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 63

15 diseases · 44 shared-gene connections
15 Diseases
33 Unique genes
0.292 Avg. similarity score
Hyperkalemic periodic paralysis Most-connected disease (9 links)
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Disease Searched: Familial acute necrotizing encephalopathy 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 ⇵
Hyperkalemic periodic paralysis 9 9 3
Hypokalemic periodic paralysis, type 2 9 9 1
Myopathy, autosomal recessive 9 9 1
Potassium-aggravated myotonia 9 9 1
Myotonia congenita, atypical, acetazolamide-responsive 8 8 1
Paramyotonia congenita 8 8 2
Myotonia 7 7 3
Congenital myopathy 22b, severe fetal 6 6 1
Male reproductive organ cancer 5 5 17
Thyrotoxic periodic paralysis 5 5 13
Becker generalized myotonia 3 3 2
Congenital myotonia 3 3 1
Encephalopathy, acute, infection-induced, 3 3 3 1
Familial acute necrotizing encephalopathy 3 3 1
X-linked epilepsy with or without intellectual disability and dysmorphic features 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
SCN4A 10 / 15 Congenital myopathy 22b, severe fetal, Hyperkalemic periodic paralysis, Hypokalemic periodic paralysis, type 2, Male reproductive organ cancer and 6 more
CLCN1 4 / 15 Becker generalized myotonia, Congenital myotonia, Hyperkalemic periodic paralysis, Myotonia
RANBP2 4 / 15 Encephalopathy, acute, infection-induced, 3, Familial acute necrotizing encephalopathy, Hyperkalemic periodic paralysis, Paramyotonia congenita
GABRA3 2 / 15 Thyrotoxic periodic paralysis, X-linked epilepsy with or without intellectual disability and dysmorphic features
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 ⇵
GABA receptor activation
GABRA3, GABRG3
 Reactome 2 / 16 45.5× 8.58e-4 1.01e-2 ✓ sig.
GABAergic synapse
GABRA3, GABRG3, CACNA1S
 KEGG 3 / 89 12.3× 1.83e-3 1.78e-2 ✓ sig.
Defective SLC2A1 causes GLUT1 deficiency syndrome 1 (GLUT1DS1)
SLC2A1
 Reactome 1 / 1 364× 2.75e-3 2.39e-2 ✓ sig.
Nicotine addiction
GABRA3, GABRG3
 KEGG 2 / 41 17.8× 5.61e-3 3.94e-2 ✓ sig.
Phase 0 - rapid depolarisation
SCN4A, CACNA1S
 Reactome 2 / 44 16.5× 6.44e-3 4.31e-2 ✓ sig.
Retrograde endocannabinoid signaling
GABRA3, GABRG3, CACNA1S
 KEGG 3 / 149 7.3× 7.78e-3 4.87e-2 ✓ sig.
Lactose synthesis
SLC2A1
 Reactome 1 / 3 121× 8.22e-3 5.04e-2
Ficolins bind to repetitive carbohydrate structures on the target cell surface
FCN2
 Reactome 1 / 5 72.8× 1.37e-2 6.87e-2
Caffeine metabolism
XDH
 KEGG 1 / 6 60.7× 1.64e-2 7.63e-2
RUNX3 regulates CDKN1A transcription
ZFHX3
 Reactome 1 / 7 52.0× 1.91e-2 8.33e-2
Lectin pathway of complement activation
FCN2
 Reactome 1 / 8 45.5× 2.18e-2 9.00e-2
Vitamin C (ascorbate) metabolism
SLC2A1
 Reactome 1 / 8 45.5× 2.18e-2 9.00e-2
Insulin secretion
CACNA1S, SLC2A1
 KEGG 2 / 86 8.5× 2.32e-2 9.33e-2
Interferon gamma signaling
HLA-DQB1, TRIM2
 Reactome 2 / 87 8.4× 2.37e-2 9.46e-2
Morphine addiction
GABRA3, GABRG3
 KEGG 2 / 91 8.0× 2.57e-2 9.92e-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 ⇵
monoatomic ion transmembrane transport
SCN4A, CLCN1, GABRA3, GABRG3, CACNA1S, KCNJ18
 GO:0034220 6 / 404 8.4× 6.64e-5 2.28e-3 ✓ sig.
chloride transport
CLCN1, GABRA3, GABRG3
 GO:0006821 3 / 81 21.0× 3.90e-4 8.04e-3 ✓ sig.
muscle contraction
SCN4A, CLCN1, CACNA1S
 GO:0006936 3 / 85 20.0× 4.49e-4 8.83e-3 ✓ sig.
inhibitory synapse assembly
GABRA3, GABRG3
 GO:1904862 2 / 25 45.3× 8.84e-4 1.36e-2 ✓ sig.
monoatomic ion transport
SCN4A, CLCN1, GABRA3, GABRG3, CACNA1S, KCNJ18
 GO:0006811 6 / 667 5.1× 9.83e-4 1.45e-2 ✓ sig.
chloride transmembrane transport
CLCN1, GABRA3, GABRG3
 GO:1902476 3 / 114 14.9× 1.06e-3 1.51e-2 ✓ sig.
gamma-aminobutyric acid signaling pathway
GABRA3, GABRG3
 GO:0007214 2 / 30 37.8× 1.28e-3 1.67e-2 ✓ sig.
