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 309

6 diseases · 10 shared-gene connections
6 Diseases
256 Unique genes
0.134 Avg. similarity score
Graves disease Most-connected disease (5 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 ⇵
Graves disease 5 5 99
Thyroid disease 4 4 53
Hashimoto disease 3 3 27
Hyperthyroidism 3 3 53
Vitiligo 3 3 126
Charcot-Marie-Tooth disease, demyelinating, type 1J 2 2 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
BACH2 5 / 6 Graves disease, Hashimoto disease, Hyperthyroidism, Thyroid disease and 1 more
CTLA4 5 / 6 Graves disease, Hashimoto disease, Hyperthyroidism, Thyroid disease and 1 more
HLA-DQA1 5 / 6 Graves disease, Hashimoto disease, Hyperthyroidism, Thyroid disease and 1 more
ICOS 5 / 6 Graves disease, Hashimoto disease, Hyperthyroidism, Thyroid disease and 1 more
IL2RA 5 / 6 Graves disease, Hashimoto disease, Hyperthyroidism, Thyroid disease and 1 more
LPP 5 / 6 Graves disease, Hashimoto disease, Hyperthyroidism, Thyroid disease and 1 more
PTPN22 5 / 6 Graves disease, Hashimoto disease, Hyperthyroidism, Thyroid disease and 1 more
TG 5 / 6 Graves disease, Hashimoto disease, Hyperthyroidism, Thyroid disease and 1 more
FAM76B 4 / 6 Graves disease, Hashimoto disease, Thyroid disease, Vitiligo
HLA-DQB1 4 / 6 Graves disease, Hyperthyroidism, Thyroid disease, Vitiligo
HLA-DRB1 4 / 6 Graves disease, Hashimoto disease, Hyperthyroidism, Vitiligo
RNASET2 4 / 6 Graves disease, Hyperthyroidism, Thyroid disease, Vitiligo
STAT4 4 / 6 Graves disease, Hashimoto disease, Thyroid disease, Vitiligo
VAV3 4 / 6 Graves disease, Hashimoto disease, Hyperthyroidism, Thyroid disease
ARID5B 3 / 6 Graves disease, Thyroid disease, Vitiligo
ATXN2 3 / 6 Hashimoto disease, Thyroid disease, Vitiligo
C1QTNF6 3 / 6 Graves disease, Thyroid disease, Vitiligo
CCR6 3 / 6 Graves disease, Thyroid disease, Vitiligo
ITPR3 3 / 6 Charcot-Marie-Tooth disease, demyelinating, type 1J, Graves disease, Vitiligo
PDE8B 3 / 6 Hashimoto disease, Hyperthyroidism, Thyroid disease
PHTF1 3 / 6 Hyperthyroidism, Thyroid disease, Vitiligo
RSBN1 3 / 6 Hyperthyroidism, Thyroid disease, Vitiligo
SH2B3 3 / 6 Hashimoto disease, Thyroid disease, Vitiligo
TNF 3 / 6 Graves disease, Hyperthyroidism, Vitiligo
VEGFA 3 / 6 Graves disease, Hyperthyroidism, Thyroid disease
BTNL2 2 / 6 Graves disease, Vitiligo
C4A 2 / 6 Graves disease, Vitiligo
CAT 2 / 6 Hyperthyroidism, Vitiligo
CD69 2 / 6 Hashimoto disease, Thyroid disease
CEP43 2 / 6 Graves disease, Thyroid disease
CLNK 2 / 6 Thyroid disease, Vitiligo
FAM227B 2 / 6 Hyperthyroidism, Thyroid disease
FCRL3 2 / 6 Graves disease, Thyroid disease
IFIH1 2 / 6 Graves disease, Vitiligo
IFNG 2 / 6 Graves disease, Vitiligo
IL6 2 / 6 Graves disease, Hashimoto disease
IL6R 2 / 6 Graves disease, Hashimoto disease
MICOS10 2 / 6 Hyperthyroidism, Thyroid disease
MMEL1 2 / 6 Graves disease, Hashimoto disease
MUC22 2 / 6 Graves disease, Hyperthyroidism
NEK6 2 / 6 Thyroid disease, Vitiligo
NFIA 2 / 6 Hyperthyroidism, Thyroid disease
PDE10A 2 / 6 Hyperthyroidism, Thyroid disease
PRICKLE1 2 / 6 Graves disease, Hashimoto disease
PRSS36 2 / 6 Graves disease, Hashimoto disease
PTPRC 2 / 6 Hyperthyroidism, Vitiligo
RHOH 2 / 6 Graves disease, Vitiligo
SLC25A27 2 / 6 Graves disease, Hashimoto disease
SOD2 2 / 6 Hyperthyroidism, Vitiligo
TNFRSF8 2 / 6 Graves disease, Hashimoto disease
TNFSF8 2 / 6 Graves disease, Hashimoto disease
TPO 2 / 6 Graves disease, Thyroid disease
TSBP1 2 / 6 Graves disease, Hyperthyroidism
TSHR 2 / 6 Graves disease, Hyperthyroidism
UBASH3A 2 / 6 Graves disease, Vitiligo
VDR 2 / 6 Graves disease, Vitiligo
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 ⇵
Autoimmune thyroid disease
TSHR, CD40, CD40LG, CTLA4, HLA-B, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, IL10, IL2
 KEGG 24 / 54 20.9× 2.08e-26 4.42e-23 ✓ sig.
