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Cluster 108

11 diseases · 23 shared-gene connections

11 Diseases

19 Unique genes

0.238 Avg. similarity score

Atypical hemolytic uremic syndrome Most-connected disease (6 links)

Significant edges only (q < 0.05) Spacing Colour by

Disease Searched: Doyne honeycomb retinal dystrophy 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.

Doyne honeycomb retinal dystrophy Atypical hemolytic uremic syndrome Factor h deficiency Genetic hemolytic uremic syndrome Panuveitis Thrombotic microangiopathy

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

Disease ⇵	Connections in cluster ⇵	Significant partners ⇵	Curated genes ⇵
Atypical hemolytic uremic syndrome	6	6	3
Factor h deficiency	6	6	1
Genetic hemolytic uremic syndrome	6	6	1
Panuveitis	6	6	2
Thrombotic microangiopathy	6	6	3
Central serous retinopathy	5	5	11
Doyne honeycomb retinal dystrophy	5	5	4
Factor i deficiency	3	3	1
Choroid diseases	1	1	1
Intellectual developmental disorder seizures cerebellar	1	1	1
Throat disease	1	1	3

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

Gene ⇵	Member diseases ⇵	Linked diseases
CFH	7 / 11	Atypical hemolytic uremic syndrome, Central serous retinopathy, Doyne honeycomb retinal dystrophy, Factor h deficiency and 3 more
CFI	4 / 11	Atypical hemolytic uremic syndrome, Doyne honeycomb retinal dystrophy, Factor i deficiency, Thrombotic microangiopathy
GATA5	2 / 11	Central serous retinopathy, Throat disease
IL10	2 / 11	Choroid diseases, Panuveitis
RORA	2 / 11	Central serous retinopathy, Intellectual developmental disorder seizures cerebellar

