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 304

6 diseases · 8 shared-gene connections
6 Diseases
302 Unique genes
0.214 Avg. similarity score
Non-neoplastic peripheral nervous system 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 ⇵
Non-neoplastic peripheral nervous system disease 4 4 54
Peripheral nervous system disease 4 4 53
Nervous system disease 3 3 68
Charcot-Marie-Tooth disease axonal type 2CC 2 2 1
Peripheral neuropathy 2 2 192
Bell's palsy 1 1 56

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

Gene ⇵ Member diseases ⇵ Linked diseases
ABCB1 4 / 6 Nervous system disease, Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
ATF3 4 / 6 Nervous system disease, Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
CASP9 4 / 6 Nervous system disease, Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
CSF3 4 / 6 Nervous system disease, Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
CYP2C8 4 / 6 Nervous system disease, Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
DPYD 4 / 6 Nervous system disease, Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
GFAP 4 / 6 Nervous system disease, Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
NEFH 4 / 6 Charcot-Marie-Tooth disease axonal type 2CC, Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
NGF 4 / 6 Nervous system disease, Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
PNPLA6 4 / 6 Nervous system disease, Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
ABCA1 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
ABCC1 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
ALOX12 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
CACNA1B 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
CACNA1H 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
CDKN2A 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
CPT1C 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
CTLA4 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
DAPK1 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
DYNC1I1 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
ERCC1 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
ERCC3 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
ERCC4 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
GAN 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
GJB3 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
GJE1 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
GLI1 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
GSTP1 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
ICAM1 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
IGF1 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
IGF1R 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
IL6 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
JUN 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
MBL2 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
MKI67 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
MMP3 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
MYO5A 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
MYOT 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
NPY 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
PMP22 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
PPARD 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
PRKCE 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
PSMB1 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
RHOBTB2 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
SERPINB2 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
SLC12A6 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
SOD2 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
SOX8 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
TCF4 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
TNFRSF10A 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
UCHL1 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
XK 3 / 6 Non-neoplastic peripheral nervous system disease, Peripheral nervous system disease, Peripheral neuropathy
CDC5L 2 / 6 Bell's palsy, Nervous system disease
FARP1 2 / 6 Bell's palsy, Nervous system disease
GPC6 2 / 6 Nervous system disease, Peripheral neuropathy
GRIK2 2 / 6 Bell's palsy, Nervous system disease
GSTT1 2 / 6 Non-neoplastic peripheral nervous system disease, Peripheral neuropathy
ND1 2 / 6 Non-neoplastic peripheral nervous system disease, Peripheral neuropathy
SLC2A1 2 / 6 Bell's palsy, Nervous system disease
SUPT3H 2 / 6 Bell's palsy, Nervous system 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 ⇵
Antifolate resistance
ABCC2, ABCG2, DHFR, MTHFR, SHMT1, SLC19A1, TNF, TYMS, ABCC1, ALOX12, IL6
 KEGG 11 / 30 14.6× 7.57e-11 1.12e-8 ✓ sig.
