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 119

11 diseases · 18 shared-gene connections
11 Diseases
68 Unique genes
0.089 Avg. similarity score
Frontotemporal dementia with or without amyotrophic lateral sclerosis Most-connected disease (8 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 ⇵
Frontotemporal dementia with or without amyotrophic lateral sclerosis 8 8 12
Frontotemporal dementia with motor neuron disease 7 7 8
Frontotemporal dementia 6 6 60
frontotemporal dementia and/or amyotrophic lateral sclerosis 3 3 1
frontotemporal dementia and/or amyotrophic lateral sclerosis 1 2 2 1
frontotemporal dementia and/or amyotrophic lateral sclerosis 2 2 2 1
frontotemporal dementia and/or amyotrophic lateral sclerosis 5 2 2 1
frontotemporal dementia and/or amyotrophic lateral sclerosis 7 2 2 1
inclusion body myopathy with Paget disease of bone and frontotemporal dementia 2 2 1
amyotrophic lateral sclerosis type 6 1 1 1
ciliary dyskinesia, primary, 54 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
C9ORF72 4 / 11 Frontotemporal dementia, frontotemporal dementia and/or amyotrophic lateral sclerosis 1, Frontotemporal dementia with motor neuron disease, Frontotemporal dementia with or without amyotrophic lateral sclerosis
GRN 4 / 11 Frontotemporal dementia, frontotemporal dementia and/or amyotrophic lateral sclerosis, Frontotemporal dementia with motor neuron disease, Frontotemporal dementia with or without amyotrophic lateral sclerosis
CCNF 3 / 11 Frontotemporal dementia, frontotemporal dementia and/or amyotrophic lateral sclerosis 5, Frontotemporal dementia with or without amyotrophic lateral sclerosis
CHCHD10 3 / 11 frontotemporal dementia and/or amyotrophic lateral sclerosis 2, Frontotemporal dementia with motor neuron disease, Frontotemporal dementia with or without amyotrophic lateral sclerosis
CHMP2B 3 / 11 Frontotemporal dementia, frontotemporal dementia and/or amyotrophic lateral sclerosis 7, Frontotemporal dementia with or without amyotrophic lateral sclerosis
FUS 3 / 11 amyotrophic lateral sclerosis type 6, Frontotemporal dementia, Frontotemporal dementia with motor neuron disease
VCP 3 / 11 Frontotemporal dementia with motor neuron disease, Frontotemporal dementia with or without amyotrophic lateral sclerosis, inclusion body myopathy with Paget disease of bone and frontotemporal dementia
CFAP54 2 / 11 ciliary dyskinesia, primary, 54, Frontotemporal dementia
SQSTM1 2 / 11 Frontotemporal dementia with motor neuron disease, Frontotemporal dementia with or without amyotrophic lateral sclerosis
TARDBP 2 / 11 Frontotemporal dementia, Frontotemporal dementia with motor neuron disease
TBK1 2 / 11 Frontotemporal dementia with motor neuron disease, Frontotemporal dementia with or without amyotrophic lateral sclerosis
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 ⇵
Amyotrophic lateral sclerosis
ANG, CHMP2B, DCTN1, ERBB4, FUS, HNRNPA2B1, NDUFS1, OPTN, SEM1, SETX, TARDBP, TUBB4A
 KEGG 19 / 368 9.0× 1.25e-13 3.12e-11 ✓ sig.
Pathways of neurodegeneration - multiple diseases
CHMP2B, DCTN1, FUS, LRRK2, MAPT, NDUFS1, OPTN, PSEN1, SEM1, TARDBP, TUBB4A, SQSTM1
 KEGG 17 / 480 6.2× 1.11e-9 1.24e-7 ✓ sig.
Regulation of PLK1 Activity at G2/M Transition
CEP131, DCTN1, OPTN, TUBB4A, TUBA4A
 Reactome 5 / 88 9.9× 1.46e-4 3.05e-3 ✓ sig.
Nuclear signaling by ERBB4
APOE, ERBB4, PSEN1
 Reactome 3 / 24 21.8× 3.37e-4 5.87e-3 ✓ sig.
