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 214

9 diseases · 15 shared-gene connections
9 Diseases
9 Unique genes
0.241 Avg. similarity score
Metachromatic leukodystrophy Most-connected disease (7 links)
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Disease Searched: Arylsulfatase a deficiency 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 ⇵
Metachromatic leukodystrophy 7 7 8
Multiple sulfatase deficiency 6 6 3
Mucopolysaccharidosis type 6 4 4 1
Mucopolysaccharidosis type vi (maroteaux-lamy) 4 4 1
Mucopolysaccharidosis vi (mps6) 4 4 1
Arylsulfatase a deficiency 2 2 1
Alexander disease 1 1 1
Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2 1 1 1
Sulfatidosis, juvenile, austin type 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
ARSB 5 / 9 Metachromatic leukodystrophy, Mucopolysaccharidosis type 6, Mucopolysaccharidosis type vi (maroteaux-lamy), Mucopolysaccharidosis vi (mps6) and 1 more
ARSA 3 / 9 Arylsulfatase a deficiency, Metachromatic leukodystrophy, Multiple sulfatase deficiency
GFAP 2 / 9 Alexander disease, Metachromatic leukodystrophy
LOC100130207 2 / 9 Multiple sulfatase deficiency, Sulfatidosis, juvenile, austin type
YARS1 2 / 9 Metachromatic leukodystrophy, Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2
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 ⇵
Glycosphingolipid metabolism
ARSA, ARSB, PSAP
 Reactome 3 / 46 87.0× 4.35e-6 1.47e-4 ✓ sig.
The activation of arylsulfatases
ARSA, ARSB
 Reactome 2 / 13 205× 3.88e-5 8.92e-4 ✓ sig.
Lysosome
ARSA, ARSB, PSAP
 KEGG 3 / 133 30.1× 1.06e-4 1.99e-3 ✓ sig.
Sphingolipid metabolism
ARSA, PSAP
 KEGG 2 / 54 49.4× 7.00e-4 8.64e-3 ✓ sig.
MPS VI - Maroteaux-Lamy syndrome
ARSB
 Reactome 1 / 1 1,334× 7.49e-4 9.09e-3 ✓ sig.
Neutrophil degranulation
ARSA, ARSB, PSAP
 Reactome 3 / 480 8.3× 4.45e-3 3.38e-2 ✓ sig.
CS/DS degradation
ARSB
 Reactome 1 / 14 95.3× 1.04e-2 5.84e-2
Glycosaminoglycan degradation
ARSB
 KEGG 1 / 19 70.2× 1.42e-2 7.00e-2
Cytosolic tRNA aminoacylation
YARS1
 Reactome 1 / 24 55.6× 1.78e-2 8.03e-2
Nuclear signaling by ERBB4
GFAP
 Reactome 1 / 24 55.6× 1.78e-2 8.03e-2
Aminoacyl-tRNA biosynthesis
YARS1
 KEGG 1 / 66 20.2× 4.84e-2 1.42e-1
Stimuli-sensing channels
CLCN1
 Reactome 1 / 79 16.9× 5.77e-2 1.57e-1
Peptide ligand-binding receptors
PSAP
 Reactome 1 / 106 12.6× 7.67e-2 1.85e-1
Platelet degranulation
PSAP
 Reactome 1 / 123 10.8× 8.85e-2 2.01e-1
JAK-STAT signaling pathway
GFAP
 KEGG 1 / 168 7.9× 1.19e-1 2.40e-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 ⇵
lysosomal transport
ARSB, PSAP
 GO:0007041 2 / 26 160× 6.66e-5 2.28e-3 ✓ sig.
positive regulation of Schwann cell proliferation
GFAP
 GO:0010625 1 / 1 2,076× 4.82e-4 9.24e-3 ✓ sig.
colon epithelial cell migration
ARSB
 GO:0061580 1 / 1 2,076× 4.82e-4 9.24e-3 ✓ sig.
positive regulation of beta-galactosidase activity
PSAP
 GO:1903771 1 / 1 2,076× 4.82e-4 9.24e-3 ✓ sig.
ganglioside GM1 transport to membrane
PSAP
 GO:1905572 1 / 1 2,076× 4.82e-4 9.24e-3 ✓ sig.
protein insertion into plasma membrane
MAL
 GO:0098737 1 / 1 2,076× 4.82e-4 9.24e-3 ✓ sig.
tyrosyl-tRNA aminoacylation
YARS1
 GO:0006437 1 / 2 1,038× 9.63e-4 1.42e-2 ✓ sig.
Schwann cell proliferation
GFAP
 GO:0014010 1 / 3 692× 1.44e-3 1.79e-2 ✓ sig.
intermediate filament-based process
GFAP
 GO:0045103 1 / 3 692× 1.44e-3 1.79e-2 ✓ sig.
membrane raft polarization
MAL
 GO:0001766 1 / 3 692× 1.44e-3 1.79e-2 ✓ sig.
neuron projection regeneration
GFAP
 GO:0031102 1 / 4 519× 1.93e-3 2.07e-2 ✓ sig.
protein localization to paranode region of axon
MAL
 GO:0002175 1 / 4 519× 1.93e-3 2.07e-2 ✓ sig.
regulation of neurotransmitter uptake
GFAP
 GO:0051580 1 / 5 415× 2.41e-3 2.32e-2 ✓ sig.
D-aspartate import across plasma membrane
GFAP
 GO:0070779 1 / 5 415× 2.41e-3 2.32e-2 ✓ sig.
regulation of chaperone-mediated autophagy
GFAP
 GO:1904714 1 / 5 415× 2.41e-3 2.32e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Metachromatic leukodystrophy Multiple sulfatase deficiency 0.200 2 7.00e-7 4.35e-6 ✓ sig.
Mucopolysaccharidosis type 6 Mucopolysaccharidosis type vi (maroteaux-lamy) 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Mucopolysaccharidosis type 6 Mucopolysaccharidosis vi (mps6) 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Mucopolysaccharidosis type vi (maroteaux-lamy) Mucopolysaccharidosis vi (mps6) 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Arylsulfatase a deficiency Multiple sulfatase deficiency 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Mucopolysaccharidosis type 6 Multiple sulfatase deficiency 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Mucopolysaccharidosis type vi (maroteaux-lamy) Multiple sulfatase deficiency 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Mucopolysaccharidosis vi (mps6) Multiple sulfatase deficiency 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Multiple sulfatase deficiency Sulfatidosis, juvenile, austin type 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Alexander disease Metachromatic leukodystrophy 0.111 1 5.17e-4 9.13e-4 ✓ sig.
Arylsulfatase a deficiency Metachromatic leukodystrophy 0.111 1 5.17e-4 9.13e-4 ✓ sig.
Metachromatic leukodystrophy Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2 0.111 1 5.17e-4 9.13e-4 ✓ sig.
Metachromatic leukodystrophy Mucopolysaccharidosis type 6 0.111 1 5.17e-4 9.13e-4 ✓ sig.
Metachromatic leukodystrophy Mucopolysaccharidosis type vi (maroteaux-lamy) 0.111 1 5.17e-4 9.13e-4 ✓ sig.
Metachromatic leukodystrophy Mucopolysaccharidosis vi (mps6) 0.111 1 5.17e-4 9.13e-4 ✓ sig.