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.

← Back to all clusters

Cluster 92

12 diseases · 17 shared-gene connections
12 Diseases
30 Unique genes
0.160 Avg. similarity score
Neurodegeneration with brain iron accumulation Most-connected disease (6 links)
Log in to save this analysis

Save This Analysis

Disease Searched: neurodegeneration with brain iron accumulation 4 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 ⇵
Neurodegeneration with brain iron accumulation 6 6 14
Hallervorden spatz syndrome 5 5 7
Palmoplantar keratoderma with congenital alopecia 5 5 1
Hallermanns syndrome 4 4 2
Greither disease 3 3 4
Bilateral microphthalmos 2 2 5
Erythrokeratodermia variabilis 2 2 10
Pantothenate kinase-associated neurodegeneration 2 2 1
neurodegeneration with brain iron accumulation 4 2 2 1
Carnitine acetyltransferase deficiency 1 1 2
hereditary spastic paraplegia 35 1 1 1
kufor-rakeb syndrome 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
GJA1 6 / 12 Bilateral microphthalmos, Erythrokeratodermia variabilis, Greither disease, Hallermanns syndrome and 2 more
C19ORF12 3 / 12 Hallervorden spatz syndrome, Neurodegeneration with brain iron accumulation, neurodegeneration with brain iron accumulation 4
PANK2 3 / 12 Hallervorden spatz syndrome, Neurodegeneration with brain iron accumulation, Pantothenate kinase-associated neurodegeneration
ATP13A2 2 / 12 kufor-rakeb syndrome, Neurodegeneration with brain iron accumulation
CHD6 2 / 12 Hallermanns syndrome, Hallervorden spatz syndrome
COASY 2 / 12 Hallervorden spatz syndrome, Neurodegeneration with brain iron accumulation
CRAT 2 / 12 Carnitine acetyltransferase deficiency, Neurodegeneration with brain iron accumulation
FA2H 2 / 12 hereditary spastic paraplegia 35, Neurodegeneration with brain iron accumulation
GJB3 2 / 12 Erythrokeratodermia variabilis, Greither disease
GJB4 2 / 12 Erythrokeratodermia variabilis, Greither disease
PERP 2 / 12 Erythrokeratodermia variabilis, Greither disease
PLA2G6 2 / 12 Hallervorden spatz syndrome, Neurodegeneration with brain iron accumulation
WDR45 2 / 12 Hallervorden spatz syndrome, Neurodegeneration with brain iron accumulation
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 ⇵
Golgi Associated Vesicle Biogenesis
AP1B1, AP1S1, FTL, FTH1
 Reactome 4 / 56 27.7× 1.21e-5 4.17e-4 ✓ sig.
Gap junction assembly
GJA1, GJB3, GJB4
 Reactome 3 / 18 64.6× 1.24e-5 4.24e-4 ✓ sig.
Iron uptake and transport
CP, FTL, FTH1
 Reactome 3 / 28 41.5× 4.88e-5 1.31e-3 ✓ sig.
Ferroptosis
CP, FTL, FTH1
 KEGG 3 / 42 27.7× 1.67e-4 3.49e-3 ✓ sig.
Coenzyme A biosynthesis
PANK2, COASY
 Reactome 2 / 8 96.9× 1.79e-4 3.68e-3 ✓ sig.
Porphyrin metabolism
CP, FTL, FTH1
 KEGG 3 / 46 25.3× 2.19e-4 4.30e-3 ✓ sig.
Nef mediated downregulation of MHC class I complex cell surface expression
AP1B1, AP1S1
 Reactome 2 / 10 77.5× 2.86e-4 5.33e-3 ✓ sig.
Pantothenate and CoA biosynthesis
PANK2, COASY
 KEGG 2 / 21 36.9× 1.31e-3 1.73e-2 ✓ sig.
Retinoid metabolism disease events
RBP4
 Reactome 1 / 1 387× 2.58e-3 2.84e-2 ✓ sig.
Lysosome Vesicle Biogenesis
AP1B1, AP1S1
 Reactome 2 / 35 22.1× 3.64e-3 3.62e-2 ✓ sig.
Defective SLC40A1 causes hemochromatosis 4 (HFE4) (macrophages)
CP
 Reactome 1 / 2 194× 5.16e-3 4.62e-2 ✓ sig.
Defective CP causes aceruloplasminemia (ACERULOP)
CP
 Reactome 1 / 2 194× 5.16e-3 4.62e-2 ✓ sig.
Sphingolipid de novo biosynthesis
KDSR, FA2H
 Reactome 2 / 43 18.0× 5.45e-3 4.81e-2 ✓ sig.