Allograft rejection
CD40, CD40LG, HLA-B, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, IFNG, IL10, IL2, IL4
 KEGG 21 / 39 25.3× 1.55e-25 2.96e-22 ✓ sig.
Inflammatory bowel disease
HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, IFNG, IL10, IL13, IL17A, IL1B, IL2, IL23R
 KEGG 25 / 66 17.8× 2.45e-25 4.51e-22 ✓ sig.
Type I diabetes mellitus
HLA-B, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, IFNG, IL1B, IL2, LTA, TNF, HLA-C
 KEGG 20 / 44 21.3× 1.99e-22 2.47e-19 ✓ sig.
Graft-versus-host disease
HLA-B, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, IFNG, IL1B, IL2, IL6, TNF, HLA-C
 KEGG 20 / 45 20.9× 3.51e-22 4.22e-19 ✓ sig.
Rheumatoid arthritis
CTLA4, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, ICAM1, IFNG, IL17A, IL1B, IL6, TGFB1
 KEGG 25 / 95 12.3× 7.54e-21 6.83e-18 ✓ sig.
Asthma
CD40, CD40LG, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, IL10, IL13, IL3, IL4, TNF
 KEGG 15 / 32 22.0× 2.32e-17 1.17e-14 ✓ sig.
Th17 cell differentiation
CD4, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, IFNG, IL17A, IL1B, IL2, IL23R, IL2RA
 KEGG 23 / 109 9.9× 6.11e-17 2.87e-14 ✓ sig.
Intestinal immune network for IgA production
CD40, CD40LG, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, ICOS, IL10, IL2, IL4, IL6
 KEGG 17 / 50 16.0× 1.20e-16 5.31e-14 ✓ sig.
Herpes simplex virus 1 infection
HLA-B, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, IFIH1, IFNG, IL1B, IL6, LTA, TNF
 KEGG 25 / 182 6.4× 9.61e-14 2.48e-11 ✓ sig.
Interleukin-4 and Interleukin-13 signaling
ICAM1, IL10, IL13, IL17A, IL1B, IL23R, IL4, IL6, IL6R, TGFB1, TNF, TP53
 Reactome 20 / 108 8.7× 9.85e-14 2.53e-11 ✓ sig.
Phosphorylation of CD3 and TCR zeta chains
CD4, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, PTPN22, HLA-DPB1, HLA-DRA, HLA-DRB5, PTPRC
 Reactome 11 / 22 23.5× 1.91e-13 4.60e-11 ✓ sig.
Hematopoietic cell lineage
CD4, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, IL1B, IL2RA, IL3, IL4, IL6, IL6R
 KEGG 19 / 100 8.9× 2.56e-13 6.08e-11 ✓ sig.
Leishmaniasis
HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, IFNG, IL10, IL1B, IL4, TGFB1, TNF, HLA-DPB1
 KEGG 17 / 78 10.2× 4.47e-13 1.03e-10 ✓ sig.
Translocation of ZAP-70 to Immunological synapse
CD4, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, PTPN22, HLA-DPB1, HLA-DRA, HLA-DRB5
 Reactome 10 / 19 24.7× 1.27e-12 2.72e-10 ✓ 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 ⇵
immune response
CCR6, CD4, CD40LG, CTLA4, FCRL3, HLA-B, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, ICAM1
 GO:0006955 43 / 543 5.8× 7.61e-21 1.39e-17 ✓ sig.
antigen processing and presentation
HLA-B, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, RAB5B, HLA-C, HLA-DPB1, HLA-DRA, HLA-DRB5, PSMB8
 GO:0019882 12 / 48 18.2× 1.52e-12 6.69e-10 ✓ sig.
positive regulation of T cell proliferation
BTNL2, CD4, CD40LG, HLA-DPA1, IL1B, IL2, IL23R, IL2RA, IL4, IL6, HLA-DPB1, PTPRC
 GO:0042102 13 / 67 14.2× 5.80e-12 2.25e-9 ✓ sig.