synaptic transmission, GABAergic
GABRA3, GABRG3
 GO:0051932 2 / 35 32.4× 1.73e-3 1.98e-2 ✓ sig.
regulation of skeletal muscle contraction by action potential
SCN4A
 GO:0100001 1 / 1 566× 1.77e-3 1.99e-2 ✓ sig.
hypoxanthine catabolic process
XDH
 GO:0009114 1 / 1 566× 1.77e-3 1.99e-2 ✓ sig.
xanthine catabolic process
XDH
 GO:0009115 1 / 1 566× 1.77e-3 1.99e-2 ✓ sig.
skeletal muscle adaptation
CACNA1S
 GO:0043501 1 / 1 566× 1.77e-3 1.99e-2 ✓ sig.
glycoRNA biosynthetic process
DTWD2
 GO:0141217 1 / 1 566× 1.77e-3 1.99e-2 ✓ sig.
photoreceptor cell maintenance
PCDH15, SLC2A1
 GO:0045494 2 / 45 25.2× 2.86e-3 2.55e-2 ✓ sig.
inosine catabolic process
XDH
 GO:0006148 1 / 2 283× 3.53e-3 2.82e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hyperkalemic periodic paralysis Paramyotonia congenita 0.500 2 2.50e-8 1.87e-7 ✓ sig.
Hyperkalemic periodic paralysis Myotonia 0.400 2 7.50e-8 5.34e-7 ✓ sig.
Myotonia congenita, atypical, acetazolamide-responsive Potassium-aggravated myotonia 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Hypokalemic periodic paralysis, type 2 Potassium-aggravated myotonia 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Hypokalemic periodic paralysis, type 2 Myopathy, autosomal recessive 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Hypokalemic periodic paralysis, type 2 Myotonia congenita, atypical, acetazolamide-responsive 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Encephalopathy, acute, infection-induced, 3 Familial acute necrotizing encephalopathy 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Myopathy, autosomal recessive Potassium-aggravated myotonia 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Congenital myopathy 22b, severe fetal Myotonia congenita, atypical, acetazolamide-responsive 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Congenital myopathy 22b, severe fetal Hypokalemic periodic paralysis, type 2 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Congenital myopathy 22b, severe fetal Myopathy, autosomal recessive 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Congenital myopathy 22b, severe fetal Potassium-aggravated myotonia 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Myopathy, autosomal recessive Myotonia congenita, atypical, acetazolamide-responsive 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Becker generalized myotonia Congenital myotonia 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Myotonia congenita, atypical, acetazolamide-responsive Paramyotonia congenita 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Hypokalemic periodic paralysis, type 2 Paramyotonia congenita 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Myopathy, autosomal recessive Paramyotonia congenita 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Familial acute necrotizing encephalopathy Paramyotonia congenita 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Encephalopathy, acute, infection-induced, 3 Paramyotonia congenita 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Congenital myopathy 22b, severe fetal Paramyotonia congenita 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Paramyotonia congenita Potassium-aggravated myotonia 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Hyperkalemic periodic paralysis Potassium-aggravated myotonia 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Hyperkalemic periodic paralysis Myopathy, autosomal recessive 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Hyperkalemic periodic paralysis Hypokalemic periodic paralysis, type 2 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Familial acute necrotizing encephalopathy Hyperkalemic periodic paralysis 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Encephalopathy, acute, infection-induced, 3 Hyperkalemic periodic paralysis 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Congenital myotonia Myotonia 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Congenital myotonia Hyperkalemic periodic paralysis 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Myotonia Myotonia congenita, atypical, acetazolamide-responsive 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Hypokalemic periodic paralysis, type 2 Myotonia 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Myopathy, autosomal recessive Myotonia 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Myotonia Potassium-aggravated myotonia 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Becker generalized myotonia Hyperkalemic periodic paralysis 0.200 1 3.87e-4 7.33e-4 ✓ sig.
Becker generalized myotonia Myotonia 0.200 1 3.87e-4 7.33e-4 ✓ sig.
Potassium-aggravated myotonia Thyrotoxic periodic paralysis 0.071 1 8.39e-4 1.34e-3 ✓ sig.
Myopathy, autosomal recessive Thyrotoxic periodic paralysis 0.071 1 8.39e-4 1.34e-3 ✓ sig.
Hypokalemic periodic paralysis, type 2 Thyrotoxic periodic paralysis 0.071 1 8.39e-4 1.34e-3 ✓ sig.
Myotonia congenita, atypical, acetazolamide-responsive Thyrotoxic periodic paralysis 0.071 1 8.39e-4 1.34e-3 ✓ sig.
Thyrotoxic periodic paralysis X-linked epilepsy with or without intellectual disability and dysmorphic features 0.071 1 8.39e-4 1.34e-3 ✓ sig.
Congenital myopathy 22b, severe fetal Male reproductive organ cancer 0.056 1 1.10e-3 1.65e-3 ✓ sig.
Male reproductive organ cancer Myotonia congenita, atypical, acetazolamide-responsive 0.056 1 1.10e-3 1.65e-3 ✓ sig.
Hypokalemic periodic paralysis, type 2 Male reproductive organ cancer 0.056 1 1.10e-3 1.65e-3 ✓ sig.
Male reproductive organ cancer Myopathy, autosomal recessive 0.056 1 1.10e-3 1.65e-3 ✓ sig.
Male reproductive organ cancer Potassium-aggravated myotonia 0.056 1 1.10e-3 1.65e-3 ✓ sig.