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 35

17 diseases · 47 shared-gene connections
17 Diseases
205 Unique genes
0.188 Avg. similarity score
monogenic diabetes Most-connected disease (10 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 ⇵
monogenic diabetes 10 10 10
Hyperinsulinism 8 8 42
Hypoglycemia 8 8 27
Maturity-onset diabetes of the young 8 8 13
Maturity-onset diabetes of the young (mody) 8 8 23
Permanent neonatal diabetes mellitus 8 8 14
Transient neonatal diabetes mellitus 8 8 9
Congenital hyperinsulinism 7 7 6
Neonatal diabetes mellitus 7 7 17
Hyperinsulinemic hypoglycemia 5 5 11
Hyperglycemia 4 4 52
Hyperinsulinism-hyperammonemia syndrome 4 4 1
Diabetic ketoacidosis 3 3 35
Fanconi-bickel syndrome 3 3 2
Abetalipoproteinemia 1 1 1
Carotid artery disease 1 1 55
glycogen storage disease I 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
GCK 11 / 17 Congenital hyperinsulinism, Hyperglycemia, Hyperinsulinemic hypoglycemia, Hyperinsulinism and 7 more
ABCC8 10 / 17 Congenital hyperinsulinism, Hyperinsulinemic hypoglycemia, Hyperinsulinism, Hypoglycemia and 6 more
INS 10 / 17 Diabetic ketoacidosis, Hyperglycemia, Hyperinsulinism, Hypoglycemia and 6 more
KCNJ11 10 / 17 Congenital hyperinsulinism, Hyperinsulinemic hypoglycemia, Hyperinsulinism, Hypoglycemia and 6 more
HNF1A 6 / 17 Hyperglycemia, Hyperinsulinism, Hypoglycemia, Maturity-onset diabetes of the young and 2 more
HNF4A 6 / 17 Congenital hyperinsulinism, Hyperinsulinism, Hypoglycemia, Maturity-onset diabetes of the young and 2 more
INS-IGF2 6 / 17 Diabetic ketoacidosis, Hyperglycemia, Hypoglycemia, Maturity-onset diabetes of the young (mody) and 2 more
PDX1 6 / 17 Hyperglycemia, Maturity-onset diabetes of the young, Maturity-onset diabetes of the young (mody), monogenic diabetes and 2 more
GLUD1 5 / 17 Congenital hyperinsulinism, Hyperinsulinemic hypoglycemia, Hyperinsulinism, Hyperinsulinism-hyperammonemia syndrome and 1 more
NEUROD1 5 / 17 Hyperglycemia, Maturity-onset diabetes of the young, Maturity-onset diabetes of the young (mody), monogenic diabetes and 1 more
SLC2A2 5 / 17 Diabetic ketoacidosis, Fanconi-bickel syndrome, Neonatal diabetes mellitus, Permanent neonatal diabetes mellitus and 1 more
PAX4 4 / 17 Diabetic ketoacidosis, Hyperglycemia, Maturity-onset diabetes of the young, Maturity-onset diabetes of the young (mody)
CCL2 3 / 17 Carotid artery disease, Hyperglycemia, Hyperinsulinism
CD163 3 / 17 Carotid artery disease, Hyperglycemia, Hyperinsulinism
GATA4 3 / 17 Neonatal diabetes mellitus, Permanent neonatal diabetes mellitus, Transient neonatal diabetes mellitus
HADH 3 / 17 Congenital hyperinsulinism, Hyperinsulinemic hypoglycemia, Hyperinsulinism
HNF1B 3 / 17 Maturity-onset diabetes of the young (mody), Permanent neonatal diabetes mellitus, Transient neonatal diabetes mellitus
