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 410

5 diseases · 5 shared-gene connections
5 Diseases
11 Unique genes
0.155 Avg. similarity score
Bartter syndrome Most-connected disease (4 links)
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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.

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

Disease ⇵ Connections in cluster ⇵ Significant partners ⇵ Curated genes ⇵
Bartter syndrome 4 4 9
Gitelman syndrome 2 2 6
obsolete antenatal Bartter syndrome 2 2 1
Bartter disease type 2 1 1 1
Bartter disease type 5 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
SLC12A1 3 / 5 Bartter syndrome, Gitelman syndrome, obsolete antenatal Bartter syndrome
CASR 2 / 5 Bartter syndrome, Gitelman syndrome
CLCNKB 2 / 5 Bartter syndrome, Gitelman syndrome
KCNJ1 2 / 5 Bartter disease type 2, Bartter syndrome
MAGED2 2 / 5 Bartter disease type 5, Bartter syndrome
SLC12A3 2 / 5 Bartter syndrome, Gitelman syndrome
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 ⇵
Cation-coupled Chloride cotransporters
SLC12A1, SLC12A3
 Reactome 2 / 7 312× 1.60e-5 4.96e-4 ✓ sig.
Stimuli-sensing channels
BSND, CLCNKB, CLCNKA
 Reactome 3 / 79 41.5× 4.35e-5 1.14e-3 ✓ sig.
Defective SLC17A5 causes Salla disease (SD) and ISSD
SLC17A5
 Reactome 1 / 1 1,092× 9.16e-4 1.27e-2 ✓ sig.
MPS I - Hurler syndrome
IDUA
 Reactome 1 / 1 1,092× 9.16e-4 1.27e-2 ✓ sig.
Defective SLC12A1 causes Bartter syndrome 1 (BS1)
SLC12A1
 Reactome 1 / 1 1,092× 9.16e-4 1.27e-2 ✓ sig.
Defective SLC12A3 causes Gitelman syndrome (GS)
SLC12A3
 Reactome 1 / 1 1,092× 9.16e-4 1.27e-2 ✓ sig.
Potassium transport channels
KCNJ1
 Reactome 1 / 3 364× 2.75e-3 2.89e-2 ✓ sig.
Parathyroid hormone synthesis, secretion and action
CASR, SLC12A3
 KEGG 2 / 115 19.0× 4.72e-3 4.22e-2 ✓ sig.
Lysosome
IDUA, SLC17A5
 KEGG 2 / 133 16.4× 6.27e-3 5.08e-2
Organic anion transporters
SLC17A5
 Reactome 1 / 10 109× 9.12e-3 6.50e-2
CS/DS degradation
IDUA
 Reactome 1 / 14 78.0× 1.28e-2 7.89e-2
Metabolism of Angiotensinogen to Angiotensins
REN
 Reactome 1 / 17 64.2× 1.55e-2 8.86e-2
Glycosaminoglycan degradation
IDUA
 KEGG 1 / 19 57.5× 1.73e-2 9.50e-2
HS-GAG degradation
IDUA
 Reactome 1 / 22 49.6× 2.00e-2 1.03e-1
Renin-angiotensin system
REN
 KEGG 1 / 23 47.5× 2.09e-2 1.05e-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 ⇵
chloride transmembrane transport
SLC12A1, BSND, CASR, CLCNKB, SLC12A3, CLCNKA
 GO:1902476 6 / 114 89.4× 2.03e-11 6.94e-9 ✓ sig.
renal sodium ion absorption
KCNJ1, MAGED2, CLCNKB, SLC12A3
 GO:0070294 4 / 21 324× 3.87e-10 9.54e-8 ✓ sig.
monoatomic ion transport
KCNJ1, SLC12A1, CLCNKB, SLC12A3, CLCNKA, SLC17A5
 GO:0006811 6 / 667 15.3× 8.02e-7 6.93e-5 ✓ sig.
potassium ion import across plasma membrane
KCNJ1, SLC12A1, SLC12A3
 GO:1990573 3 / 46 111× 2.27e-6 1.59e-4 ✓ sig.
transmembrane transport
SLC12A1, CLCNKB, SLC12A3, CLCNKA, SLC17A5
 GO:0055085 5 / 557 15.2× 9.20e-6 4.90e-4 ✓ sig.
transepithelial chloride transport
CLCNKB, CLCNKA
 GO:0030321 2 / 9 378× 1.13e-5 5.73e-4 ✓ sig.
chloride transport
BSND, CLCNKB, CLCNKA
 GO:0006821 3 / 81 62.9× 1.26e-5 6.26e-4 ✓ sig.
renal absorption
CLCNKB, CLCNKA
 GO:0070293 2 / 11 309× 1.73e-5 8.00e-4 ✓ sig.
chloride ion homeostasis
SLC12A1, SLC12A3
 GO:0055064 2 / 13 261× 2.45e-5 1.05e-3 ✓ sig.
sodium ion homeostasis
SLC12A1, SLC12A3
 GO:0055078 2 / 20 170× 5.95e-5 2.04e-3 ✓ sig.
monoatomic ion transmembrane transport
KCNJ1, SLC12A1, CLCNKB, CLCNKA
 GO:0034220 4 / 404 16.8× 6.30e-5 2.14e-3 ✓ sig.
potassium ion homeostasis
SLC12A1, SLC12A3
 GO:0055075 2 / 21 162× 6.58e-5 2.21e-3 ✓ sig.
cell volume homeostasis
SLC12A1, SLC12A3
 GO:0006884 2 / 27 126× 1.10e-4 3.23e-3 ✓ sig.
heparin proteoglycan catabolic process
IDUA
 GO:0030211 1 / 1 1,699× 5.89e-4 1.07e-2 ✓ sig.
sialic acid transport
SLC17A5
 GO:0015739 1 / 1 1,699× 5.89e-4 1.07e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Bartter syndrome Gitelman syndrome 0.333 4 8.07e-13 1.04e-11 ✓ sig.
Gitelman syndrome obsolete antenatal Bartter syndrome 0.143 1 3.90e-4 8.52e-4 ✓ sig.
Bartter disease type 2 Bartter syndrome 0.100 1 5.84e-4 1.14e-3 ✓ sig.
Bartter disease type 5 Bartter syndrome 0.100 1 5.84e-4 1.14e-3 ✓ sig.
Bartter syndrome obsolete antenatal Bartter syndrome 0.100 1 5.84e-4 1.14e-3 ✓ sig.