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 29

18 diseases · 24 shared-gene connections
18 Diseases
177 Unique genes
0.126 Avg. similarity score
Avascular necrosis of bone Most-connected disease (7 links)
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Disease Searched: hereditary fructose intolerance 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 ⇵
Avascular necrosis of bone 7 7 14
Osteonecrosis of medial femoral condyle 7 7 14
Hypoxia 6 6 33
Angle closure glaucoma 4 4 14
Hypospadias 3 3 42
Primary angle closure glaucoma 3 3 16
Pulmonary edema 3 3 16
Raynaud disease 3 3 13
Osteonecrosis of the femoral head 2 2 52
Senile cataract 2 2 13
Chromosome 5q deletion syndrome 1 1 1
Rhizomelic limb shortening with dysmorphic features 1 1 1
Sarcosinemia 1 1 1
Wernicke encephalopathy 1 1 1
congenital muscular dystrophy with intellectual disability and severe epilepsy 1 1 1
hereditary fructose intolerance 1 1 1
primary angle-closure glaucoma 1 1 0
schuurs-hoeijmakers syndrome 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
GSTM1 7 / 18 Angle closure glaucoma, Avascular necrosis of bone, Hypospadias, Osteonecrosis of medial femoral condyle and 3 more
NOS3 7 / 18 Angle closure glaucoma, Avascular necrosis of bone, Hypoxia, Osteonecrosis of medial femoral condyle and 3 more
CAT 6 / 18 Angle closure glaucoma, Avascular necrosis of bone, Osteonecrosis of medial femoral condyle, Osteonecrosis of the femoral head and 2 more
GSTT1 6 / 18 Avascular necrosis of bone, Hypospadias, Osteonecrosis of medial femoral condyle, Osteonecrosis of the femoral head and 2 more
PLAT 4 / 18 Avascular necrosis of bone, Hypoxia, Osteonecrosis of medial femoral condyle, Osteonecrosis of the femoral head
TFPI 4 / 18 Avascular necrosis of bone, Hypoxia, Osteonecrosis of medial femoral condyle, Osteonecrosis of the femoral head
ABCB1 3 / 18 Avascular necrosis of bone, Osteonecrosis of medial femoral condyle, Osteonecrosis of the femoral head
ANXA2 3 / 18 Avascular necrosis of bone, Osteonecrosis of medial femoral condyle, Osteonecrosis of the femoral head
COL2A1 3 / 18 Avascular necrosis of bone, Osteonecrosis of medial femoral condyle, Osteonecrosis of the femoral head
F2 3 / 18 Avascular necrosis of bone, Osteonecrosis of medial femoral condyle, Osteonecrosis of the femoral head
F5 3 / 18 Avascular necrosis of bone, Osteonecrosis of medial femoral condyle, Osteonecrosis of the femoral head
IL23R 3 / 18 Avascular necrosis of bone, Osteonecrosis of medial femoral condyle, Osteonecrosis of the femoral head
MMP2 3 / 18 Avascular necrosis of bone, Osteonecrosis of medial femoral condyle, Osteonecrosis of the femoral head
TRPV4 3 / 18 Avascular necrosis of bone, Osteonecrosis of medial femoral condyle, Osteonecrosis of the femoral head
ADK 2 / 18 Hypospadias, Hypoxia
ALDOB 2 / 18 hereditary fructose intolerance, Hypoxia
COL11A1 2 / 18 Angle closure glaucoma, Primary angle closure glaucoma
DPM2 2 / 18 congenital muscular dystrophy with intellectual disability and severe epilepsy, Primary angle closure glaucoma
EPDR1 2 / 18 Angle closure glaucoma, Primary angle closure glaucoma
FERMT2 2 / 18 Angle closure glaucoma, Primary angle closure glaucoma
GLIS3 2 / 18 Angle closure glaucoma, Primary angle closure glaucoma
PACS1 2 / 18 Hypospadias, schuurs-hoeijmakers syndrome
PKDCC 2 / 18 Hypospadias, Rhizomelic limb shortening with dysmorphic features
PLEKHA7 2 / 18 Angle closure glaucoma, Primary angle closure glaucoma
RPS14 2 / 18 Chromosome 5q deletion syndrome, Hypoxia
SARDH 2 / 18 Hypoxia, Sarcosinemia
TKT 2 / 18 Hypoxia, Wernicke encephalopathy
ZFHX3 2 / 18 Hypospadias, Raynaud 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 ⇵
Fluid shear stress and atherosclerosis
GSTM1, MMP9, NOS3, GSTT1, MMP2, PLAT, TRPV4, PIK3CA, ACTB, ACVR1, MAPK14, TNF
 KEGG 14 / 141 6.7× 1.93e-8 1.47e-6 ✓ sig.
Estrogen signaling pathway
MMP9, NOS3, MMP2, ESR2, PIK3CA, SP1, ATF4, GNAS, POMC, OPRM1, TGFA, HSPA1B
 KEGG 12 / 139 5.9× 9.49e-7 4.48e-5 ✓ sig.
