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Cluster 155

9 diseases · 14 shared-gene connections

9 Diseases

18 Unique genes

0.214 Avg. similarity score

Leukocyte disorders Most-connected disease (7 links)

Significant edges only (q < 0.05) Spacing Colour by

Disease Searched: Splenic 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.

Splenic disease Leukocyte disorders Conjunctivitis hypoplasminogenemia Laryngeal disease Congenital leukocyte adherence deficiency

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

Disease ⇵	Connections in cluster ⇵	Significant partners ⇵	Curated genes ⇵
Leukocyte disorders	7	7	3
Conjunctivitis	4	4	2
hypoplasminogenemia	4	4	1
Laryngeal disease	3	3	6
Splenic disease	3	3	9
Congenital leukocyte adherence deficiency	2	2	2
FAS-related autoimmune lymphoproliferative immune disorder	2	2	1
Leukocyte adhesion deficiency	2	2	3
Developmental delay with autism spectrum disorder	1	1	1

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

Gene ⇵	Member diseases ⇵	Linked diseases
PLG	5 / 9	Conjunctivitis, hypoplasminogenemia, Laryngeal disease, Leukocyte disorders and 1 more
FAS	3 / 9	FAS-related autoimmune lymphoproliferative immune disorder, Leukocyte disorders, Splenic disease
ITGB2	3 / 9	Congenital leukocyte adherence deficiency, Leukocyte adhesion deficiency, Leukocyte disorders
FERMT3	2 / 9	Congenital leukocyte adherence deficiency, Leukocyte adhesion deficiency
HERC2	2 / 9	Conjunctivitis, Developmental delay with autism spectrum disorder

