 14 Bradycardia, Hypotension
EDN3 2 / 14 Bradycardia, Hypotension
FOS 2 / 14 Hyperalgesia, Hyperkinesia
GRIA1 2 / 14 Hyperkinesia, Hypotension
GRIA2 2 / 14 Hyperkinesia, neurodevelopmental disorder with language impairment and behavioral abnormalities
GRIN2B 2 / 14 Hyperalgesia, Hypotension
HTR1A 2 / 14 Bradycardia, Tremor
HTR2A 2 / 14 Hyperalgesia, Hyperkinesia
IL1B 2 / 14 Hyperalgesia, Hypotension
INS 2 / 14 Edema, Hypotension
NISCH 2 / 14 Bradycardia, Hypotension
PNOC 2 / 14 Hyperalgesia, Hypotension
PREP 2 / 14 Amnesia, Retrograde amnesia
PTGS2 2 / 14 Edema, Hyperalgesia
PTHLH 2 / 14 Edema, Hyperalgesia
REL 2 / 14 immunodeficiency 92, Tremor
SLC9A3 2 / 14 Edema, Hypotension
TACR1 2 / 14 Bradycardia, Hyperalgesia
TH 2 / 14 Catalepsy, Hyperkinesia
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 ⇵
Neuroactive ligand-receptor interaction
AVP, GRP, HRH3, PDYN, POMC, TAC1, TRH, ADORA1, AGT, CHRM2, CRH, DRD2
 KEGG 65 / 370 9.3× 1.28e-45 1.41e-41 ✓ sig.
cAMP signaling pathway
GNAI1, GNAI3, POMC, ADORA1, CACNA1D, CHRM2, CRH, DRD2, EDN1, EDN2, EDN3, GCG
 KEGG 42 / 226 9.9× 3.45e-30 1.03e-26 ✓ sig.
Hormone signaling
AVP, GNAI1, GNAI3, PDYN, POMC, TRH, AGT, CRH, DRD2, GCG, GNAI2, GNRH1
 KEGG 41 / 219 9.9× 1.32e-29 3.75e-26 ✓ sig.
Peptide ligand-binding receptors
GRP, PDYN, POMC, TRH, AGT, EDN1, EDN2, EDN3, KNG1, NTS, UTS2, CCK
 Reactome 28 / 106 14.0× 8.29e-25 1.48e-21 ✓ sig.
G alpha (q) signalling events
APP, AVP, GRP, TAC1, TRH, AGT, EDN1, EDN2, EDN3, GCG, GNRH1, KNG1
 Reactome 28 / 172 8.7× 1.08e-18 7.29e-16 ✓ sig.
Serotonergic synapse
APP, GNAI1, GNAI3, CACNA1D, CYP2D6, GNAI2, HTR1A, CASP3, KCNN2, PTGS2, ALOX12, ALOX5
 KEGG 23 / 115 10.6× 1.33e-17 7.07e-15 ✓ sig.
Chagas disease
GNAI1, GNAI3, IL2, IL6, GNAI2, KNG1, CASP8, CXCL8, TNF, BDKRB2, CCL2, FOS
 KEGG 22 / 103 11.4× 1.56e-17 8.21e-15 ✓ sig.
Calcium signaling pathway
NGF, CACNA1D, CHRM2, TACR1, DRD1, BDKRB1, BDKRB2, CACNA1H, CAMK2A, CCKBR, GDNF, GRIN1
 KEGG 31 / 254 6.5× 7.03e-17 3.25e-14 ✓ sig.
Inflammatory mediator regulation of TRP channels
NGF, KNG1, MAP2K6, ALOX12, BDKRB1, BDKRB2, CAMK2A, HTR2A, IGF1, IL1B, MAPK8, MAPK9
 KEGG 21 / 99 11.3× 1.01e-16 4.56e-14 ✓ sig.
