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 256

7 diseases · 9 shared-gene connections
7 Diseases
46 Unique genes
0.095 Avg. similarity score
Hemiparkinsonism Most-connected disease (4 links)
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Disease Searched: Parkinsonian-pyramidal 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 ⇵
Hemiparkinsonism 4 4 3
Secondary parkinson disease 4 4 15
Hereditary parkinson disease 3 3 28
Juvenile parkinsonism 2 2 3
Parkinsonian-pyramidal syndrome 2 2 2
Vesiculobullous skin disease 2 2 1
Thyroid hemiagenesis 1 1 2

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

Gene ⇵ Member diseases ⇵ Linked diseases
SNCA 4 / 7 Hemiparkinsonism, Hereditary parkinson disease, Parkinsonian-pyramidal syndrome, Secondary parkinson disease
PRKN 3 / 7 Hereditary parkinson disease, Secondary parkinson disease, Vesiculobullous skin disease
DNAJC6 2 / 7 Hemiparkinsonism, Juvenile parkinsonism
PODXL 2 / 7 Hereditary parkinson disease, Juvenile parkinsonism
VPS13C 2 / 7 Hemiparkinsonism, Thyroid hemiagenesis
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 ⇵
Parkinson disease
SNCA, LRRK2, MAPT, ND1, PARK7, PINK1, PRKN, SNCAIP, SLC18A2, PSMD3
 KEGG 10 / 268 9.7× 5.20e-8 3.90e-6 ✓ sig.
Pathways of neurodegeneration - multiple diseases
SNCA, LRRK2, MAPT, ATXN2, ATXN3, ND1, PARK7, PINK1, PRKN, SNCAIP, NOS2, PSMD3
 KEGG 12 / 480 6.5× 1.63e-7 1.07e-5 ✓ sig.
Josephin domain DUBs
ATXN3, PRKN
 Reactome 2 / 12 43.5× 9.24e-4 1.32e-2 ✓ sig.
Spinocerebellar ataxia
ATXN2, ATXN3, TBP, PSMD3
 KEGG 4 / 144 7.3× 2.19e-3 2.53e-2 ✓ sig.
Amyotrophic lateral sclerosis
ATXN2, ND1, PINK1, PRKN, NOS2, PSMD3
 KEGG 6 / 368 4.3× 2.64e-3 2.89e-2 ✓ sig.
Pink/Parkin Mediated Mitophagy
PINK1, PRKN
 Reactome 2 / 22 23.7× 3.16e-3 3.27e-2 ✓ sig.
Arginine biosynthesis
GLUD2, NOS2
 KEGG 2 / 23 22.7× 3.45e-3 3.49e-2 ✓ sig.
Amyloid fiber formation
SNCA, PRKN, SNCAIP
 Reactome 3 / 109 7.2× 8.32e-3 6.29e-2
Aggrephagy
PARK7, PRKN
 Reactome 2 / 40 13.1× 1.02e-2 7.18e-2
Inhibition of nitric oxide production
NOS2
 Reactome 1 / 3 87.0× 1.14e-2 7.70e-2
Nitric oxide stimulates guanylate cyclase
NOS2
 Reactome 1 / 3 87.0× 1.14e-2 7.70e-2
Mitochondrial transcription initiation
TFAM
 Reactome 1 / 3 87.0× 1.14e-2 7.70e-2
HHAT G278V abrogates palmitoylation of Hh-Np
SHH
 Reactome 1 / 4 65.3× 1.52e-2 9.14e-2
Neurotransmitter clearance
BCHE
 Reactome 1 / 4 65.3× 1.52e-2 9.14e-2
Arginine and proline metabolism
GAMT, NOS2
 KEGG 2 / 50 10.4× 1.56e-2 9.30e-2

Enriched GO Terms (Biological Process, a second line of biological evidence)