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II
HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, HLA-DPB1, HLA-DRA, HLA-DRB5
 GO:0002504 8 / 15 38.9× 6.59e-12 2.53e-9 ✓ sig.
peptide antigen assembly with MHC class II protein complex
HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, HLA-DPB1, HLA-DRA, HLA-DRB5
 GO:0002503 8 / 16 36.5× 1.30e-11 4.67e-9 ✓ sig.
positive regulation of T cell activation
CD4, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, HLA-DPB1, HLA-DRA, HLA-DRB5, CCL2, TNFSF11
 GO:0050870 11 / 45 17.8× 1.73e-11 6.01e-9 ✓ sig.
immune system process
C4A, C4B, CD4, CD40, CTLA4, HLA-B, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, IFIH1
 GO:0002376 41 / 943 3.2× 4.72e-11 1.46e-8 ✓ sig.
positive regulation of canonical NF-kappaB signal transduction
CD4, CD40, CD40LG, HLA-DRB1, IL1B, LTA, TGFB1, TNF, VEGFA, INSR, NEK6, CASP7
 GO:0043123 20 / 232 6.3× 7.04e-11 2.09e-8 ✓ sig.
response to lipopolysaccharide
CYP1A1, IL10, IL13, IL1B, IL23R, LTA, PTPN22, TNF, GPX1, SOD2, DIO2, FASLG
 GO:0032496 17 / 161 7.7× 8.22e-11 2.39e-8 ✓ sig.
positive regulation of transcription by RNA polymerase II
AAMDC, ADRB2, CD40, ESR2, IFNG, IL10, IL13, IL17A, IL1B, IL2, IL4, IL6
 GO:0045944 46 / 1,208 2.8× 2.23e-10 5.89e-8 ✓ sig.
positive regulation of B cell proliferation
CD40, FCRL3, IL13, IL2, IL4, VAV3, PRLR, PTPRC, TICAM1, TLR4
 GO:0030890 10 / 47 15.5× 6.48e-10 1.53e-7 ✓ sig.
positive regulation of smooth muscle cell proliferation
IL13, IL6, IL6R, TGFB1, TNF, ID2, CDH13, FOXP1, PIK3R1, TLR4
 GO:0048661 10 / 52 14.0× 1.86e-9 3.89e-7 ✓ sig.
positive regulation of MAPK cascade
ADRB2, CD4, CD40, FCRL3, HLA-DRB1, IL1B, IL6, IL6R, TGFB1, TNF, VEGFA, CARTPT
 GO:0043410 18 / 224 5.9× 2.01e-9 4.15e-7 ✓ sig.
positive regulation of osteoclast differentiation
IFNG, IL17A, IL23R, TNF, PPARGC1B, PPP3CA, TNFRSF11A, TNFSF11
 GO:0045672 8 / 28 20.9× 2.73e-9 5.43e-7 ✓ sig.
antigen processing and presentation of exogenous peptide antigen via MHC class II
HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, HLA-DPB1, HLA-DRA, HLA-DRB5
 GO:0019886 8 / 31 18.8× 6.68e-9 1.21e-6 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Graves disease Hashimoto disease 0.187 20 1.61e-39 7.04e-38 ✓ sig.
Hyperthyroidism Thyroid disease 0.216 19 4.45e-35 1.70e-33 ✓ sig.
Hashimoto disease Thyroid disease 0.227 15 2.15e-31 7.25e-30 ✓ sig.
Graves disease Thyroid disease 0.150 20 3.24e-31 1.09e-29 ✓ sig.
Graves disease Vitiligo 0.124 25 6.00e-31 1.99e-29 ✓ sig.
Thyroid disease Vitiligo 0.132 21 6.63e-31 2.19e-29 ✓ sig.
Graves disease Hyperthyroidism 0.125 17 3.47e-25 9.04e-24 ✓ sig.
Hashimoto disease Hyperthyroidism 0.157 11 3.32e-21 7.04e-20 ✓ sig.
Charcot-Marie-Tooth disease, demyelinating, type 1J Graves disease 0.010 1 6.43e-3 7.69e-3 ✓ sig.
Charcot-Marie-Tooth disease, demyelinating, type 1J Vitiligo 0.008 1 8.18e-3 9.49e-3 ✓ sig.