G alpha (i) signalling events
APP, GNAI1, GNAI3, HRH3, PDYN, POMC, ADORA1, AGT, CHRM2, GNAI2, HTR1A, KNG1
 Reactome 30 / 249 6.4× 3.32e-16 1.39e-13 ✓ sig.
Circadian entrainment
GNAI1, GNAI3, CACNA1D, GNAI2, CACNA1H, CAMK2A, FOS, GRIN1, GRIN2B, MAPK1, MAPK3, NOS1
 KEGG 19 / 97 10.4× 1.47e-14 4.43e-12 ✓ sig.
Dopaminergic synapse
GNAI1, GNAI3, CACNA1D, DRD2, GNAI2, DRD1, PPP1R1B, TH, DRD3, CAMK2A, COMT, FOS
 KEGG 21 / 132 8.5× 4.53e-14 1.21e-11 ✓ sig.
Cocaine addiction
GNAI1, GNAI3, PDYN, DRD2, GNAI2, DRD1, PPP1R1B, TH, GRIN1, GRIN2B, GRIA2, SLC6A3
 KEGG 14 / 49 15.2× 1.76e-13 4.27e-11 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
IL1A, IL6, AGT, EDN1, CASP3, CXCL8, TNF, AGER, CCL2, IL1B, MAPK1, MAPK3
 KEGG 18 / 101 9.5× 4.17e-13 9.59e-11 ✓ sig.
Vascular smooth muscle contraction
AVP, AGT, CACNA1D, EDN1, EDN2, EDN3, CALCA, ADM, MAPK1, MAPK3, PRKCE, PRKCG
 KEGG 20 / 134 7.9× 6.48e-13 1.47e-10 ✓ 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 ⇵
signal transduction
AVP, CSF2, GNAI1, GNAI3, GRP, HRH3, NGF, POMC, TRH, ADORA1, CHRM2, CRH
 GO:0007165 81 / 2,125 3.2× 2.89e-22 6.35e-19 ✓ sig.
chemical synaptic transmission
APP, HRH3, PDYN, TAC1, CHRM2, CRH, HTR1A, UTS2, CHRM4, CARTPT, GRIN1, GRIN2B
 GO:0007268 30 / 236 10.5× 4.19e-22 9.04e-19 ✓ sig.
G protein-coupled receptor signaling pathway
APOE, APP, GNAI1, GNAI3, HRH3, IL2, ADORA1, AGT, CHRM2, DRD2, EDN1, GCG
 GO:0007186 53 / 1,031 4.3× 1.06e-19 1.64e-16 ✓ sig.
adenylate cyclase-activating G protein-coupled receptor signaling pathway
APP, AVP, GNAI1, GCG, GNAI2, HTR1A, CALCA, CNR1, CNR2, DRD1, PTHLH, VIP
 GO:0007189 24 / 161 12.3× 1.60e-19 2.40e-16 ✓ sig.
response to xenobiotic stimulus
AVP, CRH, CYP1A1, DRD2, EDN1, DRD1, FYN, AHR, CASP3, CAT, TNF, DRD3
 GO:0009410 28 / 248 9.3× 2.80e-19 4.08e-16 ✓ sig.
vasodilation
APOE, ADORA1, KNG1, CALCA, DRD1, INS, TNF, BDKRB2, GPER1, NOS1, ADORA2A, ACE
 GO:0042311 16 / 50 26.5× 4.20e-19 5.99e-16 ✓ sig.