Highly sodium permeable postsynaptic acetylcholine nicotinic receptors
CHRNA4, CHRNB4
 Reactome 2 / 7 49.7× 6.71e-4 1.00e-2 ✓ sig.
Loss of Nlp from mitotic centrosomes
CEP131, DCTN1, TUBB4A, TUBA4A
 Reactome 4 / 70 9.9× 6.88e-4 1.02e-2 ✓ sig.
Loss of proteins required for interphase microtubule organization from the centrosome
CEP131, DCTN1, TUBB4A, TUBA4A
 Reactome 4 / 70 9.9× 6.88e-4 1.02e-2 ✓ sig.
Sealing of the nuclear envelope (NE) by ESCRT-III
CHMP2B, TUBB4A, TUBA4A
 Reactome 3 / 31 16.8× 7.27e-4 1.07e-2 ✓ sig.
AURKA Activation by TPX2
CEP131, DCTN1, TUBB4A, TUBA4A
 Reactome 4 / 73 9.5× 8.06e-4 1.16e-2 ✓ sig.
Parkinson disease
LRRK2, MAPT, NDUFS1, SEM1, TUBB4A, KIF5A, TUBA4A
 KEGG 7 / 268 4.5× 8.44e-4 1.19e-2 ✓ sig.
Highly calcium permeable nicotinic acetylcholine receptors
CHRNA4, CHRNB4
 Reactome 2 / 9 38.7× 1.14e-3 1.50e-2 ✓ sig.
Recruitment of mitotic centrosome proteins and complexes
CEP131, DCTN1, TUBB4A, TUBA4A
 Reactome 4 / 82 8.5× 1.25e-3 1.60e-2 ✓ sig.
Alzheimer disease
APOE, MAPT, NDUFS1, PSEN1, SEM1, TUBB4A, KIF5A, TUBA4A
 KEGG 8 / 388 3.6× 1.65e-3 1.99e-2 ✓ sig.
Recruitment of NuMA to mitotic centrosomes
CEP131, DCTN1, TUBB4A, TUBA4A
 Reactome 4 / 94 7.4× 2.06e-3 2.34e-2 ✓ sig.
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors
CHRNA4, CHRNB4
 Reactome 2 / 12 29.0× 2.07e-3 2.34e-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 ⇵
regulation of synaptic transmission, glutamatergic
LRRK2, MEF2C, PSEN1, UNC13A
 GO:0051966 4 / 33 32.8× 6.42e-6 3.66e-4 ✓ sig.
neuron cellular homeostasis
CHMP2B, DCTN1, PSEN1, TMEM106B
 GO:0070050 4 / 33 32.8× 6.42e-6 3.66e-4 ✓ sig.
maintenance of synapse structure
DCTN1, GRN, CHCHD10
 GO:0099558 3 / 12 67.7× 1.04e-5 5.35e-4 ✓ sig.
autophagy
CHMP2B, LRRK2, OPTN, PSEN1, SQSTM1, VCP, C9orf72
 GO:0006914 7 / 221 8.6× 1.70e-5 7.92e-4 ✓ sig.
locomotory exploration behavior
APOE, GRN, LRRK2
 GO:0035641 3 / 16 50.8× 2.61e-5 1.10e-3 ✓ sig.
astrocyte activation
MAPT, PSEN1, TREM2
 GO:0048143 3 / 17 47.8× 3.16e-5 1.27e-3 ✓ sig.
astrocyte activation involved in immune response
GRN, PSEN1
 GO:0002265 2 / 4 135× 8.02e-5 2.57e-3 ✓ sig.
cardiac muscle tissue regeneration
ERBB4, GATA4
 GO:0061026 2 / 4 135× 8.02e-5 2.57e-3 ✓ sig.
response to ischemia
CSF1R, MEF2C, TREM2, SQSTM1
 GO:0002931 4 / 63 17.2× 8.60e-5 2.71e-3 ✓ sig.
lysosome organization
GRN, LRRK2, TMEM106B, WASHC5
 GO:0007040 4 / 65 16.7× 9.73e-5 2.96e-3 ✓ sig.