Opioid Signalling
PDYN, POMC, OPRM1
 Reactome 3 / 3 67.9× 3.15e-6 1.25e-4 ✓ sig.
Lipid and atherosclerosis
MMP9, NOS3, CYP1A1, PIK3CA, APOA1, ATF4, SOD2, ABCG1, PPARG, MAPK14, NLRP3, TNF
 KEGG 14 / 216 4.4× 3.68e-6 1.43e-4 ✓ sig.
Prostate cancer
MMP9, PLAT, AR, PIK3CA, SRD5A2, ATF4, TGFA, GSTP1, TCF7L2
 KEGG 9 / 98 6.2× 1.37e-5 4.23e-4 ✓ sig.
Pathways in cancer
GSTM1, HGF, MMP9, F2, GSTT1, IL23R, MMP2, AR, ESR2, HHIP, PIK3CA, SP1
 KEGG 21 / 533 2.7× 3.75e-5 9.83e-4 ✓ sig.
Hepatocellular carcinoma
GSTM1, HGF, GSTT1, PIK3CA, WNT11, WNT8A, ACTB, TXNRD2, TGFA, GSTP1, TCF7L2
 KEGG 11 / 170 4.4× 4.24e-5 1.09e-3 ✓ sig.
Hormone signaling
ESR2, PIK3CA, GNAS, NOS1, NPPA, PDYN, POMC, OPRM1, ACVR1, ADIPOQ, GHRH, ADRA2A
 KEGG 12 / 219 3.7× 9.60e-5 2.12e-3 ✓ sig.
Interleukin-4 and Interleukin-13 signaling
HGF, MMP9, IL23R, MMP2, POMC, OPRM1, IL17A, TNF
 Reactome 8 / 108 5.0× 1.91e-4 3.67e-3 ✓ sig.
Extra-nuclear estrogen signaling
MMP9, NOS3, MMP2, ESR2, PIK3CA, TGFA
 Reactome 6 / 58 7.0× 2.02e-4 3.83e-3 ✓ sig.
HDL remodeling
APOE, APOA1, ABCG1
 Reactome 3 / 10 20.4× 3.50e-4 5.95e-3 ✓ sig.
Glutathione conjugation
GSTM1, GSTT1, ESD, GSTP1
 Reactome 4 / 24 11.3× 3.85e-4 6.43e-3 ✓ sig.
Androgen biosynthesis
HSD3B2, SRD5A2, POMC
 Reactome 3 / 11 18.5× 4.76e-4 7.59e-3 ✓ sig.
Endocrine resistance
MMP9, MMP2, ESR2, PIK3CA, SP1, GNAS, MAPK14
 KEGG 7 / 99 4.8× 6.39e-4 9.54e-3 ✓ sig.
Response of EIF2AK1 (HRI) to heme deficiency
ATF3, ATF4
 Reactome 2 / 3 45.2× 6.42e-4 9.57e-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 ⇵
response to hypoxia
CAT, MTHFR, ABCB1, MMP2, PLAT, TRPV4, CYP1A1, KCNMA1, CA9, EGR1, NOS1, NPPA
 GO:0001666 16 / 176 9.6× 1.14e-11 4.15e-9 ✓ sig.
positive regulation of transcription by RNA polymerase II
GLIS3, HGF, ANXA2, AR, ATF3, BMP7, ESR2, EYA1, GREM1, HOXA4, IRX6, KAT6B
 GO:0045944 37 / 1,208 3.2× 1.60e-10 4.50e-8 ✓ sig.
response to oxidative stress
APOE, CAT, MMP2, DGKK, MPO, SOD2, RIPK1, TXNRD2, ATM, ERCC2, OGG1, WRN
 GO:0006979 12 / 146 8.7× 1.47e-8 2.37e-6 ✓ sig.
vasodilation
APOE, NOS3, KCNMA1, NOS1, NPPA, SOD2, TNF, ADRA2A
 GO:0042311 8 / 50 16.9× 2.11e-8 3.24e-6 ✓ sig.
response to nutrient levels
ABCB1, SRD5A2, WNT11, ATF4, SOD2, PPARG, ADIPOQ, TNF, GSTP1
 GO:0031667 9 / 79 12.0× 5.83e-8 7.60e-6 ✓ sig.
response to hyperoxia
CAT, MMP2, CYP1A1, SOD2, TXNRD2
 GO:0055093 5 / 14 37.7× 1.35e-7 1.54e-5 ✓ sig.
response to activity
CAT, ANXA2, MMP2, PIK3CA, SOD2, ADIPOQ, TNF
 GO:0014823 7 / 52 14.2× 5.67e-7 5.19e-5 ✓ sig.
