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 399

5 diseases · 5 shared-gene connections
5 Diseases
128 Unique genes
0.051 Avg. similarity score
Corneal ulcer Most-connected disease (3 links)
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Disease Searched: Proliferative diabetic retinopathy 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 ⇵
Corneal ulcer 3 3 9
Eye disease 2 2 94
Proliferative diabetic retinopathy 2 2 36
retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome 2 2 1
C syndrome 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
ALPK1 3 / 5 Corneal ulcer, Eye disease, retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome
UTRN 3 / 5 Corneal ulcer, Eye disease, Proliferative diabetic retinopathy
CCBE1 2 / 5 Corneal ulcer, Eye disease
CD96 2 / 5 C syndrome, Proliferative diabetic retinopathy
KCNQ5 2 / 5 Eye disease, Proliferative diabetic retinopathy
NTF4 2 / 5 Corneal ulcer, Eye disease
RBFOX1 2 / 5 Eye disease, Proliferative diabetic retinopathy
RDX 2 / 5 Corneal ulcer, Eye disease
SERPINF1 2 / 5 Corneal ulcer, Proliferative diabetic retinopathy
SLC9A9 2 / 5 Corneal ulcer, Eye disease
UBE2V2 2 / 5 Corneal ulcer, Eye disease
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 ⇵
The canonical retinoid cycle in rods (twilight vision)
RDH5, LRAT, RLBP1, RPE65
 Reactome 4 / 20 18.8× 5.23e-5 1.39e-3 ✓ sig.
Graft-versus-host disease
HLA-C, HLA-DQA1, HLA-DQB1, IL6, HLA-B
 KEGG 5 / 45 10.4× 1.10e-4 2.51e-3 ✓ sig.
Defective ACTH causes Obesity and Pro-opiomelanocortinin deficiency (POMCD)
MC2R, POMC
 Reactome 2 / 2 93.8× 1.13e-4 2.56e-3 ✓ sig.
Herpes simplex virus 1 infection
HLA-C, HLA-DQA1, HLA-DQB1, IL6, JAK2, CCL2, HLA-B, SRSF6, STAT2
 KEGG 9 / 182 4.6× 1.40e-4 3.03e-3 ✓ sig.
MET activates PTK2 signaling
COL24A1, COL5A1, LAMA2, LAMB1
 Reactome 4 / 30 12.5× 2.72e-4 5.11e-3 ✓ sig.
Retinoid cycle disease events
RDH5, LRAT, RLBP1
 Reactome 3 / 13 21.7× 3.13e-4 5.71e-3 ✓ sig.
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
GNB3, TCF7L2, GRP
 Reactome 3 / 14 20.1× 3.95e-4 6.88e-3 ✓ sig.
Allograft rejection
HLA-C, HLA-DQA1, HLA-DQB1, HLA-B
 KEGG 4 / 39 9.6× 7.59e-4 1.14e-2 ✓ sig.
Viral myocarditis
HLA-C, HLA-DQA1, HLA-DQB1, LAMA2, HLA-B
 KEGG 5 / 70 6.7× 8.84e-4 1.27e-2 ✓ sig.
Kaposi sarcoma-associated herpesvirus infection
GNB3, HLA-C, IL6, JAK2, MICA, TCF7L2, HLA-B, STAT2
 KEGG 8 / 196 3.8× 1.17e-3 1.59e-2 ✓ sig.
Type I diabetes mellitus
HLA-C, HLA-DQA1, HLA-DQB1, HLA-B
 KEGG 4 / 44 8.5× 1.20e-3 1.62e-2 ✓ sig.
Interferon gamma signaling
HLA-C, HLA-DQA1, HLA-DQB1, JAK2, HLA-B
 Reactome 5 / 87 5.4× 2.34e-3 2.65e-2 ✓ sig.
Autoimmune thyroid disease
HLA-C, HLA-DQA1, HLA-DQB1, HLA-B
 KEGG 4 / 54 7.0× 2.58e-3 2.84e-2 ✓ sig.
Endosomal/Vacuolar pathway
HLA-C, HLA-B
 Reactome 2 / 8 23.5× 3.03e-3 3.17e-2 ✓ sig.
Ca2+ activated K+ channels
KCNMA1, KCNN3
 Reactome 2 / 9 20.9× 3.86e-3 3.78e-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 ⇵
vitamin A metabolic process
LRAT, RLBP1, RPE65
 GO:0006776 3 / 7 62.6× 1.08e-5 5.73e-4 ✓ sig.
visual perception
EFEMP1, GJD2, RDH5, RGR, TYR, LRAT, RLBP1, RPE65
 GO:0007601 8 / 215 5.4× 1.18e-4 3.53e-3 ✓ sig.
retinoid metabolic process
RDH5, LRAT, LRP2, RPE65
 GO:0001523 4 / 38 15.4× 1.29e-4 3.78e-3 ✓ sig.
negative regulation of defense response
MICA, PPARG
 GO:0031348 2 / 3 97.3× 1.39e-4 3.99e-3 ✓ sig.
camera-type eye development
BMP4, EFEMP1, PRSS56, RPGRIP1L, RPE65
 GO:0043010 5 / 74 9.9× 1.54e-4 4.31e-3 ✓ sig.
regulation of hormone metabolic process
GNB3, TCF7L2
 GO:0032350 2 / 4 73.0× 2.77e-4 6.55e-3 ✓ sig.
antigen processing and presentation
HLA-C, HLA-DQA1, HLA-DQB1, HLA-B
 GO:0019882 4 / 48 12.2× 3.24e-4 7.32e-3 ✓ sig.
monocyte differentiation
BMP4, RXRA, PPARG
 GO:0030224 3 / 20 21.9× 3.29e-4 7.37e-3 ✓ sig.
positive regulation of neuron differentiation
NGF, BMP4, GDPD5, PCP4, TCF4
 GO:0045666 5 / 87 8.4× 3.29e-4 7.38e-3 ✓ sig.
response to bacterium
CFB, TAB3, LRAT, CCL2, NAALADL2, SERPINE1
 GO:0009617 6 / 140 6.3× 4.07e-4 8.60e-3 ✓ sig.
positive regulation of lipoprotein transport
RXRA, PPARG
 GO:0140077 2 / 5 58.4× 4.59e-4 9.34e-3 ✓ sig.
cellular response to low-density lipoprotein particle stimulus
ABCA1, RXRA, PPARG
 GO:0071404 3 / 23 19.0× 5.03e-4 9.93e-3 ✓ sig.
negative regulation of chondrocyte differentiation
BMP4, EFEMP1, RARB
 GO:0032331 3 / 23 19.0× 5.03e-4 9.93e-3 ✓ sig.
kidney development
SERPINF1, BICC1, BMP4, PTCD2, RPGRIP1L, LRP2
 GO:0001822 6 / 146 6.0× 5.09e-4 1.00e-2 ✓ sig.
retinoic acid receptor signaling pathway
RARB, RXRA, PPARG
 GO:0048384 3 / 24 18.2× 5.72e-4 1.08e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Corneal ulcer Eye disease 0.072 7 8.97e-15 1.26e-13 ✓ sig.
Corneal ulcer Proliferative diabetic retinopathy 0.045 2 1.89e-4 5.35e-4 ✓ sig.
Corneal ulcer retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome 0.100 1 5.84e-4 1.16e-3 ✓ sig.
C syndrome Proliferative diabetic retinopathy 0.027 1 2.34e-3 3.24e-3 ✓ sig.
Eye disease retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome 0.011 1 6.10e-3 7.34e-3 ✓ sig.