synaptic transmission, cholinergic
APOE, CHRNA4, CHRNB4
 GO:0007271 3 / 25 32.5× 1.05e-4 3.12e-3 ✓ sig.
excitatory postsynaptic potential
CHRNA4, CHRNB4, LRRK2, MEF2C
 GO:0060079 4 / 69 15.7× 1.23e-4 3.53e-3 ✓ sig.
cellular response to lipoprotein particle stimulus
APOE, TREM2
 GO:0071402 2 / 5 108× 1.33e-4 3.75e-3 ✓ sig.
positive regulation of amyloid fibril formation
APOE, PSEN1
 GO:1905908 2 / 5 108× 1.33e-4 3.75e-3 ✓ sig.
microglial cell activation involved in immune response
GRN, TREM2
 GO:0002282 2 / 5 108× 1.33e-4 3.75e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Frontotemporal dementia with motor neuron disease Frontotemporal dementia with or without amyotrophic lateral sclerosis 0.400 6 1.40e-18 2.61e-17 ✓ sig.
Frontotemporal dementia Frontotemporal dementia with motor neuron disease 0.062 4 1.44e-8 1.21e-7 ✓ sig.
Frontotemporal dementia Frontotemporal dementia with or without amyotrophic lateral sclerosis 0.058 4 1.01e-7 7.45e-7 ✓ sig.
amyotrophic lateral sclerosis type 6 Frontotemporal dementia with motor neuron disease 0.111 1 5.20e-4 1.04e-3 ✓ sig.
frontotemporal dementia and/or amyotrophic lateral sclerosis Frontotemporal dementia with motor neuron disease 0.111 1 5.20e-4 1.04e-3 ✓ sig.
Frontotemporal dementia with motor neuron disease inclusion body myopathy with Paget disease of bone and frontotemporal dementia 0.111 1 5.20e-4 1.04e-3 ✓ sig.
frontotemporal dementia and/or amyotrophic lateral sclerosis 1 Frontotemporal dementia with motor neuron disease 0.111 1 5.20e-4 1.04e-3 ✓ sig.
frontotemporal dementia and/or amyotrophic lateral sclerosis 2 Frontotemporal dementia with motor neuron disease 0.111 1 5.20e-4 1.04e-3 ✓ sig.
Frontotemporal dementia with or without amyotrophic lateral sclerosis inclusion body myopathy with Paget disease of bone and frontotemporal dementia 0.077 1 7.79e-4 1.39e-3 ✓ sig.
frontotemporal dementia and/or amyotrophic lateral sclerosis 7 Frontotemporal dementia with or without amyotrophic lateral sclerosis 0.077 1 7.79e-4 1.39e-3 ✓ sig.
frontotemporal dementia and/or amyotrophic lateral sclerosis 5 Frontotemporal dementia with or without amyotrophic lateral sclerosis 0.077 1 7.79e-4 1.39e-3 ✓ sig.
frontotemporal dementia and/or amyotrophic lateral sclerosis 2 Frontotemporal dementia with or without amyotrophic lateral sclerosis 0.077 1 7.79e-4 1.39e-3 ✓ sig.
frontotemporal dementia and/or amyotrophic lateral sclerosis 1 Frontotemporal dementia with or without amyotrophic lateral sclerosis 0.077 1 7.79e-4 1.39e-3 ✓ sig.
frontotemporal dementia and/or amyotrophic lateral sclerosis Frontotemporal dementia with or without amyotrophic lateral sclerosis 0.077 1 7.79e-4 1.39e-3 ✓ sig.
Frontotemporal dementia frontotemporal dementia and/or amyotrophic lateral sclerosis 5 0.016 1 3.90e-3 4.94e-3 ✓ sig.
Frontotemporal dementia frontotemporal dementia and/or amyotrophic lateral sclerosis 7 0.016 1 3.90e-3 4.94e-3 ✓ sig.
Frontotemporal dementia frontotemporal dementia and/or amyotrophic lateral sclerosis 0.016 1 3.90e-3 4.94e-3 ✓ sig.
ciliary dyskinesia, primary, 54 Frontotemporal dementia 0.016 1 3.90e-3 4.94e-3 ✓ sig.