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Cluster 577

5 diseases · 7 shared-gene connections

5 Diseases

3 Unique genes

0.357 Avg. similarity score

Corticobasal syndrome Most-connected disease (4 links)

Significant edges only (q < 0.05) Spacing Colour by

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.

Corticobasal syndrome Autoinflammation with arthritis and vasculitis Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8 Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 Reticulate acropigmentation of kitamura

Member diseases (most connected first ‐ the cluster's core)

Disease ⇵	Connections in cluster ⇵	Significant partners ⇵	Curated genes ⇵
Corticobasal syndrome	4	4	3
Autoinflammation with arthritis and vasculitis	3	3	1
Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8	3	3	1
Frontotemporal dementia and/or amyotrophic lateral sclerosis 4	3	3	1
Reticulate acropigmentation of kitamura	1	1	1

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

Gene ⇵	Member diseases ⇵	Linked diseases
TBK1	4 / 5	Autoinflammation with arthritis and vasculitis, Corticobasal syndrome, Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8, Frontotemporal dementia and/or amyotrophic lateral sclerosis 4
ADAM10	2 / 5	Corticobasal syndrome, Reticulate acropigmentation of kitamura

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 ⇵
STAT6-mediated induction of chemokines TBK1	Reactome	1 / 3	1,334×	7.49e-4	9.09e-3 ✓ sig.
IRF3 mediated activation of type 1 IFN TBK1	Reactome	1 / 5	801×	1.25e-3	1.34e-2 ✓ sig.
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant ADAM10	Reactome	1 / 7	572×	1.75e-3	1.73e-2 ✓ sig.
TICAM1-dependent activation of IRF3/IRF7 TBK1	Reactome	1 / 12	334×	2.99e-3	2.54e-2 ✓ sig.
IRF3-mediated induction of type I IFN TBK1	Reactome	1 / 13	308×	3.24e-3	2.69e-2 ✓ sig.
TRAF3-dependent IRF activation pathway TBK1	Reactome	1 / 14	286×	3.49e-3	2.83e-2 ✓ sig.
Regulation of innate immune responses to cytosolic DNA TBK1	Reactome	1 / 14	286×	3.49e-3	2.83e-2 ✓ sig.
Constitutive Signaling by NOTCH1 HD Domain Mutants ADAM10	Reactome	1 / 15	267×	3.74e-3	2.98e-2 ✓ sig.
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon TBK1	Reactome	1 / 18	222×	4.49e-3	3.39e-2 ✓ sig.
NOTCH3 Activation and Transmission of Signal to the Nucleus ADAM10	Reactome	1 / 19	211×	4.74e-3	3.52e-2 ✓ sig.
Interleukin-37 signaling TBK1	Reactome	1 / 21	191×	5.24e-3	3.76e-2 ✓ sig.
Negative regulators of DDX58/IFIH1 signaling TBK1	Reactome	1 / 27	148×	6.73e-3	4.43e-2 ✓ sig.
TRAF6 mediated IRF7 activation TBK1	Reactome	1 / 29	138×	7.23e-3	4.64e-2 ✓ sig.
Constitutive Signaling by NOTCH1 PEST Domain Mutants ADAM10	Reactome	1 / 58	69.0×	1.44e-2	7.09e-2
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants ADAM10	Reactome	1 / 58	69.0×	1.44e-2	7.09e-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 ⇵
constitutive protein ectodomain proteolysis ADAM10	GO:0051089	1 / 1	6,229×	1.61e-4	4.34e-3 ✓ sig.
epidermal growth factor receptor ligand maturation ADAM10	GO:0038004	1 / 2	3,115×	3.21e-4	7.04e-3 ✓ sig.
regulation of vasculature development ADAM10	GO:1901342	1 / 2	3,115×	3.21e-4	7.04e-3 ✓ sig.
protein catabolic process at postsynapse ADAM10	GO:0140249	1 / 3	2,076×	4.82e-4	9.24e-3 ✓ sig.
dendritic cell proliferation TBK1	GO:0044565	1 / 3	2,076×	4.82e-4	9.24e-3 ✓ sig.
signaling receptor ligand precursor processing ADAM10	GO:0140448	1 / 6	1,038×	9.63e-4	1.42e-2 ✓ sig.
negative regulation of gene expression TBK1, ADAM10	GO:0010629	2 / 339	36.7×	9.73e-4	1.43e-2 ✓ sig.
positive regulation of xenophagy TBK1	GO:1904417	1 / 8	779×	1.28e-3	1.67e-2 ✓ sig.
positive regulation of TORC2 signaling TBK1	GO:1904515	1 / 8	779×	1.28e-3	1.67e-2 ✓ sig.
monocyte activation ADAM10	GO:0042117	1 / 9	692×	1.44e-3	1.79e-2 ✓ sig.
pore complex assembly ADAM10	GO:0046931	1 / 9	692×	1.44e-3	1.79e-2 ✓ sig.
regulation of metabolic process TBK1	GO:0019222	1 / 10	623×	1.60e-3	1.88e-2 ✓ sig.
T follicular helper cell differentiation TBK1	GO:0061470	1 / 11	566×	1.76e-3	1.99e-2 ✓ sig.
regulation of type I interferon production TBK1	GO:0032479	1 / 11	566×	1.76e-3	1.99e-2 ✓ sig.
postsynapse organization ADAM10	GO:0099173	1 / 13	479×	2.09e-3	2.17e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵	Disease B ⇵	Similarity score ⇵	Shared genes ⇵	P-value ⇵	FDR q-value ⇵
Autoinflammation with arthritis and vasculitis	Frontotemporal dementia and/or amyotrophic lateral sclerosis 4	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Autoinflammation with arthritis and vasculitis	Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8	Frontotemporal dementia and/or amyotrophic lateral sclerosis 4	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Autoinflammation with arthritis and vasculitis	Corticobasal syndrome	0.250	1	1.94e-4	4.41e-4 ✓ sig.
Corticobasal syndrome	Reticulate acropigmentation of kitamura	0.250	1	1.94e-4	4.41e-4 ✓ sig.
Corticobasal syndrome	Frontotemporal dementia and/or amyotrophic lateral sclerosis 4	0.250	1	1.94e-4	4.41e-4 ✓ sig.
Corticobasal syndrome	Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8	0.250	1	1.94e-4	4.41e-4 ✓ sig.

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