Folate transport and metabolism
ABCC2, ABCG2, DHFR, MTHFR, SHMT1, SLC19A1, TYMS, ABCC1
 KEGG 8 / 31 10.3× 6.95e-7 3.55e-5 ✓ sig.
Lipid and atherosclerosis
CASP3, CASP9, CYP2C8, CYP2C9, FOS, NFATC2, TNF, TP53, ABCA1, ICAM1, IL6, JUN
 KEGG 17 / 216 3.1× 3.21e-5 8.84e-4 ✓ sig.
Caspase activation via Dependence Receptors in the absence of ligand
CASP3, CASP9, DCC
 Reactome 3 / 4 29.8× 6.18e-5 1.52e-3 ✓ sig.
Platinum drug resistance
MGST1, ABCC2, CASP3, CASP9, TP53, CDKN2A, ERCC1, GSTP1, GSTT1
 KEGG 9 / 75 4.8× 1.04e-4 2.33e-3 ✓ sig.
Viral protein interaction with cytokine and cytokine receptor
XCL2, TNF, IL6, TNFRSF10A, CCL17, CX3CL1, CXCL12, IL2RA, IL37, IL6R
 KEGG 10 / 100 4.0× 2.04e-4 3.97e-3 ✓ sig.
Pathways in cancer
MGST1, RARB, SLC2A1, CASP3, CASP9, FOS, HES5, NOTCH1, PTGS2, TP53, CDKN2A, DAPK1
 KEGG 27 / 533 2.0× 4.27e-4 7.04e-3 ✓ sig.
Pathways of neurodegeneration - multiple diseases
DNAH8, BDNF, CASP3, CASP9, NOS1, PTGS2, SLC6A3, SOD1, TNF, CACNA1B, IL6, ND1
 KEGG 25 / 480 2.1× 4.65e-4 7.53e-3 ✓ sig.
IL-17 signaling pathway
CASP3, CSF3, FOS, PTGS2, TNF, IL6, JUN, MMP3, CCL17
 KEGG 9 / 94 3.8× 5.83e-4 8.99e-3 ✓ sig.
Apoptosis
CASP3, CASP9, FOS, NGF, TNF, TP53, JUN, TNFRSF10A, AIFM1, LMNA, SPTAN1
 KEGG 11 / 137 3.2× 6.74e-4 1.01e-2 ✓ sig.
Metabolism of folate and pterines
DHFR, MTHFR, SHMT1, SLC19A1
 Reactome 4 / 17 9.4× 7.20e-4 1.06e-2 ✓ sig.
TNF signaling pathway
CASP3, FOS, PTGS2, TNF, ICAM1, IL6, JUN, MMP3, CX3CL1, MAP2K6
 KEGG 10 / 119 3.3× 8.26e-4 1.18e-2 ✓ sig.
ABC transporters
ABCB1, ABCC2, ABCG2, ABCA1, ABCC1, ABCA4
 KEGG 6 / 45 5.3× 8.58e-4 1.21e-2 ✓ sig.
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)
NFATC2, CTLA4, IL2RA
 Reactome 3 / 10 11.9× 1.66e-3 1.99e-2 ✓ sig.
Chemical carcinogenesis - DNA adducts
MGST1, CYP2C8, CYP2C9, PTGS2, GSTP1, GSTT1, NAT2
 KEGG 7 / 70 4.0× 1.83e-3 2.14e-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 ⇵
response to hypoxia
KCNMA1, NPPC, SLC2A1, ABCB1, CASP3, CASP9, CHRNA4, MTHFR, NOS1, PENK, TNF, ND1
 GO:0001666 16 / 176 5.6× 2.86e-8 4.22e-6 ✓ sig.
positive regulation of apoptotic process
KCNMA1, RARB, CASP3, CASP9, NEUROD1, NOD1, NOTCH1, SOD1, TNF, TP53, CDKN2A, CTLA4
 GO:0043065 20 / 326 3.8× 3.84e-7 3.75e-5 ✓ sig.
xenobiotic transport across blood-brain barrier
ABCB1, ABCC2, ABCG2, ABCC1
 GO:1990962 4 / 6 41.3× 9.78e-7 8.14e-5 ✓ sig.
cellular response to amyloid-beta
APOE, ADRB2, TNF, ABCC1, ICAM1, IGF1, IGF1R, EPHA4
 GO:1904646 8 / 53 9.3× 2.00e-6 1.44e-4 ✓ sig.
response to xenobiotic stimulus
NPPC, ABCB1, CASP3, FOS, MTHFR, NFATC2, SLC19A1, SLC6A3, SOD1, TNF, TP53, ABCA1
 GO:0009410 16 / 248 4.0× 3.00e-6 1.99e-4 ✓ sig.
replicative senescence
SERPINE1, TP53, CDKN2A, ERCC1, MME
 GO:0090399 5 / 16 19.3× 4.03e-6 2.53e-4 ✓ sig.
neurofilament bundle assembly
NEFH, NEFL, NEFM
 GO:0033693 3 / 3 61.9× 4.18e-6 2.60e-4 ✓ sig.
negative regulation of collagen biosynthetic process
NPPC, NOTCH1, IL6, PPARD, IL6R
 GO:0032966 5 / 17 18.2× 5.63e-6 3.30e-4 ✓ sig.
positive regulation of neuron apoptotic process
GRIK2, ASCL1, CASP3, CASP9, NOS1, TNF, TP53, AIFM1
 GO:0043525 8 / 65 7.6× 9.63e-6 5.06e-4 ✓ sig.
response to ethanol
NPPC, CSF3, FOS, PENK, SLC6A3, SOD1, TNF, GSTP1, ND4, NTRK3
 GO:0045471 10 / 110 5.6× 1.18e-5 5.93e-4 ✓ sig.
export across plasma membrane
ABCB1, ABCG2, ABCA1, ABCC1
 GO:0140115 4 / 10 24.8× 1.30e-5 6.42e-4 ✓ sig.
neurofilament cytoskeleton organization
SOD1, NEFH, ATP8A2, NEFL
 GO:0060052 4 / 10 24.8× 1.30e-5 6.42e-4 ✓ sig.
cellular response to hypoxia
FOS, NOTCH1, PTGS2, TP53, PPARD, PRKCE, AIFM1, ANGPT4, GNGT1, HIF3A, LMNA
 GO:0071456 11 / 139 4.9× 1.63e-5 7.68e-4 ✓ sig.
positive regulation of smooth muscle cell proliferation
HES5, TNF, IGF1, IL6, CDH13, CX3CL1, IL6R
 GO:0048661 7 / 52 8.3× 1.93e-5 8.72e-4 ✓ sig.
tetrahydrofolate metabolic process
DHFR, MTHFR, SHMT1, TYMS
 GO:0046653 4 / 11 22.5× 2.02e-5 9.04e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Non-neoplastic peripheral nervous system disease Peripheral nervous system disease 0.929 52 1.19e-145 2.22e-143 ✓ sig.
Non-neoplastic peripheral nervous system disease Peripheral neuropathy 0.280 54 4.24e-107 5.74e-105 ✓ sig.
Peripheral nervous system disease Peripheral neuropathy 0.268 52 2.70e-101 3.26e-99 ✓ sig.
Nervous system disease Peripheral nervous system disease 0.080 9 1.40e-12 1.77e-11 ✓ sig.
Nervous system disease Non-neoplastic peripheral nervous system disease 0.079 9 1.68e-12 2.07e-11 ✓ sig.
Bell's palsy Nervous system disease 0.042 5 4.64e-6 2.56e-5 ✓ sig.
Charcot-Marie-Tooth disease axonal type 2CC Peripheral nervous system disease 0.019 1 3.44e-3 4.44e-3 ✓ sig.
Charcot-Marie-Tooth disease axonal type 2CC Non-neoplastic peripheral nervous system disease 0.018 1 3.51e-3 4.51e-3 ✓ sig.