COPI-independent Golgi-to-ER retrograde traffic
RAB3GAP1, PLA2G6
 Reactome 2 / 51 15.2× 7.60e-3 5.95e-2
Regulation of gap junction activity
GJA1
 Reactome 1 / 3 129× 7.72e-3 6.01e-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 ⇵
intracellular iron ion homeostasis
CP, FTL, ATP13A2, FTH1
 GO:0006879 4 / 71 34.0× 5.57e-6 3.39e-4 ✓ sig.
basolateral protein secretion
AP1B1, AP1S1
 GO:0110010 2 / 5 241× 2.66e-5 1.15e-3 ✓ sig.
coenzyme A biosynthetic process
PANK2, COASY
 GO:0015937 2 / 10 121× 1.19e-4 3.54e-3 ✓ sig.
glutamate secretion
GJA1, BEST1
 GO:0014047 2 / 11 110× 1.45e-4 4.12e-3 ✓ sig.
cell communication
GJA1, GJB3, GJB4
 GO:0007154 3 / 80 22.6× 3.11e-4 7.15e-3 ✓ sig.
bone remodeling
GJA1, EPHA2
 GO:0046849 2 / 18 67.0× 4.01e-4 8.50e-3 ✓ sig.
melanosome assembly
AP1B1, AP1S1
 GO:1903232 2 / 19 63.5× 4.47e-4 9.19e-3 ✓ sig.
positive regulation of autophagosome assembly
RAB3GAP1, WDR45
 GO:2000786 2 / 23 52.4× 6.59e-4 1.19e-2 ✓ sig.
detection of light stimulus involved in visual perception
RBP4, BEST1
 GO:0050908 2 / 24 50.2× 7.19e-4 1.26e-2 ✓ sig.
platelet dense granule organization
AP1B1, AP1S1
 GO:0060155 2 / 25 48.2× 7.80e-4 1.33e-2 ✓ sig.
iron ion transport
FTL, FTH1
 GO:0006826 2 / 31 38.9× 1.20e-3 1.74e-2 ✓ sig.
positive regulation of atrial cardiac muscle cell action potential
TRPM4
 GO:1903949 1 / 1 603× 1.66e-3 2.10e-2 ✓ sig.
positive regulation of regulation of vascular associated smooth muscle cell membrane depolarization
TRPM4
 GO:1904199 1 / 1 603× 1.66e-3 2.10e-2 ✓ sig.
notochord cell development
EPHA2
 GO:0060035 1 / 1 603× 1.66e-3 2.10e-2 ✓ sig.
microtubule-based transport
GJA1
 GO:0099111 1 / 1 603× 1.66e-3 2.10e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hallervorden spatz syndrome Neurodegeneration with brain iron accumulation 0.294 5 5.83e-15 8.30e-14 ✓ sig.
Erythrokeratodermia variabilis Greither disease 0.364 4 8.97e-14 1.16e-12 ✓ sig.
Hallermanns syndrome Hallervorden spatz syndrome 0.250 2 1.77e-7 1.18e-6 ✓ sig.
Hallermanns syndrome Palmoplantar keratoderma with congenital alopecia 0.333 1 1.30e-4 3.93e-4 ✓ sig.
Greither disease Palmoplantar keratoderma with congenital alopecia 0.200 1 2.60e-4 6.51e-4 ✓ sig.
Bilateral microphthalmos Palmoplantar keratoderma with congenital alopecia 0.167 1 3.25e-4 7.71e-4 ✓ sig.
Hallervorden spatz syndrome neurodegeneration with brain iron accumulation 4 0.125 1 4.55e-4 9.73e-4 ✓ sig.
Hallervorden spatz syndrome Pantothenate kinase-associated neurodegeneration 0.125 1 4.55e-4 9.73e-4 ✓ sig.
Hallervorden spatz syndrome Palmoplantar keratoderma with congenital alopecia 0.125 1 4.55e-4 9.73e-4 ✓ sig.
Greither disease Hallermanns syndrome 0.167 1 5.19e-4 1.06e-3 ✓ sig.
Bilateral microphthalmos Hallermanns syndrome 0.143 1 6.49e-4 1.24e-3 ✓ sig.
Erythrokeratodermia variabilis Palmoplantar keratoderma with congenital alopecia 0.091 1 6.49e-4 1.24e-3 ✓ sig.
hereditary spastic paraplegia 35 Neurodegeneration with brain iron accumulation 0.067 1 9.09e-4 1.58e-3 ✓ sig.
kufor-rakeb syndrome Neurodegeneration with brain iron accumulation 0.067 1 9.09e-4 1.58e-3 ✓ sig.
Neurodegeneration with brain iron accumulation neurodegeneration with brain iron accumulation 4 0.067 1 9.09e-4 1.58e-3 ✓ sig.
Neurodegeneration with brain iron accumulation Pantothenate kinase-associated neurodegeneration 0.067 1 9.09e-4 1.58e-3 ✓ sig.
Carnitine acetyltransferase deficiency Neurodegeneration with brain iron accumulation 0.063 1 1.82e-3 2.68e-3 ✓ sig.