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 59

15 diseases · 24 shared-gene connections
15 Diseases
48 Unique genes
0.099 Avg. similarity score
Hypomyelinating leukodystrophy Most-connected disease (13 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 ⇵
Hypomyelinating leukodystrophy 13 13 30
Leukodystrophy 8 8 26
Tremor-ataxia-central hypomyelination syndrome 5 5 2
POLR3A-related disorder 4 4 1
Wiedemann-rautenstrauch syndrome 4 4 1
POLR3B-related disorder 3 3 1
hypomyelinating leukodystrophy 9 2 2 1
leukodystrophy, hypomyelinating, 18 2 2 1
Developmental delay with dysmorphic facies and brain anomalies 1 1 1
VPS11-related neurological disorder 1 1 1
hypomyelinating leukodystrophy 5 1 1 1
leukodystrophy, hypomyelinating, 14 1 1 1
leukodystrophy, hypomyelinating, 17 1 1 1
leukodystrophy, hypomyelinating, 21 1 1 1
leukodystrophy, hypomyelinating, 22 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
POLR3A 5 / 15 Hypomyelinating leukodystrophy, Leukodystrophy, POLR3A-related disorder, Tremor-ataxia-central hypomyelination syndrome and 1 more
POLR3B 4 / 15 Hypomyelinating leukodystrophy, Leukodystrophy, POLR3B-related disorder, Tremor-ataxia-central hypomyelination syndrome
DEGS1 3 / 15 Hypomyelinating leukodystrophy, Leukodystrophy, leukodystrophy, hypomyelinating, 18
RARS1 3 / 15 Hypomyelinating leukodystrophy, hypomyelinating leukodystrophy 9, Leukodystrophy
AIMP2 2 / 15 Hypomyelinating leukodystrophy, leukodystrophy, hypomyelinating, 17
CLDN11 2 / 15 Hypomyelinating leukodystrophy, leukodystrophy, hypomyelinating, 22
HSPD1 2 / 15 Hypomyelinating leukodystrophy, Leukodystrophy
HYCC1 2 / 15 Hypomyelinating leukodystrophy, hypomyelinating leukodystrophy 5
POLR3K 2 / 15 Hypomyelinating leukodystrophy, leukodystrophy, hypomyelinating, 21
PYCR2 2 / 15 Hypomyelinating leukodystrophy, Leukodystrophy
TMEM163 2 / 15 Hypomyelinating leukodystrophy, Leukodystrophy
TMEM63A 2 / 15 Hypomyelinating leukodystrophy, Leukodystrophy
U2AF2 2 / 15 Developmental delay with dysmorphic facies and brain anomalies, Leukodystrophy
UFM1 2 / 15 Hypomyelinating leukodystrophy, leukodystrophy, hypomyelinating, 14
VPS11 2 / 15 Hypomyelinating leukodystrophy, VPS11-related neurological disorder
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 ⇵
Cytosolic tRNA aminoacylation
AIMP1, RARS1, AARS1, KARS1, EPRS1, AIMP2
 Reactome 6 / 24 62.6× 3.76e-10 4.72e-8 ✓ sig.
RNA polymerase
POLR1C, POLR3K, POLR3B, POLR3A, POLR1A
 KEGG 5 / 34 36.8× 2.10e-7 1.25e-5 ✓ sig.
Cytosolic sensors of pathogen-associated DNA
POLR1C, POLR3K, POLR3B, POLR3A
 Reactome 4 / 22 45.5× 1.56e-6 7.13e-5 ✓ sig.
RNA Polymerase III Transcription Initiation From Type 2 Promoter
POLR1C, POLR3K, POLR3B, POLR3A
 Reactome 4 / 27 37.1× 3.68e-6 1.48e-4 ✓ sig.
RNA Polymerase III Transcription Initiation From Type 3 Promoter
POLR1C, POLR3K, POLR3B, POLR3A
 Reactome 4 / 28 35.7× 4.29e-6 1.67e-4 ✓ sig.
