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 226

7 diseases · 7 shared-gene connections
7 Diseases
692 Unique genes
0.067 Avg. similarity score
Cholelithiasis Most-connected disease (4 links)
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Disease Searched: hyperphenylalaninemia due to DNAJC12 deficiency 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 ⇵
Cholelithiasis 4 4 139
Liver cirrhosis 3 3 264
Liver disease 2 2 157
Nonalcoholic fatty liver disease 2 2 316
Hyperbiliverdinemia 1 1 1
Peliosis hepatis 1 1 1
hyperphenylalaninemia due to DNAJC12 deficiency 1 1 1

Top shared genes (genes linked to 2+ member diseases ‐ top 100 shown, download for all)

Gene ⇵ Member diseases ⇵ Linked diseases
ABCB4 4 / 7 Cholelithiasis, Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
CYP1A2 4 / 7 Cholelithiasis, Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
SERPINA1 4 / 7 Cholelithiasis, Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
TNF 4 / 7 Cholelithiasis, Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
ABCB11 3 / 7 Cholelithiasis, Liver cirrhosis, Liver disease
ABCC2 3 / 7 Cholelithiasis, Liver cirrhosis, Nonalcoholic fatty liver disease
ACTA2 3 / 7 Cholelithiasis, Liver cirrhosis, Liver disease
AHR 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
ALDH2 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
APOC1 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
APOE 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
CAT 3 / 7 Cholelithiasis, Liver cirrhosis, Nonalcoholic fatty liver disease
COL3A1 3 / 7 Cholelithiasis, Liver cirrhosis, Liver disease
CYP2E1 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
GSTT1 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
HFE 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
IFNL4 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
IL6 3 / 7 Cholelithiasis, Liver cirrhosis, Nonalcoholic fatty liver disease
KHDRBS3 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
KLHL8 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
MTARC1 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
MTHFR 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
NFE2L2 3 / 7 Cholelithiasis, Liver cirrhosis, Nonalcoholic fatty liver disease
NOS2 3 / 7 Cholelithiasis, Liver cirrhosis, Liver disease
NQO1 3 / 7 Cholelithiasis, Liver disease, Nonalcoholic fatty liver disease
NR1H4 3 / 7 Cholelithiasis, Liver disease, Nonalcoholic fatty liver disease
PNPLA3 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
SERPINA2 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
SERPINE1 3 / 7 Cholelithiasis, Liver cirrhosis, Liver disease
ST8SIA1 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
TGFB1 3 / 7 Cholelithiasis, Liver cirrhosis, Nonalcoholic fatty liver disease
TM6SF2 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
TRIB1 3 / 7 Liver cirrhosis, Liver disease, Nonalcoholic fatty liver disease
ACE 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
AGT 2 / 7 Cholelithiasis, Liver cirrhosis
AKNA 2 / 7 Liver disease, Nonalcoholic fatty liver disease
ALAD 2 / 7 Liver cirrhosis, Liver disease
ALB 2 / 7 Cholelithiasis, Liver cirrhosis
ALDH1A1 2 / 7 Liver disease, Nonalcoholic fatty liver disease
ALDH1B1 2 / 7 Cholelithiasis, Nonalcoholic fatty liver disease
ATP7B 2 / 7 Liver cirrhosis, Liver disease
BCL2 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
BLVRA 2 / 7 Cholelithiasis, Hyperbiliverdinemia
CACNA2D1 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
CCL2 2 / 7 Liver cirrhosis, Liver disease
CCN2 2 / 7 Cholelithiasis, Liver cirrhosis
CCR2 2 / 7 Liver disease, Nonalcoholic fatty liver disease
CD14 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