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 ⇵
Regulation of Complement cascade CFH, CFI, CD46	Reactome	3 / 47	40.3×	5.21e-5	1.34e-3 ✓ sig.
Complement and coagulation cascades CFH, CFI, CD46	KEGG	3 / 88	21.5×	3.38e-4	5.99e-3 ✓ sig.
Staphylococcus aureus infection CFH, IL10, CFI	KEGG	3 / 99	19.2×	4.78e-4	7.88e-3 ✓ sig.
Negative regulation of NOTCH4 signaling NOTCH4	Reactome	1 / 2	316×	3.16e-3	3.24e-2 ✓ sig.
NOTCH4 Activation and Transmission of Signal to the Nucleus NOTCH4	Reactome	1 / 2	316×	3.16e-3	3.24e-2 ✓ sig.
Inflammatory bowel disease IL10, RORA	KEGG	2 / 66	19.2×	4.79e-3	4.33e-2 ✓ sig.
Virion - Adenovirus CD46	KEGG	1 / 4	158×	6.31e-3	5.22e-2
STING mediated induction of host immune responses DDX41	Reactome	1 / 5	126×	7.89e-3	6.04e-2
Defective LFNG causes SCDO3 NOTCH4	Reactome	1 / 5	126×	7.89e-3	6.04e-2
Pre-NOTCH Processing in Golgi NOTCH4	Reactome	1 / 6	105×	9.46e-3	6.76e-2
Interleukin-4 and Interleukin-13 signaling IL10, RORA	Reactome	2 / 108	11.7×	1.24e-2	8.00e-2
CD163 mediating an anti-inflammatory response IL10	Reactome	1 / 9	70.2×	1.42e-2	8.63e-2
Tryptophan catabolism SLC7A5	Reactome	1 / 11	57.5×	1.73e-2	9.77e-2
Virion - Ebolavirus, Lyssavirus and Morbillivirus CD46	KEGG	1 / 12	52.7×	1.88e-2	1.03e-1
IRF3-mediated induction of type I IFN DDX41	Reactome	1 / 13	48.6×	2.04e-2	1.07e-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 ⇵
regulation of complement-dependent cytotoxicity CFH, IL10	GO:1903659	2 / 8	246×	2.73e-5	1.15e-3 ✓ sig.
negative regulation of autophagy WNK1, IL10, SLC7A5	GO:0010507	3 / 73	40.4×	5.30e-5	1.92e-3 ✓ sig.
negative regulation of heterotypic cell-cell adhesion WNK1, IL10	GO:0034115	2 / 11	179×	5.36e-5	1.93e-3 ✓ sig.
liver regeneration IL10, SLC7A5	GO:0097421	2 / 29	67.8×	3.91e-4	8.28e-3 ✓ sig.
complement activation CFH, CFI	GO:0006956	2 / 35	56.2×	5.71e-4	1.07e-2 ✓ sig.
complement activation, classical pathway CFI, CD46	GO:0006958	2 / 37	53.2×	6.39e-4	1.15e-2 ✓ sig.
response to low light intensity stimulus PRPH2	GO:0009645	1 / 1	984×	1.02e-3	1.55e-2 ✓ sig.
negative regulation of chronic inflammatory response to antigenic stimulus IL10	GO:0002875	1 / 1	984×	1.02e-3	1.55e-2 ✓ sig.
negative regulation of cytokine activity IL10	GO:0060302	1 / 1	984×	1.02e-3	1.55e-2 ✓ sig.
regulation of response to wounding IL10	GO:1903034	1 / 1	984×	1.02e-3	1.55e-2 ✓ sig.
regulation of complement activation, alternative pathway CFH	GO:0030451	1 / 1	984×	1.02e-3	1.55e-2 ✓ sig.
positive regulation of L-leucine import across plasma membrane SLC7A5	GO:1905534	1 / 1	984×	1.02e-3	1.55e-2 ✓ sig.
positive regulation of termination of RNA polymerase II transcription WNK1	GO:1904595	1 / 1	984×	1.02e-3	1.55e-2 ✓ sig.
tissue development GATA5, NOTCH4	GO:0009888	2 / 51	38.6×	1.21e-3	1.74e-2 ✓ sig.
sequestering of extracellular ligand from receptor CD46	GO:0035581	1 / 2	492×	2.03e-3	2.34e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵	Disease B ⇵	Similarity score ⇵	Shared genes ⇵	P-value ⇵	FDR q-value ⇵
Atypical hemolytic uremic syndrome	Thrombotic microangiopathy	0.400	2	7.59e-8	5.43e-7 ✓ sig.
Atypical hemolytic uremic syndrome	Doyne honeycomb retinal dystrophy	0.333	2	1.52e-7	1.03e-6 ✓ sig.
Doyne honeycomb retinal dystrophy	Thrombotic microangiopathy	0.333	2	1.52e-7	1.03e-6 ✓ sig.
Factor h deficiency	Genetic hemolytic uremic syndrome	0.500	1	6.49e-5	2.32e-4 ✓ sig.
Choroid diseases	Panuveitis	0.333	1	1.30e-4	3.91e-4 ✓ sig.
Factor h deficiency	Panuveitis	0.333	1	1.30e-4	3.91e-4 ✓ sig.
Genetic hemolytic uremic syndrome	Panuveitis	0.333	1	1.30e-4	3.91e-4 ✓ sig.
Atypical hemolytic uremic syndrome	Factor h deficiency	0.250	1	1.95e-4	5.32e-4 ✓ sig.
Atypical hemolytic uremic syndrome	Factor i deficiency	0.250	1	1.95e-4	5.32e-4 ✓ sig.
Factor h deficiency	Thrombotic microangiopathy	0.250	1	1.95e-4	5.32e-4 ✓ sig.
Factor i deficiency	Thrombotic microangiopathy	0.250	1	1.95e-4	5.32e-4 ✓ sig.
Genetic hemolytic uremic syndrome	Thrombotic microangiopathy	0.250	1	1.95e-4	5.32e-4 ✓ sig.
Atypical hemolytic uremic syndrome	Genetic hemolytic uremic syndrome	0.250	1	1.95e-4	5.32e-4 ✓ sig.
Doyne honeycomb retinal dystrophy	Genetic hemolytic uremic syndrome	0.200	1	2.60e-4	6.48e-4 ✓ sig.
Doyne honeycomb retinal dystrophy	Factor i deficiency	0.200	1	2.60e-4	6.48e-4 ✓ sig.
Doyne honeycomb retinal dystrophy	Factor h deficiency	0.200	1	2.60e-4	6.48e-4 ✓ sig.
Atypical hemolytic uremic syndrome	Panuveitis	0.200	1	3.90e-4	8.64e-4 ✓ sig.
Panuveitis	Thrombotic microangiopathy	0.200	1	3.90e-4	8.64e-4 ✓ sig.
Central serous retinopathy	Factor h deficiency	0.083	1	7.14e-4	1.33e-3 ✓ sig.
Central serous retinopathy	Genetic hemolytic uremic syndrome	0.083	1	7.14e-4	1.33e-3 ✓ sig.
Central serous retinopathy	Intellectual developmental disorder seizures cerebellar	0.083	1	7.14e-4	1.33e-3 ✓ sig.
Central serous retinopathy	Panuveitis	0.077	1	1.43e-3	2.22e-3 ✓ sig.
Central serous retinopathy	Throat disease	0.071	1	2.14e-3	3.04e-3 ✓ sig.

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