RNA Polymerase III Transcription Initiation From Type 1 Promoter
POLR1C, POLR3K, POLR3B, POLR3A
 Reactome 4 / 28 35.7× 4.29e-6 1.67e-4 ✓ sig.
Sphingolipid metabolism
ARSA, DEGS1, GALC, HEXA
 KEGG 4 / 54 18.5× 6.13e-5 1.51e-3 ✓ sig.
Aminoacyl-tRNA biosynthesis
RARS1, AARS1, KARS1, EPRS1
 KEGG 4 / 66 15.2× 1.35e-4 2.86e-3 ✓ sig.
RNA Polymerase I Transcription Termination
POLR1C, ERCC2, POLR1A
 Reactome 3 / 32 23.5× 2.74e-4 4.99e-3 ✓ sig.
Cytosolic DNA-sensing pathway
POLR1C, POLR3K, POLR3B, POLR3A
 KEGG 4 / 83 12.1× 3.27e-4 5.75e-3 ✓ sig.
RNA Polymerase I Transcription Initiation
POLR1C, ERCC2, POLR1A
 Reactome 3 / 45 16.7× 7.56e-4 1.10e-2 ✓ sig.
Glycosphingolipid metabolism
ARSA, GALC, HEXA
 Reactome 3 / 46 16.3× 8.06e-4 1.16e-2 ✓ sig.
Defective SLC9A6 causes X-linked, syndromic mental retardation,, Christianson type (MRXSCH)
SLC9A6
 Reactome 1 / 1 250× 4.00e-3 3.77e-2 ✓ sig.
Defective HEXA causes GM2G1
HEXA
 Reactome 1 / 1 250× 4.00e-3 3.77e-2 ✓ sig.
RNA Polymerase I Promoter Escape
POLR1C, ERCC2, POLR1A
 Reactome 3 / 91 8.2× 5.69e-3 4.77e-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 ⇵
DNA-templated transcription
POLR1C, POLR3K, POLR3B, POLR3A, ERCC2, POLR1A
 GO:0006351 6 / 113 20.7× 4.27e-7 4.08e-5 ✓ sig.
tRNA aminoacylation for protein translation
RARS1, AARS1, KARS1, EPRS1
 GO:0006418 4 / 36 43.3× 2.12e-6 1.51e-4 ✓ sig.
protein import into mitochondrial intermembrane space
HSPD1, AIFM1
 GO:0045041 2 / 3 260× 1.94e-5 8.74e-4 ✓ sig.
lysosome organization
HEXA, TMEM63A, VPS18, TMEM106B
 GO:0007040 4 / 65 24.0× 2.31e-5 1.00e-3 ✓ sig.
myelination
TMEM163, GALC, HEXA, MAL
 GO:0042552 4 / 73 21.3× 3.66e-5 1.43e-3 ✓ sig.
organelle fusion
VPS11, VPS18
 GO:0048284 2 / 4 195× 3.86e-5 1.48e-3 ✓ sig.
translation
AIMP1, RARS1, AARS1, KARS1, EPRS1, AIMP2
 GO:0006412 6 / 310 7.5× 1.36e-4 3.80e-3 ✓ sig.
positive regulation of interferon-beta production
POLR3B, POLR3A, TOMM70
 GO:0032728 3 / 41 28.5× 1.58e-4 4.27e-3 ✓ sig.
regulation of SNARE complex assembly
VPS11, VPS18
 GO:0035542 2 / 12 64.9× 4.19e-4 8.50e-3 ✓ sig.
tRNA aminoacylation
AARS1, EPRS1
 GO:0043039 2 / 13 59.9× 4.95e-4 9.50e-3 ✓ sig.
transcription by RNA polymerase I
POLR1C, POLR1A
 GO:0006360 2 / 15 51.9× 6.64e-4 1.15e-2 ✓ sig.