CD3D 2 / 7 Liver cirrhosis, Liver disease
CDH2 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
CHST2 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
CNR1 2 / 7 Cholelithiasis, Liver cirrhosis
CNR2 2 / 7 Cholelithiasis, Liver cirrhosis
CNTN5 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
COL13A1 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
COL1A1 2 / 7 Cholelithiasis, Liver cirrhosis
COMMD1 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
CRACR2A 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
CYGB 2 / 7 Cholelithiasis, Liver cirrhosis
CYP27A1 2 / 7 Cholelithiasis, Liver cirrhosis
CYP7A1 2 / 7 Cholelithiasis, Liver disease
CYP7B1 2 / 7 Cholelithiasis, Liver disease
DCLK1 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
DDX60L 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
DGAT2 2 / 7 Cholelithiasis, Nonalcoholic fatty liver disease
DNAJC12 2 / 7 Cholelithiasis, hyperphenylalaninemia due to DNAJC12 deficiency
EHBP1L1 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
ERLIN1 2 / 7 Liver disease, Nonalcoholic fatty liver disease
F2 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
F2RL3 2 / 7 Cholelithiasis, Peliosis hepatis
FARP1 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
FDFT1 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
FOCAD 2 / 7 Liver cirrhosis, Liver disease
GC 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
GCKR 2 / 7 Liver disease, Nonalcoholic fatty liver disease
GGT1 2 / 7 Liver disease, Nonalcoholic fatty liver disease
GPAM 2 / 7 Liver disease, Nonalcoholic fatty liver disease
GPT 2 / 7 Liver disease, Nonalcoholic fatty liver disease
GSTM1 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
GSTP1 2 / 7 Liver disease, Nonalcoholic fatty liver disease
HERPUD2 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
HKDC1 2 / 7 Liver cirrhosis, Liver disease
HLA-DQA1 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
HLA-DRB1 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
HS3ST1 2 / 7 Liver disease, Nonalcoholic fatty liver disease
HSD17B13 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
ICAM1 2 / 7 Cholelithiasis, Liver cirrhosis
IGF1 2 / 7 Cholelithiasis, Liver cirrhosis
IL1B 2 / 7 Cholelithiasis, Nonalcoholic fatty liver disease
INS 2 / 7 Liver disease, Nonalcoholic fatty liver disease
JCAD 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
KEAP1 2 / 7 Cholelithiasis, Liver cirrhosis
LCP1 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
LDLR 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
LEP 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
MACROD2 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
MAPK14 2 / 7 Cholelithiasis, Liver cirrhosis
MBL2 2 / 7 Liver cirrhosis, Liver disease
MBOAT7 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver disease
MLXIPL 2 / 7 Liver cirrhosis, Nonalcoholic fatty liver 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 ⇵
AGE-RAGE signaling pathway in diabetic complications
AGT, CXCL8, EGR1, ICAM1, IL6, MAPK13, MAPK14, RELA, SERPINE1, TNF, VCAM1, COL1A1
 KEGG 44 / 101 7.6× 3.06e-28 6.94e-25 ✓ sig.
Lipid and atherosclerosis
CXCL2, CXCL8, CYP2B6, ICAM1, IL6, LY96, MAPK13, MAPK14, NFE2L2, RELA, TLR2, TNF
 KEGG 58 / 216 4.7× 5.93e-24 8.67e-21 ✓ sig.
Interleukin-4 and Interleukin-13 signaling
CXCL8, ICAM1, IL6, NOS2, POMC, TNF, VCAM1, FOS, IL1B, MMP2, MMP9, TGFB1
 Reactome 41 / 108 6.6× 1.36e-23 1.82e-20 ✓ sig.
Chagas disease
CXCL8, IL6, MAPK13, MAPK14, NOS2, RELA, SERPINE1, TLR2, TNF, FOS, IL1B, JUN
 KEGG 39 / 103 6.6× 1.89e-22 2.08e-19 ✓ sig.
Leishmaniasis
MAPK13, MAPK14, NOS2, RELA, TLR2, TNF, FOS, IL1B, JUN, MAP3K7, MAPK1, MAPK3
 KEGG 34 / 78 7.6× 4.28e-22 4.54e-19 ✓ sig.
