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Cluster 408

5 diseases · 5 shared-gene connections

5 Diseases

8 Unique genes

0.189 Avg. similarity score

Hyperammonemia Most-connected disease (4 links)

Significant edges only (q < 0.05) Spacing Colour by

Disease Searched: systemic lupus erythematosus, susceptibility to, 1 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.

systemic lupus erythematosus, susceptibility to, 1 Hyperammonemia Chromosome 22q11.2 deletion syndrome interstitial lung disease due to ABCA3 deficiency ornithine carbamoyltransferase deficiency

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

Disease ⇵	Connections in cluster ⇵	Significant partners ⇵	Curated genes ⇵
Hyperammonemia	4	4	8
Chromosome 22q11.2 deletion syndrome	2	2	1
interstitial lung disease due to ABCA3 deficiency	2	2	1
ornithine carbamoyltransferase deficiency	1	1	1
systemic lupus erythematosus, susceptibility to, 1	1	1	1

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

Gene ⇵	Member diseases ⇵	Linked diseases
ABCA3	3 / 5	Chromosome 22q11.2 deletion syndrome, Hyperammonemia, interstitial lung disease due to ABCA3 deficiency
OTC	2 / 5	Hyperammonemia, ornithine carbamoyltransferase deficiency
TLR5	2 / 5	Hyperammonemia, systemic lupus erythematosus, susceptibility to, 1

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 ⇵
Arginine biosynthesis CPS1, GLUD1, NAGS, OTC	KEGG	4 / 23	261×	7.12e-10	8.63e-8 ✓ sig.
Urea cycle CPS1, NAGS, OTC	Reactome	3 / 10	450×	2.32e-8	1.93e-6 ✓ sig.
Biosynthesis of amino acids CPS1, NAGS, OTC	KEGG	3 / 75	60.1×	1.28e-5	4.35e-4 ✓ sig.
Nitrogen metabolism CPS1, GLUD1	KEGG	2 / 17	177×	5.25e-5	1.39e-3 ✓ sig.
Alanine, aspartate and glutamate metabolism CPS1, GLUD1	KEGG	2 / 37	81.1×	2.56e-4	4.85e-3 ✓ sig.
Defective ABCA3 causes pulmonary surfactant metabolism dysfunction type 3 (SMDP3) ABCA3	Reactome	1 / 1	1,501×	6.66e-4	1.03e-2 ✓ sig.
Defective ABCA3 causes pulmonary surfactant metabolism dysfunction 3 (SMDP3) ABCA3	Reactome	1 / 1	1,501×	6.66e-4	1.03e-2 ✓ sig.
Toll Like Receptor 5 (TLR5) Cascade TLR5	Reactome	1 / 1	1,501×	6.66e-4	1.03e-2 ✓ sig.
MyD88 deficiency (TLR5) TLR5	Reactome	1 / 2	751×	1.33e-3	1.75e-2 ✓ sig.
Metabolic pathways CPS1, GLUD1, NAGS, OTC, TYMS	KEGG	5 / 1,563	4.8×	1.48e-3	1.90e-2 ✓ sig.
Carbon metabolism CPS1, GLUD1	KEGG	2 / 115	26.1×	2.45e-3	2.74e-2 ✓ sig.
IRAK4 deficiency (TLR5) TLR5	Reactome	1 / 4	375×	2.66e-3	2.91e-2 ✓ sig.
MyD88 cascade initiated on plasma membrane TLR5	Reactome	1 / 9	167×	5.98e-3	5.11e-2
Glutamate and glutamine metabolism GLUD1	Reactome	1 / 14	107×	9.29e-3	6.78e-2
ABC transporters in lipid homeostasis ABCA3	Reactome	1 / 18	83.4×	1.19e-2	7.90e-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 ⇵
urea cycle CPS1, NAGS, OTC	GO:0000050	3 / 12	584×	1.13e-8	1.89e-6 ✓ sig.
monoatomic anion homeostasis CPS1, OTC	GO:0055081	2 / 2	2,336×	1.60e-7	1.84e-5 ✓ sig.
L-arginine biosynthetic process NAGS, OTC	GO:0006526	2 / 4	1,168×	9.62e-7	8.18e-5 ✓ sig.
citrulline biosynthetic process CPS1, OTC	GO:0019240	2 / 4	1,168×	9.62e-7	8.18e-5 ✓ sig.
midgut development CPS1, OTC	GO:0007494	2 / 8	584×	4.48e-6	2.83e-4 ✓ sig.
glutamine metabolic process CPS1, GLUD1	GO:0006541	2 / 15	311×	1.68e-5	8.09e-4 ✓ sig.
response to zinc ion CPS1, OTC	GO:0010043	2 / 27	173×	5.60e-5	2.02e-3 ✓ sig.
amino acid metabolic process GLUD1, OTC	GO:0006520	2 / 37	126×	1.06e-4	3.27e-3 ✓ sig.
response to xenobiotic stimulus ABCA3, CPS1, OTC	GO:0009410	3 / 248	28.3×	1.23e-4	3.64e-3 ✓ sig.
response to glucocorticoid ABCA3, CPS1	GO:0051384	2 / 53	88.1×	2.19e-4	5.54e-3 ✓ sig.
carbamoyl phosphate biosynthetic process CPS1	GO:0070409	1 / 1	2,336×	4.28e-4	8.87e-3 ✓ sig.
L-ornithine catabolic process OTC	GO:0006593	1 / 1	2,336×	4.28e-4	8.87e-3 ✓ sig.
positive regulation of protein homooligomerization ABCA3	GO:0032464	1 / 1	2,336×	4.28e-4	8.87e-3 ✓ sig.
liver development CPS1, OTC	GO:0001889	2 / 87	53.7×	5.89e-4	1.10e-2 ✓ sig.
L-arginine biosynthetic process via ornithine OTC	GO:0042450	1 / 2	1,168×	8.56e-4	1.41e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵	Disease B ⇵	Similarity score ⇵	Shared genes ⇵	P-value ⇵	FDR q-value ⇵
Chromosome 22q11.2 deletion syndrome	interstitial lung disease due to ABCA3 deficiency	0.500	1	6.49e-5	2.33e-4 ✓ sig.
Chromosome 22q11.2 deletion syndrome	Hyperammonemia	0.111	1	5.20e-4	1.06e-3 ✓ sig.
Hyperammonemia	systemic lupus erythematosus, susceptibility to, 1	0.111	1	5.20e-4	1.06e-3 ✓ sig.
Hyperammonemia	ornithine carbamoyltransferase deficiency	0.111	1	5.20e-4	1.06e-3 ✓ sig.
Hyperammonemia	interstitial lung disease due to ABCA3 deficiency	0.111	1	5.20e-4	1.06e-3 ✓ sig.

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