positive regulation of DNA-templated transcription
APOE, AR, BMP7, ESR2, EYA1, GREM1, IRX6, KAT6B, SP1, WNT11, ZFHX3, ACTB
 GO:0045893 23 / 778 3.1× 1.30e-6 1.03e-4 ✓ sig.
response to lipopolysaccharide
NOS3, ABCB1, IL23R, CYP1A1, MPO, NOS1, PCK2, SOD2, MAPK14, TNF
 GO:0032496 10 / 161 6.6× 3.19e-6 2.11e-4 ✓ sig.
response to L-ascorbic acid
CAT, SOD2, GSTP1
 GO:0033591 3 / 4 79.2× 3.32e-6 2.18e-4 ✓ sig.
positive regulation of cholesterol efflux
APOE, APOA1, ABCG1, PPARG, ADIPOQ
 GO:0010875 5 / 27 19.6× 4.91e-6 2.99e-4 ✓ sig.
positive regulation of gene expression
NOS3, TRPV4, AR, ATF3, BMP7, SP1, ATF4, EGR1, CUX2, PPARG, RIPK1, SFRP4
 GO:0010628 17 / 504 3.6× 6.34e-6 3.67e-4 ✓ sig.
osteoblast differentiation
CAT, BMP7, SND1, SP7, WNT11, ATP5F1B, ACVR1, MAPK14, ACVR2A
 GO:0001649 9 / 137 6.9× 6.34e-6 3.67e-4 ✓ sig.
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
COL2A1, EYA1, RIPK1, TNF, HSPA1B
 GO:2001240 5 / 37 14.3× 2.46e-5 1.05e-3 ✓ sig.
response to xenobiotic stimulus
CAT, MTHFR, ABCB1, MMP2, CYP1A1, SRD5A2, CA9, SOD2, COL18A1, ADIPOQ, TNF
 GO:0009410 11 / 248 4.7× 2.53e-5 1.08e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Avascular necrosis of bone Osteonecrosis of medial femoral condyle 0.933 14 2.08e-48 1.04e-46 ✓ sig.
Avascular necrosis of bone Osteonecrosis of the femoral head 0.264 14 3.68e-36 1.39e-34 ✓ sig.
Osteonecrosis of medial femoral condyle Osteonecrosis of the femoral head 0.264 14 3.68e-36 1.39e-34 ✓ sig.
Angle closure glaucoma Primary angle closure glaucoma 0.185 5 1.71e-12 1.99e-11 ✓ sig.
Avascular necrosis of bone Raynaud disease 0.120 3 1.70e-7 1.15e-6 ✓ sig.
Osteonecrosis of medial femoral condyle Senile cataract 0.120 3 1.70e-7 1.15e-6 ✓ sig.
Avascular necrosis of bone Senile cataract 0.120 3 1.70e-7 1.15e-6 ✓ sig.
Osteonecrosis of medial femoral condyle Raynaud disease 0.120 3 1.70e-7 1.15e-6 ✓ sig.
Angle closure glaucoma Avascular necrosis of bone 0.115 3 2.17e-7 1.43e-6 ✓ sig.
Angle closure glaucoma Osteonecrosis of medial femoral condyle 0.115 3 2.17e-7 1.43e-6 ✓ sig.
Avascular necrosis of bone Hypoxia 0.067 3 3.21e-6 1.73e-5 ✓ sig.
Hypoxia Osteonecrosis of medial femoral condyle 0.067 3 3.21e-6 1.73e-5 ✓ sig.
Hypospadias Raynaud disease 0.057 3 5.30e-6 2.74e-5 ✓ sig.
Angle closure glaucoma Pulmonary edema 0.069 2 9.15e-5 3.25e-4 ✓ sig.
Avascular necrosis of bone Pulmonary edema 0.069 2 9.15e-5 3.25e-4 ✓ sig.
Osteonecrosis of medial femoral condyle Pulmonary edema 0.069 2 9.15e-5 3.25e-4 ✓ sig.
Primary angle closure glaucoma primary angle-closure glaucoma 0.056 1 1.10e-3 1.83e-3 ✓ sig.
congenital muscular dystrophy with intellectual disability and severe epilepsy Primary angle closure glaucoma 0.056 1 1.10e-3 1.83e-3 ✓ sig.
hereditary fructose intolerance Hypoxia 0.029 1 2.14e-3 3.04e-3 ✓ sig.
Hypoxia Sarcosinemia 0.029 1 2.14e-3 3.04e-3 ✓ sig.
Chromosome 5q deletion syndrome Hypoxia 0.029 1 2.14e-3 3.04e-3 ✓ sig.
Hypoxia Wernicke encephalopathy 0.029 1 2.14e-3 3.04e-3 ✓ sig.
Hypospadias Rhizomelic limb shortening with dysmorphic features 0.023 1 2.73e-3 3.66e-3 ✓ sig.
Hypospadias schuurs-hoeijmakers syndrome 0.023 1 2.73e-3 3.66e-3 ✓ sig.