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 557

5 diseases · 9 shared-gene connections
5 Diseases
30 Unique genes
0.408 Avg. similarity score
Congenital hypothyroidism without goiter 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 ⇵
Congenital hypothyroidism without goiter 4 4 6
Congenital thyroid atrophy 4 4 6
Thyroid agenesis 4 4 7
Congenital hypothyroidism 3 3 18
Testicular disease 3 3 14

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

Gene ⇵ Member diseases ⇵ Linked diseases
IGSF1 5 / 5 Congenital hypothyroidism, Congenital hypothyroidism without goiter, Congenital thyroid atrophy, Testicular disease and 1 more
PAX8 5 / 5 Congenital hypothyroidism, Congenital hypothyroidism without goiter, Congenital thyroid atrophy, Testicular disease and 1 more
NKX2-5 4 / 5 Congenital hypothyroidism, Congenital hypothyroidism without goiter, Congenital thyroid atrophy, Thyroid agenesis
THRA 4 / 5 Congenital hypothyroidism, Congenital hypothyroidism without goiter, Congenital thyroid atrophy, Thyroid agenesis
TSHB 4 / 5 Congenital hypothyroidism, Congenital hypothyroidism without goiter, Congenital thyroid atrophy, Thyroid agenesis
TSHR 4 / 5 Congenital hypothyroidism, Congenital hypothyroidism without goiter, Congenital thyroid atrophy, Thyroid agenesis
SLC26A4 2 / 5 Congenital hypothyroidism, Thyroid agenesis
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 ⇵
Thyroid hormone synthesis
PAX8, SLC26A4, TSHR, TSHB, DUOX2, DUOXA2, IYD, SLC5A5, TPO
 KEGG 9 / 75 48.0× 1.13e-13 2.65e-11 ✓ sig.
Thyroxine biosynthesis
TSHB, DUOX2, IYD, SLC5A5, TPO
 Reactome 5 / 7 286× 1.43e-12 2.63e-10 ✓ sig.
Autoimmune thyroid disease
TSHR, TSHB, TPO, FASLG
 KEGG 4 / 54 29.7× 9.17e-6 2.71e-4 ✓ sig.
Multifunctional anion exchangers
SLC26A4, SLC26A7
 Reactome 2 / 9 89.0× 2.15e-4 3.47e-3 ✓ sig.
Glycoprotein hormones
TSHB, INHBB
 Reactome 2 / 12 66.7× 3.92e-4 5.53e-3 ✓ sig.
Hormone ligand-binding receptors
TSHR, TSHB
 Reactome 2 / 12 66.7× 3.92e-4 5.53e-3 ✓ sig.
Defective SLC26A4 causes Pendred syndrome (PDS)
SLC26A4
 Reactome 1 / 1 400× 2.50e-3 2.23e-2 ✓ sig.
Defective SLC5A5 causes thyroid dyshormonogenesis 1 (TDH1)
SLC5A5
 Reactome 1 / 1 400× 2.50e-3 2.23e-2 ✓ sig.
HSP90 chaperone cycle for steroid hormone receptors (SHR)
TUBB1, FKBP4
 Reactome 2 / 55 14.6× 8.25e-3 5.05e-2
Regulation of lipolysis in adipocytes
TSHR, TSHB
 KEGG 2 / 59 13.6× 9.45e-3 5.49e-2
Antagonism of Activin by Follistatin
INHBB
 Reactome 1 / 4 100× 9.96e-3 5.67e-2
HHAT G278V abrogates palmitoylation of Hh-Np
SHH
 Reactome 1 / 4 100× 9.96e-3 5.67e-2
Long-term potentiation
GRIN2B, PPP3CA
 KEGG 2 / 67 12.0× 1.21e-2 6.37e-2
FasL/ CD95L signaling
FASLG
 Reactome 1 / 5 80.1× 1.24e-2 6.49e-2
Amphetamine addiction
GRIN2B, PPP3CA
 KEGG 2 / 69 11.6× 1.28e-2 6.57e-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 ⇵
thyroid gland development
NKX2-5, PAX8, THRA, TUBB1, SHH, FOXE1, NKX2-1
 GO:0030878 7 / 30 145× 2.56e-14 1.64e-11 ✓ sig.
thyroid hormone generation
DUOX2, SLC26A7, SLC5A5, TPO, FOXE1
 GO:0006590 5 / 16 195× 3.24e-11 1.10e-8 ✓ sig.
iodide transport
SLC26A4, SLC26A7, SLC5A5
 GO:0015705 3 / 8 234× 2.08e-7 2.33e-5 ✓ sig.
thyroid-stimulating hormone signaling pathway
PAX8, TSHR
 GO:0038194 2 / 2 623× 2.49e-6 1.81e-4 ✓ sig.
apoptotic signaling pathway
INHBB, SHH, TNFSF12, FASLG
 GO:0097190 4 / 84 29.7× 9.52e-6 5.23e-4 ✓ sig.
cellular response to gonadotropin stimulus
PAX8, SLC5A5
 GO:0071371 2 / 7 178× 5.21e-5 1.90e-3 ✓ sig.
copper ion transport
FKBP4, ATP7B
 GO:0006825 2 / 11 113× 1.36e-4 3.84e-3 ✓ sig.
oxalate transport
SLC26A4, SLC26A7
 GO:0019532 2 / 11 113× 1.36e-4 3.84e-3 ✓ sig.
hormone biosynthetic process
DUOX2, TPO
 GO:0042446 2 / 12 104× 1.63e-4 4.38e-3 ✓ sig.
sulfate transmembrane transport
SLC26A4, SLC26A7
 GO:1902358 2 / 16 77.9× 2.95e-4 6.69e-3 ✓ sig.
prostate gland development
FKBP4, SHH
 GO:0030850 2 / 16 77.9× 2.95e-4 6.69e-3 ✓ sig.
epithelial tube branching involved in lung morphogenesis
SHH, NKX2-1
 GO:0060441 2 / 20 62.3× 4.65e-4 9.06e-3 ✓ sig.
cell-cell signaling
TSHR, TSHB, SHH, FASLG
 GO:0007267 4 / 234 10.6× 5.08e-4 9.60e-3 ✓ sig.
hydrogen peroxide catabolic process
DUOX2, TPO
 GO:0042744 2 / 21 59.3× 5.13e-4 9.67e-3 ✓ sig.
animal organ development
SHH, FOXE1, NKX2-1
 GO:0048513 3 / 102 18.3× 5.76e-4 1.05e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Congenital hypothyroidism without goiter Congenital thyroid atrophy 0.857 6 5.22e-23 8.37e-22 ✓ sig.
Congenital hypothyroidism without goiter Thyroid agenesis 0.750 6 3.65e-22 5.71e-21 ✓ sig.
Congenital thyroid atrophy Thyroid agenesis 0.750 6 3.65e-22 5.71e-21 ✓ sig.
Congenital hypothyroidism Thyroid agenesis 0.368 7 7.51e-22 1.16e-20 ✓ sig.
Congenital hypothyroidism Congenital thyroid atrophy 0.316 6 9.69e-19 1.36e-17 ✓ sig.
Congenital hypothyroidism Congenital hypothyroidism without goiter 0.316 6 9.69e-19 1.36e-17 ✓ sig.
Congenital thyroid atrophy Testicular disease 0.105 2 1.14e-5 6.11e-5 ✓ sig.
Congenital hypothyroidism without goiter Testicular disease 0.105 2 1.14e-5 6.11e-5 ✓ sig.
Testicular disease Thyroid agenesis 0.100 2 1.59e-5 8.41e-5 ✓ sig.