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 ⇵
Aromatic amines can be N-hydroxylated or N-dealkylated by CYP1A2 CYP1A2	Reactome	1 / 1	667×	1.50e-3	1.92e-2 ✓ sig.
APC truncation mutants are not K63 polyubiquitinated APC	Reactome	1 / 1	667×	1.50e-3	1.92e-2 ✓ sig.
Defective SLC35C1 causes congenital disorder of glycosylation 2C (CDG2C) SLC35C1	Reactome	1 / 1	667×	1.50e-3	1.92e-2 ✓ sig.
Influenza A PLG, FAS, JAK2	KEGG	3 / 173	11.6×	2.04e-3	2.41e-2 ✓ sig.
Chemical carcinogenesis - receptor activation JAK2, AHR, CYP1A2	KEGG	3 / 215	9.3×	3.79e-3	3.73e-2 ✓ sig.
Leishmaniasis ITGB2, JAK2	KEGG	2 / 78	17.1×	5.96e-3	5.10e-2
Biosynthesis of protectins CYP1A2	Reactome	1 / 4	167×	5.98e-3	5.11e-2
FasL/ CD95L signaling FAS	Reactome	1 / 5	133×	7.47e-3	5.89e-2
Complement and coagulation cascades ITGB2, PLG	KEGG	2 / 88	15.2×	7.53e-3	5.91e-2
Caffeine metabolism CYP1A2	KEGG	1 / 6	111×	8.96e-3	6.62e-2
Biosynthesis of maresin-like SPMs CYP1A2	Reactome	1 / 6	111×	8.96e-3	6.62e-2
GDP-fucose biosynthesis SLC35C1	Reactome	1 / 6	111×	8.96e-3	6.62e-2
Staphylococcus aureus infection ITGB2, PLG	KEGG	2 / 99	13.5×	9.44e-3	6.85e-2
Aryl hydrocarbon receptor signalling AHR	Reactome	1 / 7	95.3×	1.04e-2	7.29e-2
Interleukin-4 and Interleukin-13 signaling ITGB2, JAK2	Reactome	2 / 108	12.4×	1.12e-2	7.59e-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 ⇵
cell adhesion FERMT3, ITGB2, CDH9, CNTN5, JAK2, APC	GO:0007155	6 / 665	9.4×	2.56e-5	1.11e-3 ✓ sig.
proteasome-mediated ubiquitin-dependent protein catabolic process HERC2, KLHL2, JAK2, APC	GO:0043161	4 / 343	12.1×	2.78e-4	6.58e-3 ✓ sig.
microglial cell activation ITGB2, JAK2	GO:0001774	2 / 28	74.2×	3.26e-4	7.35e-3 ✓ sig.
leukocyte cell-cell adhesion FERMT3, ITGB2	GO:0007159	2 / 33	62.9×	4.55e-4	9.28e-3 ✓ sig.
positive regulation of apoptotic signaling pathway FAS, JAK2	GO:2001235	2 / 37	56.1×	5.72e-4	1.08e-2 ✓ sig.
positive regulation of nitric oxide biosynthetic process ITGB2, JAK2	GO:0045429	2 / 42	49.4×	7.37e-4	1.29e-2 ✓ sig.
negative regulation of Notch signaling pathway HERC2, SLC35C1	GO:0045746	2 / 42	49.4×	7.37e-4	1.29e-2 ✓ sig.
toxin biosynthetic process CYP1A2	GO:0009403	1 / 1	1,038×	9.63e-4	1.52e-2 ✓ sig.
GDP-fucose import into Golgi lumen SLC35C1	GO:0036085	1 / 1	1,038×	9.63e-4	1.52e-2 ✓ sig.
nuclear receptor-mediated mineralocorticoid signaling pathway JAK2	GO:0031959	1 / 1	1,038×	9.63e-4	1.52e-2 ✓ sig.
symbiont-induced defense-related programmed cell death JAK2	GO:0034050	1 / 1	1,038×	9.63e-4	1.52e-2 ✓ sig.
interleukin-35-mediated signaling pathway JAK2	GO:0070757	1 / 1	1,038×	9.63e-4	1.52e-2 ✓ sig.
cell-cell adhesion ITGB2, CDH9, CNTN5	GO:0098609	3 / 218	14.3×	1.12e-3	1.68e-2 ✓ sig.
extrinsic apoptotic signaling pathway FAS, JAK2	GO:0097191	2 / 57	36.4×	1.36e-3	1.87e-2 ✓ sig.
tumor necrosis factor-mediated signaling pathway FAS, JAK2	GO:0033209	2 / 60	34.6×	1.50e-3	1.99e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵	Disease B ⇵	Similarity score ⇵	Shared genes ⇵	P-value ⇵	FDR q-value ⇵
Congenital leukocyte adherence deficiency	Leukocyte adhesion deficiency	0.500	2	2.53e-8	1.93e-7 ✓ sig.
Leukocyte disorders	Splenic disease	0.182	2	9.11e-7	5.37e-6 ✓ sig.
Conjunctivitis	Developmental delay with autism spectrum disorder	0.333	1	1.30e-4	3.93e-4 ✓ sig.
Conjunctivitis	hypoplasminogenemia	0.333	1	1.30e-4	3.93e-4 ✓ sig.
FAS-related autoimmune lymphoproliferative immune disorder	Leukocyte disorders	0.250	1	1.95e-4	5.35e-4 ✓ sig.
hypoplasminogenemia	Leukocyte disorders	0.250	1	1.95e-4	5.35e-4 ✓ sig.
Congenital leukocyte adherence deficiency	Leukocyte disorders	0.200	1	3.90e-4	8.67e-4 ✓ sig.
Conjunctivitis	Leukocyte disorders	0.200	1	3.90e-4	8.67e-4 ✓ sig.
hypoplasminogenemia	Laryngeal disease	0.143	1	3.90e-4	8.67e-4 ✓ sig.
Leukocyte adhesion deficiency	Leukocyte disorders	0.167	1	5.84e-4	1.16e-3 ✓ sig.
FAS-related autoimmune lymphoproliferative immune disorder	Splenic disease	0.100	1	5.84e-4	1.16e-3 ✓ sig.
hypoplasminogenemia	Splenic disease	0.100	1	5.84e-4	1.16e-3 ✓ sig.
Conjunctivitis	Laryngeal disease	0.125	1	7.79e-4	1.41e-3 ✓ sig.
Laryngeal disease	Leukocyte disorders	0.111	1	1.17e-3	1.90e-3 ✓ sig.

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