INSR 3 / 17 Hyperglycemia, Hyperinsulinemic hypoglycemia, Hyperinsulinism
KLF11 3 / 17 Hyperglycemia, Maturity-onset diabetes of the young, Maturity-onset diabetes of the young (mody)
AGT 2 / 17 Carotid artery disease, Hyperinsulinism
APPL1 2 / 17 Maturity-onset diabetes of the young, Maturity-onset diabetes of the young (mody)
BLK 2 / 17 Maturity-onset diabetes of the young, Maturity-onset diabetes of the young (mody)
CD40 2 / 17 Hyperglycemia, Hyperinsulinism
CEL 2 / 17 Maturity-onset diabetes of the young, Maturity-onset diabetes of the young (mody)
COL3A1 2 / 17 Hyperglycemia, Hyperinsulinism
CYP2C9 2 / 17 Hyperglycemia, Hypoglycemia
FBN1 2 / 17 Hyperglycemia, Hyperinsulinism
FCGR3B 2 / 17 Hyperglycemia, Hyperinsulinism
G6PC1 2 / 17 glycogen storage disease I, Hypoglycemia
GCG 2 / 17 Hyperglycemia, Hyperinsulinism
GPX1 2 / 17 Hyperglycemia, Hyperinsulinism
HMOX1 2 / 17 Carotid artery disease, Hyperinsulinism
IL6 2 / 17 Hyperglycemia, Hyperinsulinism
ITGAM 2 / 17 Hyperglycemia, Hyperinsulinism
LEP 2 / 17 Hyperglycemia, Hyperinsulinism
LEPR 2 / 17 Hyperglycemia, Hyperinsulinism
LTA 2 / 17 Carotid artery disease, Hyperinsulinism
MNX1 2 / 17 Neonatal diabetes mellitus, Permanent neonatal diabetes mellitus
MTTP 2 / 17 Abetalipoproteinemia, Hyperinsulinism
NOS3 2 / 17 Hyperglycemia, Hyperinsulinism
PTF1A 2 / 17 Maturity-onset diabetes of the young (mody), Permanent neonatal diabetes mellitus
RFX6 2 / 17 Maturity-onset diabetes of the young (mody), monogenic diabetes
SHLD2 2 / 17 Hyperinsulinemic hypoglycemia, Hyperinsulinism
SLC16A1 2 / 17 Hyperinsulinemic hypoglycemia, Hyperinsulinism
SOD2 2 / 17 Carotid artery disease, Hypoglycemia
TNF 2 / 17 Hyperinsulinism, Hypoglycemia
UCP2 2 / 17 Carotid artery disease, Hyperinsulinism
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 ⇵
Maturity onset diabetes of the young
GCK, HNF4A, HNF1B, INS, MNX1, NEUROG3, PDX1, SLC2A2, PAX4, HNF1A, NEUROD1, RFX6
 KEGG 14 / 26 31.5× 9.20e-19 6.24e-16 ✓ sig.
Insulin resistance
AGT, INS, SLC2A2, STAT3, IL6, INSR, IRS2, NOS3, PRKCB, IRS1, PTPN1, PTPRF
 KEGG 17 / 109 9.1× 3.74e-12 7.27e-10 ✓ sig.
Type II diabetes mellitus
KCNJ11, ABCC8, GCK, INS, PDX1, SLC2A2, ADIPOQ, INSR, IRS2, IRS1, TNF, CACNA1C
 KEGG 12 / 47 15.0× 1.37e-11 2.38e-9 ✓ sig.
Interleukin-4 and Interleukin-13 signaling
CCL2, FASLG, HMOX1, MMP1, MMP2, MMP9, TP53, STAT3, IL13, CCL11, IL6, ITGAM
 Reactome 15 / 108 8.1× 3.95e-10 4.92e-8 ✓ sig.
Lipid and atherosclerosis
CCL2, CD14, FASLG, MMP1, MMP9, PPARG, SOD2, TLR4, TP53, STAT3, AGER, CD40
 KEGG 19 / 216 5.2× 4.84e-9 4.61e-7 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
AGT, AGTR1, CCL2, MMP2, STAT3, AGER, COL3A1, IL6, NOS3, PRKCB, TNF, AKT2
 KEGG 13 / 101 7.5× 1.56e-8 1.29e-6 ✓ sig.
Adipocytokine signaling pathway
STAT3, ADIPOQ, IRS2, LEP, LEPR, IRS1, TNF, AKT2, G6PC1, PPARA, APPL1
 KEGG 11 / 70 9.2× 2.46e-8 1.93e-6 ✓ sig.