Toxoplasmosis
LY96, MAPK13, MAPK14, NOS2, RELA, TLR2, TNF, MAP3K7, MAPK1, MAPK3, MAPK8, MAPK9
 KEGG 40 / 112 6.2× 6.89e-22 6.96e-19 ✓ sig.
Interleukin-10 signaling
CXCL2, CXCL8, ICAM1, IL6, TNF, IL1B, TIMP1, CCL2, CCL5, IL10, PTGS2, TNFRSF1B
 Reactome 27 / 47 10.0× 6.86e-22 6.96e-19 ✓ sig.
Alcoholic liver disease
ALDH1B1, CXCL2, CXCL8, IL6, LY96, MAPK13, MAPK14, PRKAG2, RELA, TNF, IL1B, MAP3K7
 KEGG 44 / 144 5.3× 7.47e-21 6.06e-18 ✓ sig.
Pathways in cancer
ADCY9, AGT, CXCL8, F2RL3, IGF1, IL6, NFE2L2, NOS2, NQO1, RELA, FOS, JUN
 KEGG 88 / 533 2.9× 6.78e-20 4.86e-17 ✓ sig.
Fluid shear stress and atherosclerosis
ICAM1, MAPK13, MAPK14, NFE2L2, NQO1, RELA, TNF, VCAM1, FOS, IL1B, JUN, KEAP1
 KEGG 41 / 141 5.0× 1.25e-18 7.67e-16 ✓ sig.
Toll-like receptor signaling pathway
CXCL8, IL6, LY96, MAPK13, MAPK14, RELA, TLR2, TNF, FOS, IL1B, JUN, MAP3K7
 KEGG 36 / 109 5.7× 1.59e-18 9.64e-16 ✓ sig.
Th17 cell differentiation
IL6, MAPK13, MAPK14, RELA, FOS, IL1B, JUN, MAPK1, MAPK3, MAPK8, MAPK9, TGFB1
 KEGG 34 / 109 5.4× 1.07e-16 4.68e-14 ✓ sig.
Relaxin signaling pathway
ADCY9, MAPK13, MAPK14, NOS2, RELA, ACTA2, COL1A1, COL3A1, FOS, JUN, MAPK1, MAPK3
 KEGG 37 / 130 4.9× 1.36e-16 5.81e-14 ✓ sig.
Influenza A
CXCL8, ICAM1, IL6, RELA, TNF, IL1B, MAPK1, MAPK3, MYD88, TLR4, HLA-DPB1, HLA-DQB1
 KEGG 42 / 173 4.2× 6.37e-16 2.48e-13 ✓ sig.
Inflammatory bowel disease
IL6, RELA, TLR2, TNF, IL1B, JUN, TGFB1, TLR4, MAF, HLA-DPB1, HLA-DQB1, HLA-DPA1
 KEGG 26 / 66 6.8× 6.97e-16 2.63e-13 ✓ 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 ⇵
cellular response to lipopolysaccharide
CXCL8, IL6, LY96, MAPK14, NOS2, NR1H3, NR1H4, RELA, SERPINE1, TNF, CD68, HMGB1
 GO:0071222 41 / 187 5.9× 1.46e-20 2.49e-17 ✓ sig.
response to lipopolysaccharide
BLVRA, CNR2, LY96, MAPK14, NOS2, NQO1, RELA, TNF, VCAM1, FOS, IL1B, MAPK1
 GO:0032496 38 / 161 6.4× 2.45e-20 4.05e-17 ✓ sig.
immune response
CCL7, CNR2, CXCL2, CXCL8, ICAM1, IL6, TLR2, TNF, HMGB1, IL1B, MAP3K7, TLR4
 GO:0006955 70 / 543 3.5× 4.67e-20 7.33e-17 ✓ sig.
positive regulation of MAPK cascade
IGF1, IL6, TNF, HMGB1, IL1B, MAP3K7, TGFB1, CDH2, JCAD, ADRA1A, CTNNB1, DRD4
 GO:0043410 42 / 224 5.1× 2.41e-18 2.95e-15 ✓ sig.