endosomal vesicle fusion
VPS11, VPS18
 GO:0034058 2 / 15 51.9× 6.64e-4 1.15e-2 ✓ sig.
negative regulation of intracellular estrogen receptor signaling pathway
VPS11, VPS18
 GO:0033147 2 / 15 51.9× 6.64e-4 1.15e-2 ✓ sig.
response to toxic substance
GJC2, AIFM1, CNP
 GO:0009636 3 / 83 14.1× 1.27e-3 1.75e-2 ✓ sig.
positive regulation of macrophage activation
HSPD1, KARS1
 GO:0043032 2 / 21 37.1× 1.32e-3 1.78e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hypomyelinating leukodystrophy Leukodystrophy 0.163 8 1.14e-16 1.93e-15 ✓ sig.
Leukodystrophy Tremor-ataxia-central hypomyelination syndrome 0.074 2 2.74e-6 1.57e-5 ✓ sig.
Hypomyelinating leukodystrophy Tremor-ataxia-central hypomyelination syndrome 0.065 2 3.67e-6 2.06e-5 ✓ sig.
POLR3A-related disorder Wiedemann-rautenstrauch syndrome 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Tremor-ataxia-central hypomyelination syndrome Wiedemann-rautenstrauch syndrome 0.333 1 1.30e-4 3.90e-4 ✓ sig.
POLR3B-related disorder Tremor-ataxia-central hypomyelination syndrome 0.333 1 1.30e-4 3.90e-4 ✓ sig.
POLR3A-related disorder Tremor-ataxia-central hypomyelination syndrome 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Developmental delay with dysmorphic facies and brain anomalies Leukodystrophy 0.037 1 1.69e-3 2.51e-3 ✓ sig.
Leukodystrophy Wiedemann-rautenstrauch syndrome 0.037 1 1.69e-3 2.51e-3 ✓ sig.
hypomyelinating leukodystrophy 9 Leukodystrophy 0.037 1 1.69e-3 2.51e-3 ✓ sig.
Leukodystrophy POLR3B-related disorder 0.037 1 1.69e-3 2.51e-3 ✓ sig.
Leukodystrophy leukodystrophy, hypomyelinating, 18 0.037 1 1.69e-3 2.51e-3 ✓ sig.
Leukodystrophy POLR3A-related disorder 0.037 1 1.69e-3 2.51e-3 ✓ sig.
Hypomyelinating leukodystrophy Wiedemann-rautenstrauch syndrome 0.032 1 1.95e-3 2.81e-3 ✓ sig.
Hypomyelinating leukodystrophy VPS11-related neurological disorder 0.032 1 1.95e-3 2.81e-3 ✓ sig.
Hypomyelinating leukodystrophy POLR3A-related disorder 0.032 1 1.95e-3 2.81e-3 ✓ sig.
Hypomyelinating leukodystrophy leukodystrophy, hypomyelinating, 22 0.032 1 1.95e-3 2.81e-3 ✓ sig.
Hypomyelinating leukodystrophy leukodystrophy, hypomyelinating, 21 0.032 1 1.95e-3 2.81e-3 ✓ sig.
Hypomyelinating leukodystrophy leukodystrophy, hypomyelinating, 18 0.032 1 1.95e-3 2.81e-3 ✓ sig.
Hypomyelinating leukodystrophy leukodystrophy, hypomyelinating, 17 0.032 1 1.95e-3 2.81e-3 ✓ sig.
Hypomyelinating leukodystrophy leukodystrophy, hypomyelinating, 14 0.032 1 1.95e-3 2.81e-3 ✓ sig.
Hypomyelinating leukodystrophy hypomyelinating leukodystrophy 9 0.032 1 1.95e-3 2.81e-3 ✓ sig.
Hypomyelinating leukodystrophy hypomyelinating leukodystrophy 5 0.032 1 1.95e-3 2.81e-3 ✓ sig.
Hypomyelinating leukodystrophy POLR3B-related disorder 0.032 1 1.95e-3 2.81e-3 ✓ sig.