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 95

11 diseases · 18 shared-gene connections
11 Diseases
31 Unique genes
0.174 Avg. similarity score
Liddle syndrome Most-connected disease (6 links)
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Disease Searched: pseudohypoaldosteronism type 2D 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 ⇵
Liddle syndrome 6 6 4
Pseudohypoparathyroidism 5 5 13
Bronchiectasis 4 4 17
Juvenile hyperuricemic nephropathy 4 4 2
Tonne-kalscheuer syndrome 4 4 2
renal tubular dysgenesis of genetic origin 4 4 1
Malignant hypertension 3 3 3
pseudohypoaldosteronism, type IB1, autosomal recessive 3 3 1
congenital disorder of glycosylation, type 2v 1 1 1
pseudohypoaldosteronism type 2D 1 1 1
pseudohypoaldosteronism type 2E 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
REN 5 / 11 Juvenile hyperuricemic nephropathy, Liddle syndrome, Malignant hypertension, renal tubular dysgenesis of genetic origin and 1 more
SCNN1A 4 / 11 Bronchiectasis, Liddle syndrome, pseudohypoaldosteronism, type IB1, autosomal recessive, Pseudohypoparathyroidism
SCNN1B 3 / 11 Bronchiectasis, Liddle syndrome, Pseudohypoparathyroidism
SCNN1G 3 / 11 Bronchiectasis, Liddle syndrome, Pseudohypoparathyroidism
CUL3 2 / 11 pseudohypoaldosteronism type 2E, Pseudohypoparathyroidism
EDEM3 2 / 11 Bronchiectasis, congenital disorder of glycosylation, type 2v
KLHL3 2 / 11 pseudohypoaldosteronism type 2D, Pseudohypoparathyroidism
LTBR 2 / 11 Bronchiectasis, Pseudohypoparathyroidism
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 ⇵
Stimuli-sensing channels
SCNN1B, SCNN1A, SCNN1G, WNK1, WNK4
 Reactome 5 / 79 24.5× 1.61e-6 7.90e-5 ✓ sig.
Aldosterone-regulated sodium reabsorption
SCNN1B, SCNN1A, SCNN1G, NR3C2
 KEGG 4 / 38 40.8× 2.52e-6 1.16e-4 ✓ sig.
Parathyroid hormone synthesis, secretion and action
GNAS, WNK1, WNK4, PTH1R
 KEGG 4 / 115 13.5× 2.06e-4 4.10e-3 ✓ sig.
Cortisol synthesis and secretion
AGT, CYP17A1, GNAS
 KEGG 3 / 65 17.9× 6.10e-4 9.64e-3 ✓ sig.
Renin secretion
REN, AGT, GNAS
 KEGG 3 / 69 16.8× 7.27e-4 1.10e-2 ✓ sig.
Metabolism of Angiotensinogen to Angiotensins
REN, AGT
 Reactome 2 / 17 45.6× 8.56e-4 1.24e-2 ✓ sig.
Taste transduction
SCNN1B, SCNN1A, SCNN1G
 KEGG 3 / 86 13.5× 1.38e-3 1.80e-2 ✓ sig.
Renin-angiotensin system
REN, AGT
 KEGG 2 / 23 33.7× 1.58e-3 1.99e-2 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
ICAM1, TNF, AGT
 KEGG 3 / 101 11.5× 2.19e-3 2.53e-2 ✓ sig.
Hormone signaling
AGT, GNAS, PTH1R, GHSR
 KEGG 4 / 219 7.1× 2.30e-3 2.62e-2 ✓ sig.
NF-kappa B signaling pathway
ICAM1, TNF, LTBR
 KEGG 3 / 105 11.1× 2.44e-3 2.74e-2 ✓ sig.
Dilated cardiomyopathy
TNF, AGT, GNAS
 KEGG 3 / 105 11.1× 2.44e-3 2.74e-2 ✓ sig.
Defective CYP17A1 causes Adrenal hyperplasia 5 (AH5)
CYP17A1
 Reactome 1 / 1 387× 2.58e-3 2.84e-2 ✓ sig.
African trypanosomiasis
ICAM1, TNF
 KEGG 2 / 37 20.9× 4.06e-3 3.92e-2 ✓ sig.