GO term ⇵ GO ID ⇵ Overlap genes ⇵ Fold enrichment ⇵ P-value ⇵ FDR q-value ⇵
adult locomotory behavior
SNCA, GIGYF2, NR4A2, PARK7, PRKN, GDNF
 GO:0008344 6 / 56 43.5× 4.69e-9 8.75e-7 ✓ sig.
negative regulation of neuron apoptotic process
SNCA, FGF20, NR4A2, PARK7, PINK1, PRKN, GDNF, FBXO7
 GO:0043524 8 / 160 20.3× 4.80e-9 8.90e-7 ✓ sig.
cellular response to oxidative stress
SNCA, LRRK2, NR4A2, PARK7, PINK1, PRKN, ATP13A2
 GO:0034599 7 / 111 25.6× 9.53e-9 1.63e-6 ✓ sig.
regulation of synaptic vesicle transport
LRRK2, PINK1, PRKN
 GO:1902803 3 / 3 406× 1.40e-8 2.28e-6 ✓ sig.
mitochondrion to lysosome vesicle-mediated transport
VPS35, PINK1, PRKN
 GO:0099074 3 / 3 406× 1.40e-8 2.28e-6 ✓ sig.
negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
PARK7, PINK1, PRKN, FBXO7
 GO:1903377 4 / 14 116× 3.16e-8 4.62e-6 ✓ sig.
dopamine metabolic process
SNCA, NR4A2, PRKN, SNCAIP
 GO:0042417 4 / 18 90.3× 9.59e-8 1.19e-5 ✓ sig.
negative regulation of mitochondrial fission
MAPT, PINK1, PRKN
 GO:0090258 3 / 5 244× 1.39e-7 1.63e-5 ✓ sig.
positive regulation of protein localization to cell periphery
SNCA, VPS35, EIF4G1
 GO:1904377 3 / 5 244× 1.39e-7 1.63e-5 ✓ sig.
regulation of mitochondrion organization
VPS35, PINK1, PRKN, ATP13A2
 GO:0010821 4 / 22 73.9× 2.28e-7 2.49e-5 ✓ sig.
regulation of locomotion
SNCA, LRRK2, FBXO7
 GO:0040012 3 / 6 203× 2.78e-7 2.94e-5 ✓ sig.
dopamine uptake involved in synaptic transmission
SNCA, PARK7, PRKN
 GO:0051583 3 / 6 203× 2.78e-7 2.94e-5 ✓ sig.
cellular response to manganese ion
LRRK2, PRKN, ATP13A2
 GO:0071287 3 / 7 174× 4.85e-7 4.68e-5 ✓ sig.
regulation of reactive oxygen species metabolic process
SNCA, LRRK2, PINK1, PRKN
 GO:2000377 4 / 27 60.2× 5.41e-7 5.12e-5 ✓ sig.
mitochondrion organization
VPS13C, LRRK2, PARK7, PINK1, PRKN, FMC1
 GO:0007005 6 / 130 18.7× 7.53e-7 6.72e-5 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hereditary parkinson disease Secondary parkinson disease 0.048 2 3.30e-4 7.83e-4 ✓ sig.
Hemiparkinsonism Parkinsonian-pyramidal syndrome 0.200 1 3.90e-4 8.67e-4 ✓ sig.
Hemiparkinsonism Thyroid hemiagenesis 0.200 1 3.90e-4 8.67e-4 ✓ sig.
Hemiparkinsonism Juvenile parkinsonism 0.167 1 5.84e-4 1.16e-3 ✓ sig.
Secondary parkinson disease Vesiculobullous skin disease 0.063 1 9.74e-4 1.67e-3 ✓ sig.
Hereditary parkinson disease Vesiculobullous skin disease 0.034 1 1.82e-3 2.68e-3 ✓ sig.
Parkinsonian-pyramidal syndrome Secondary parkinson disease 0.059 1 1.95e-3 2.83e-3 ✓ sig.
Hemiparkinsonism Secondary parkinson disease 0.056 1 2.92e-3 3.88e-3 ✓ sig.
Hereditary parkinson disease Juvenile parkinsonism 0.032 1 5.45e-3 6.63e-3 ✓ sig.