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 271

8 diseases · 9 shared-gene connections
8 Diseases
119 Unique genes
0.047 Avg. similarity score
Tremor Most-connected disease (5 links)
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Disease Searched: Neurodevelopmental disorder with impaired speech and hyperkinetic movements 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 ⇵
Tremor 5 5 19
Essential tremor 4 4 100
Neuronal intranuclear inclusion disease 3 3 1
Oculopharyngodistal myopathy 2 2 5
Catatonia 1 1 1
Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction 1 1 1
Neurodevelopmental disorder with impaired speech and hyperkinetic movements 1 1 1
Retinal dystrophy and obesity 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
NOTCH2NLC 4 / 8 Essential tremor, Neuronal intranuclear inclusion disease, Oculopharyngodistal myopathy, Tremor
CHRM4 2 / 8 Catatonia, Tremor
DRD3 2 / 8 Essential tremor, Tremor
FUS 2 / 8 Essential tremor, Tremor
GEMIN5 2 / 8 Essential tremor, Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction
TENM4 2 / 8 Essential tremor, Tremor
TUB 2 / 8 Essential tremor, Retinal dystrophy and obesity
ZNF142 2 / 8 Neurodevelopmental disorder with impaired speech and hyperkinetic movements, Tremor
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 ⇵
Synthesis, secretion, and deacylation of Ghrelin
IGF1, SPCS3, ACHE
 Reactome 3 / 19 15.9× 8.19e-4 9.72e-3 ✓ sig.
Hormone signaling
DRD3, GNAI1, GNAO1, IGF1, MLN, PIK3R1, ADRB2, TRH
 KEGG 8 / 219 3.7× 1.49e-3 1.53e-2 ✓ sig.
Costimulation by the CD28 family
ICOS, PIK3R1
 Reactome 2 / 11 18.3× 5.05e-3 3.67e-2 ✓ sig.
Cholinergic synapse
CHRM4, GNAI1, GNAO1, PIK3R1, ACHE
 KEGG 5 / 115 4.4× 5.67e-3 3.97e-2 ✓ sig.
PLC beta mediated events
GNAI1, GNAO1
 Reactome 2 / 12 16.8× 6.02e-3 4.12e-2 ✓ sig.
Retrograde endocannabinoid signaling
GABRA1, GNAI1, GNAO1, NDUFA10, NDUFV2
 KEGG 5 / 149 3.4× 1.62e-2 7.60e-2
Signaling by Hippo
WWTR1, YWHAE
 Reactome 2 / 20 10.1× 1.65e-2 7.66e-2
Acetylation
NAT2
 Reactome 1 / 2 50.5× 1.97e-2 8.52e-2
Regulation of lipolysis in adipocytes
GNAI1, PIK3R1, ADRB2
 KEGG 3 / 59 5.1× 2.06e-2 8.74e-2
Long-term depression
GNAI1, GNAO1, IGF1
 KEGG 3 / 60 5.0× 2.16e-2 8.94e-2
Serotonergic synapse
GNAI1, GNAO1, CYP2D6, HTR1A
 KEGG 4 / 115 3.5× 2.73e-2 1.02e-1
The NLRP1 inflammasome
NLRP1
 Reactome 1 / 3 33.6× 2.94e-2 1.07e-1
Neuroactive ligand-receptor interaction
CHRM4, DRD3, GABRA1, MLN, ADORA2A, ADRB2, HTR1A, TRH
 KEGG 8 / 370 2.2× 3.06e-2 1.10e-1
Circadian Clock
NPAS2, PPARGC1A
 Reactome 2 / 28 7.2× 3.11e-2 1.10e-1
G-protein activation
GNAI1, GNAO1
 Reactome 2 / 28 7.2× 3.11e-2 1.10e-1