Hormone signaling
AGT, AGTR1, GNB3, PRL, INS, STAT3, ADIPOQ, GCG, INSR, IRS2, LEP, LEPR
 KEGG 17 / 219 4.5× 2.01e-7 1.20e-5 ✓ sig.
Longevity regulating pathway
PPARG, SOD2, TP53, INS, ADIPOQ, INSR, IRS2, IRS1, AKT2, APPL1, SIRT1
 KEGG 11 / 90 7.2× 3.51e-7 1.97e-5 ✓ sig.
IRS activation
INS, INSR, IRS2, IRS1
 Reactome 4 / 5 46.9× 4.07e-7 2.24e-5 ✓ sig.
Non-alcoholic fatty liver disease
FASLG, PPARG, INS, ADIPOQ, IL6, INSR, IRS2, LEP, LEPR, IRS1, TNF, AKT2
 KEGG 14 / 157 5.2× 4.68e-7 2.53e-5 ✓ sig.
AMPK signaling pathway
PPARG, HNF4A, INS, ADIPOQ, INSR, IRS2, LEP, LEPR, IRS1, AKT2, G6PC1, SIRT1
 KEGG 12 / 122 5.8× 1.11e-6 5.36e-5 ✓ sig.
Diabetic cardiomyopathy
AGT, AGTR1, MMP2, MMP9, INS, AGER, COL3A1, INSR, NOS3, PRKCB, SP1, IRS1
 KEGG 15 / 205 4.3× 2.27e-6 9.79e-5 ✓ sig.
HIF-1 signaling pathway
HMOX1, TLR4, INS, STAT3, LDHA, IL6, INSR, NOS3, PRKCB, TF, AKT2
 KEGG 11 / 110 5.9× 2.67e-6 1.13e-4 ✓ sig.
Pathways in cancer
AGT, AGTR1, FASLG, GNB3, GSTP1, HMOX1, MMP1, MMP2, MMP9, PPARG, TP53, STAT3
 KEGG 25 / 533 2.7× 4.26e-6 1.66e-4 ✓ 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 ⇵
glucose homeostasis
PPARG, GCK, HNF4A, INS, PDX1, STAT3, ADIPOQ, FBN1, GCG, HNF1A, IL6, INSR
 GO:0042593 19 / 134 12.9× 4.64e-16 3.87e-13 ✓ sig.
regulation of insulin secretion
KCNJ11, GCK, HADH, HNF4A, GCG, IL6, LEP, NEUROD1, SLC16A1, TNF, IL1B, RFX6
 GO:0050796 12 / 46 23.8× 6.17e-14 3.52e-11 ✓ sig.
glucose metabolic process
KCNJ11, GCK, INS, PDX1, ADIPOQ, FBN1, IRS2, LEP, TNF, AKT2, IGF2, ONECUT1
 GO:0006006 12 / 66 16.6× 6.44e-12 2.48e-9 ✓ sig.
response to xenobiotic stimulus
KCNJ11, ABCC8, LTA, MMP2, SOD2, TP53, HADH, GATA4, PDX1, SCNN1B, SNCA, ADIPOQ
 GO:0009410 19 / 248 7.0× 3.53e-11 1.12e-8 ✓ sig.
endocrine pancreas development
HNF1B, MNX1, PDX1, IL6, NEUROD1, RFX6, NKX2-2, ONECUT1
 GO:0031018 8 / 22 33.1× 5.13e-11 1.58e-8 ✓ sig.
response to nutrient levels
GSTP1, PPARG, PRL, SOD2, PDX1, ADIPOQ, CD40, LEP, SOD1, PTPN1, TNF, G6PC1
 GO:0031667 12 / 79 13.8× 5.92e-11 1.79e-8 ✓ sig.
cellular response to insulin stimulus
GSTP1, PPARG, UCP2, GCK, ADIPOQ, INSR, IRS2, LEP, SP1, IRS1, PTPN1, AKT2
 GO:0032869 13 / 102 11.6× 9.04e-11 2.62e-8 ✓ sig.