Negative regulation of NOTCH4 signaling
NOTCH4
 Reactome 1 / 2 194× 5.16e-3 4.62e-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 blood pressure
SCNN1B, SCNN1A, SCNN1G, UMOD, REN, AGT, WNK1, WNK4
 GO:0008217 8 / 83 58.1× 7.78e-13 3.65e-10 ✓ sig.
multicellular organismal-level water homeostasis
CFTR, SCNN1B, SCNN1A, SCNN1G, UMOD
 GO:0050891 5 / 12 251× 7.03e-12 2.69e-9 ✓ sig.
renal sodium ion absorption
UMOD, AGT, CUL3, KLHL3, WNK4
 GO:0070294 5 / 21 144× 1.79e-10 4.92e-8 ✓ sig.
sensory perception of salty taste
SCNN1B, SCNN1A, SCNN1G
 GO:0050914 3 / 4 452× 1.65e-8 2.65e-6 ✓ sig.
sodium ion homeostasis
SCNN1B, SCNN1A, SCNN1G, UMOD
 GO:0055078 4 / 20 121× 2.95e-8 4.36e-6 ✓ sig.
potassium ion homeostasis
SCNN1B, UMOD, KLHL3, WNK1
 GO:0055075 4 / 21 115× 3.64e-8 5.18e-6 ✓ sig.
intracellular sodium ion homeostasis
SCNN1B, SCNN1A, SCNN1G, UMOD
 GO:0006883 4 / 22 110× 4.44e-8 6.16e-6 ✓ sig.
cellular response to acidic pH
SCNN1B, SCNN1A, SCNN1G, GNAS
 GO:0071468 4 / 22 110× 4.44e-8 6.16e-6 ✓ sig.
cellular response to aldosterone
SCNN1B, SCNN1A, SCNN1G
 GO:1904045 3 / 7 258× 1.44e-7 1.68e-5 ✓ sig.
cellular response to vasopressin
SCNN1B, SCNN1A, SCNN1G
 GO:1904117 3 / 8 226× 2.30e-7 2.51e-5 ✓ sig.
sensory perception of sour taste
SCNN1B, SCNN1A, SCNN1G
 GO:0050915 3 / 9 201× 3.45e-7 3.52e-5 ✓ sig.
monoatomic ion homeostasis
UMOD, KLHL3, WNK4
 GO:0050801 3 / 10 181× 4.92e-7 4.73e-5 ✓ sig.
intracellular chloride ion homeostasis
UMOD, WNK1, WNK4
 GO:0030644 3 / 10 181× 4.92e-7 4.73e-5 ✓ sig.
sodium ion transmembrane transport
SCNN1B, SCNN1A, SCNN1G, WNK1, WNK4
 GO:0035725 5 / 134 22.5× 2.57e-6 1.82e-4 ✓ sig.
regulation of blood volume by renin-angiotensin
REN, AGT
 GO:0002016 2 / 2 603× 2.66e-6 1.87e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Bronchiectasis Pseudohypoparathyroidism 0.148 4 7.22e-10 6.63e-9 ✓ sig.
Liddle syndrome Pseudohypoparathyroidism 0.200 3 1.88e-9 1.65e-8 ✓ sig.
Bronchiectasis Liddle syndrome 0.158 3 4.47e-9 3.78e-8 ✓ sig.
Juvenile hyperuricemic nephropathy renal tubular dysgenesis of genetic origin 0.333 1 1.30e-4 3.93e-4 ✓ sig.
renal tubular dysgenesis of genetic origin Tonne-kalscheuer syndrome 0.333 1 1.30e-4 3.93e-4 ✓ sig.
Malignant hypertension renal tubular dysgenesis of genetic origin 0.250 1 1.95e-4 5.35e-4 ✓ sig.
Juvenile hyperuricemic nephropathy Tonne-kalscheuer syndrome 0.250 1 2.60e-4 6.51e-4 ✓ sig.
Liddle syndrome renal tubular dysgenesis of genetic origin 0.200 1 2.60e-4 6.51e-4 ✓ sig.
Liddle syndrome pseudohypoaldosteronism, type IB1, autosomal recessive 0.200 1 2.60e-4 6.51e-4 ✓ sig.
Malignant hypertension Tonne-kalscheuer syndrome 0.200 1 3.90e-4 8.67e-4 ✓ sig.
Juvenile hyperuricemic nephropathy Malignant hypertension 0.200 1 3.90e-4 8.67e-4 ✓ sig.
Liddle syndrome Tonne-kalscheuer syndrome 0.167 1 5.19e-4 1.06e-3 ✓ sig.
Juvenile hyperuricemic nephropathy Liddle syndrome 0.167 1 5.19e-4 1.06e-3 ✓ sig.
pseudohypoaldosteronism type 2D Pseudohypoparathyroidism 0.071 1 8.44e-4 1.50e-3 ✓ sig.
pseudohypoaldosteronism type 2E Pseudohypoparathyroidism 0.071 1 8.44e-4 1.50e-3 ✓ sig.
pseudohypoaldosteronism, type IB1, autosomal recessive Pseudohypoparathyroidism 0.071 1 8.44e-4 1.50e-3 ✓ sig.
Bronchiectasis pseudohypoaldosteronism, type IB1, autosomal recessive 0.056 1 1.10e-3 1.83e-3 ✓ sig.
Bronchiectasis congenital disorder of glycosylation, type 2v 0.056 1 1.10e-3 1.83e-3 ✓ sig.