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

GO term ⇵ GO ID ⇵ Overlap genes ⇵ Fold enrichment ⇵ P-value ⇵ FDR q-value ⇵
adenylate cyclase-inhibiting serotonin receptor signaling pathway
GNAI1, GNAO1, HTR1A
 GO:0007198 3 / 10 47.1× 2.92e-5 1.23e-3 ✓ sig.
adenylate cyclase-modulating G protein-coupled receptor signaling pathway
DRD3, GNAI1, GNAO1, ADORA2A, ADRB2
 GO:0007188 5 / 57 13.8× 3.09e-5 1.28e-3 ✓ sig.
histamine metabolic process
HNMT, TRH
 GO:0001692 2 / 4 78.5× 2.39e-4 5.76e-3 ✓ sig.
locomotory behavior
DRD3, GNAO1, ADORA2A, ATP7A, ASL
 GO:0007626 5 / 99 7.9× 4.27e-4 8.53e-3 ✓ sig.
postsynaptic modulation of chemical synaptic transmission
GNAO1, IGF1, TRIO
 GO:0099170 3 / 25 18.8× 5.23e-4 9.81e-3 ✓ sig.
neuron projection morphogenesis
NYAP2, TRIO, ADORA2A, ATP7A
 GO:0048812 4 / 70 9.0× 1.04e-3 1.50e-2 ✓ sig.
presynaptic modulation of chemical synaptic transmission
HIP1, GIPC1, ADORA2A
 GO:0099171 3 / 37 12.7× 1.67e-3 1.94e-2 ✓ sig.
positive regulation of melanin biosynthetic process
GIPC1, ATP7A
 GO:0048023 2 / 10 31.4× 1.75e-3 1.99e-2 ✓ sig.
serotonin metabolic process
ATP7A, HTR1A
 GO:0042428 2 / 10 31.4× 1.75e-3 1.99e-2 ✓ sig.
positive regulation of D-glucose import
IGF1, PIK3R1, SLC1A2
 GO:0046326 3 / 38 12.4× 1.81e-3 2.02e-2 ✓ sig.
T follicular helper cell differentiation
ICOS, PIK3R1
 GO:0061470 2 / 11 28.6× 2.13e-3 2.19e-2 ✓ sig.
elastic fiber assembly
FBLN5, ATP7A
 GO:0048251 2 / 11 28.6× 2.13e-3 2.19e-2 ✓ sig.
response to alkaloid
DHX15, ADORA2A
 GO:0043279 2 / 11 28.6× 2.13e-3 2.19e-2 ✓ sig.
cell adhesion
CNTNAP5, CTNNA3, DSCAML1, FBLN5, IGSF11, LSAMP, NFASC, PCDHA1, PCDHA2, LRP12, ACHE
 GO:0007155 11 / 665 2.6× 3.47e-3 2.81e-2 ✓ sig.
prepulse inhibition
DRD3, ADORA2A
 GO:0060134 2 / 14 22.4× 3.48e-3 2.81e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Essential tremor Tremor 0.034 4 5.89e-6 3.25e-5 ✓ sig.
Neuronal intranuclear inclusion disease Oculopharyngodistal myopathy 0.167 1 3.23e-4 6.41e-4 ✓ sig.
Catatonia Tremor 0.050 1 1.23e-3 1.81e-3 ✓ sig.
Neurodevelopmental disorder with impaired speech and hyperkinetic movements Tremor 0.050 1 1.23e-3 1.81e-3 ✓ sig.
Neuronal intranuclear inclusion disease Tremor 0.050 1 1.23e-3 1.81e-3 ✓ sig.
Oculopharyngodistal myopathy Tremor 0.042 1 6.12e-3 7.20e-3 ✓ sig.
Essential tremor Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction 0.010 1 6.46e-3 7.56e-3 ✓ sig.
Essential tremor Neuronal intranuclear inclusion disease 0.010 1 6.46e-3 7.56e-3 ✓ sig.
Essential tremor Retinal dystrophy and obesity 0.010 1 6.46e-3 7.56e-3 ✓ sig.