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
HRH3, CHRM2, HTR1A, CNR1, CNR2, DRD1, CHRM4, CCL2, HTR2A, MC1R, OPRM1, HTR2C
 GO:0007187 16 / 54 24.5× 1.72e-18 2.23e-15 ✓ sig.
response to ethanol
AVP, IL2, CRH, DRD2, GNRH1, TACR1, FYN, TH, CASP8, CAT, TNF, DRD3
 GO:0045471 20 / 110 15.0× 3.23e-18 4.01e-15 ✓ sig.
response to hypoxia
ADORA1, CYP1A1, DRD2, EDN1, TH, CASP3, CASP9, CAT, TNF, AGER, COMT, ITGA2
 GO:0001666 23 / 176 10.8× 1.93e-17 2.14e-14 ✓ sig.
positive regulation of MAPK cascade
APP, IL6, ADORA1, EDN1, EDN3, DRD1, IL11, INS, MAP2K6, TNF, CARTPT, GPER1
 GO:0043410 25 / 224 9.2× 3.40e-17 3.57e-14 ✓ sig.
sensory perception of pain
NGF, TAC1, AQP1, CCL2, HOXD1, MAPK3, MC1R, MECP2, OPRM1, PNOC, PROK2, SCN11A
 GO:0019233 14 / 44 26.3× 7.97e-17 7.81e-14 ✓ sig.
regulation of blood pressure
POMC, TAC1, AGT, EDN1, TACR1, UTS2, CALCA, PTGS2, COMT, PTGS1, NPY, ACE
 GO:0008217 17 / 83 16.9× 1.39e-16 1.28e-13 ✓ sig.
negative regulation of blood pressure
ADORA1, DRD2, CALCA, OXT, DRD3, BDKRB1, NOS1, NOS2, NPY, APLN, NPPA, UCN
 GO:0045776 12 / 28 35.4× 1.87e-16 1.67e-13 ✓ sig.
blood vessel diameter maintenance
AVP, AGT, EDN1, EDN2, EDN3, KNG1, NTS, UTS2, NPPC, ACE, NPPA, NPPB
 GO:0097746 13 / 37 29.1× 2.31e-16 2.04e-13 ✓ sig.
neuropeptide signaling pathway
GNAI1, GRP, PDYN, POMC, TAC1, NTS, CARTPT, CCKBR, GAL, OPRM1, PNOC, PROK2
 GO:0007218 18 / 111 13.4× 1.37e-15 1.03e-12 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Bradycardia Hypotension 0.175 14 1.89e-27 5.53e-26 ✓ sig.
Hyperalgesia Hypotension 0.106 15 2.12e-20 4.34e-19 ✓ sig.
Bradycardia Catalepsy 0.229 8 2.55e-19 4.93e-18 ✓ sig.
Catalepsy Hypotension 0.105 8 1.04e-15 1.65e-14 ✓ sig.
Catalepsy Hyperkinesia 0.163 7 1.19e-15 1.87e-14 ✓ sig.
Edema Hypotension 0.093 10 8.68e-15 1.29e-13 ✓ sig.
Amnesia Hypotension 0.089 7 6.55e-13 8.50e-12 ✓ sig.
Edema Hyperalgesia 0.069 9 8.09e-12 9.48e-11 ✓ sig.
Hyperkinesia Hypotension 0.074 7 8.36e-11 8.89e-10 ✓ sig.
Amnesia Bradycardia 0.098 4 1.92e-8 1.59e-7 ✓ sig.
Bradycardia Tremor 0.077 3 1.92e-6 1.13e-5 ✓ sig.
Cyp2d6 deficiency Tremor 0.063 1 9.74e-4 1.64e-3 ✓ sig.
Catatonia Tremor 0.063 1 9.74e-4 1.64e-3 ✓ sig.
immunodeficiency 92 Tremor 0.063 1 9.74e-4 1.64e-3 ✓ sig.
Amnesia Retrograde amnesia 0.053 1 1.17e-3 1.88e-3 ✓ sig.
Bradycardia Cyp2d6 deficiency 0.037 1 1.69e-3 2.51e-3 ✓ sig.
Bradycardia Neurogenic bladder 0.037 1 1.69e-3 2.51e-3 ✓ sig.
Hyperkinesia neurodevelopmental disorder with language impairment and behavioral abnormalities 0.029 1 2.14e-3 3.03e-3 ✓ sig.