positive regulation of gene expression
CXCL8, EGR1, ID4, IGF1, IL6, MAPK14, NFE2L2, NR1H2, RDX, RELA, TLR2, TNF
 GO:0010628 63 / 504 3.4× 1.82e-17 1.94e-14 ✓ sig.
response to xenobiotic stimulus
CAT, NFE2L2, RELA, TNF, COL1A1, FOS, JUN, MMP2, TGFB1, ADRA1A, AHR, ALAD
 GO:0009410 42 / 248 4.6× 1.14e-16 1.07e-13 ✓ sig.
inflammatory response
BLVRA, CCL7, CNR2, CXCL2, CXCL8, IL6, LY96, NFE2L2, NOS2, NR1H4, RELA, TLR2
 GO:0006954 59 / 467 3.4× 1.23e-16 1.14e-13 ✓ sig.
lipid metabolic process
ABCB4, BCAT1, CYP1A2, CYP27A1, CYP2B6, CYP7A1, CYP7B1, CYP8B1, DGAT2, HACL1, HAO2, HSD3B7
 GO:0006629 83 / 840 2.7× 2.16e-16 1.95e-13 ✓ sig.
response to hypoxia
CAT, EGR1, NOS2, TNF, VCAM1, CYGB, MAP3K7, MMP2, TGFB1, ALAD, ARNT, CYBA
 GO:0001666 35 / 176 5.4× 2.52e-16 2.24e-13 ✓ sig.
positive regulation of miRNA transcription
AGT, EGR1, IL6, NR1H2, RELA, TNF, WT1, FOS, JUN, TGFB1, FGF2, FOXO3
 GO:1902895 21 / 56 10.1× 2.57e-16 2.28e-13 ✓ sig.
positive regulation of interleukin-6 production
IL6, MAPK13, NOS2, RELA, TLR2, TNF, HMGB1, IL1B, MYD88, TGFB1, TLR4, CYBA
 GO:0032755 25 / 103 6.6× 3.96e-14 2.34e-11 ✓ sig.
positive regulation of cell migration
CCL7, IGF1, SNAI1, VIL1, COL1A1, IL1B, MMP2, TGFB1, SEMA7A, RNF7, ATM, CCL2
 GO:0030335 41 / 292 3.8× 1.94e-13 1.01e-10 ✓ sig.
positive regulation of transcription by RNA polymerase II
EGR1, HJV, ID4, IGF1, IL6, MAML3, MAPK14, NFE2L2, NR1H2, NR1H3, NR1H4, POMC
 GO:0045944 97 / 1,208 2.2× 2.99e-13 1.51e-10 ✓ sig.
response to ethanol
CAT, CYP7A1, RELA, SLC10A1, TNF, VCAM1, CD68, FOS, MYD88, TGFB1, ALAD, FGF19
 GO:0045471 24 / 110 5.9× 1.57e-12 6.99e-10 ✓ sig.
positive regulation of cell population proliferation
ID4, IGF1, IL6, RELA, IL1B, TGFB1, TIMP1, MLXIPL, BAMBI, CTNNB1, F2, F2R
 GO:0008284 56 / 532 2.8× 1.81e-12 7.95e-10 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Liver cirrhosis Nonalcoholic fatty liver disease 0.155 78 9.78e-70 6.94e-68 ✓ sig.
Liver disease Nonalcoholic fatty liver disease 0.107 46 1.37e-40 5.83e-39 ✓ sig.
Liver cirrhosis Liver disease 0.093 36 1.53e-30 4.73e-29 ✓ sig.
Cholelithiasis Liver cirrhosis 0.092 34 6.62e-30 2.02e-28 ✓ sig.
Cholelithiasis Hyperbiliverdinemia 0.007 1 9.03e-3 1.03e-2 ✓ sig.
Cholelithiasis hyperphenylalaninemia due to DNAJC12 deficiency 0.007 1 9.03e-3 1.03e-2 ✓ sig.
Cholelithiasis Peliosis hepatis 0.007 1 9.03e-3 1.03e-2 ✓ sig.