positive regulation of D-glucose import
INS, ADIPOQ, INSR, IRS2, NFE2L2, TERT, IRS1, AKT2, APPL1
 GO:0046326 9 / 38 21.6× 2.39e-10 6.25e-8 ✓ sig.
positive regulation of glycogen biosynthetic process
GCK, INS, INSR, IRS2, IRS1, AKT2, IGF2
 GO:0045725 7 / 17 37.5× 3.06e-10 7.79e-8 ✓ sig.
type B pancreatic cell differentiation
PDX1, PAX4, RFX6, GATA6, NKX2-2, ONECUT1
 GO:0003309 6 / 10 54.7× 3.28e-10 8.30e-8 ✓ sig.
response to oxidative stress
APOE, HMOX1, MMP2, SOD2, TP53, GPX1, NFE2L2, NQO1, PRDX4, PTGS2, SOD1, LIAS
 GO:0006979 14 / 146 8.7× 7.92e-10 1.82e-7 ✓ sig.
positive regulation of DNA-templated transcription
AGT, APOE, PPARG, TP53, HNF4A, GATA4, HNF1B, NEUROG3, PDX1, PTF1A, STAT3, CASZ1
 GO:0045893 30 / 778 3.5× 1.99e-9 4.11e-7 ✓ sig.
positive regulation of angiogenesis
HMOX1, GATA4, STAT3, ADM, CCL11, CD40, NFE2L2, NOS3, PRKCB, SP1, TERT, IL1B
 GO:0045766 14 / 159 8.0× 2.44e-9 4.92e-7 ✓ sig.
response to lipopolysaccharide
ABCC8, FASLG, LTA, SOD2, TLR4, IL13, SNCA, CNR2, GPX1, NOS3, NQO1, LIAS
 GO:0032496 14 / 161 7.9× 2.87e-9 5.68e-7 ✓ sig.
response to glucose
UCP2, GCK, HNF4A, HNF1B, PDX1, ADIPOQ, GPX1, IRS2, NEUROD1, NKX2-2
 GO:0009749 10 / 68 13.4× 3.39e-9 6.60e-7 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Maturity-onset diabetes of the young Maturity-onset diabetes of the young (mody) 0.542 13 2.62e-39 1.13e-37 ✓ sig.
Hyperglycemia Hyperinsulinism 0.218 17 1.24e-32 4.36e-31 ✓ sig.
Maturity-onset diabetes of the young (mody) monogenic diabetes 0.360 9 6.10e-26 1.64e-24 ✓ sig.
Neonatal diabetes mellitus Permanent neonatal diabetes mellitus 0.391 9 3.63e-25 9.42e-24 ✓ sig.
Maturity-onset diabetes of the young monogenic diabetes 0.500 8 7.40e-25 1.90e-23 ✓ sig.
Maturity-onset diabetes of the young (mody) Permanent neonatal diabetes mellitus 0.310 9 1.22e-23 2.91e-22 ✓ sig.
Permanent neonatal diabetes mellitus Transient neonatal diabetes mellitus 0.412 7 3.04e-21 6.46e-20 ✓ sig.
Hyperinsulinemic hypoglycemia Hyperinsulinism 0.174 8 2.47e-19 4.79e-18 ✓ sig.
monogenic diabetes Permanent neonatal diabetes mellitus 0.316 6 3.40e-17 5.93e-16 ✓ sig.
Neonatal diabetes mellitus Transient neonatal diabetes mellitus 0.286 6 5.61e-17 9.66e-16 ✓ sig.
Maturity-onset diabetes of the young Permanent neonatal diabetes mellitus 0.273 6 2.78e-16 4.58e-15 ✓ sig.
Congenital hyperinsulinism Hyperinsulinism 0.140 6 2.84e-16 4.66e-15 ✓ sig.
Congenital hyperinsulinism Hyperinsulinemic hypoglycemia 0.385 5 3.84e-16 6.27e-15 ✓ sig.
Hyperinsulinism Hypoglycemia 0.129 8 3.23e-15 4.92e-14 ✓ sig.
Hypoglycemia monogenic diabetes 0.188 6 3.35e-15 5.10e-14 ✓ sig.
Hyperglycemia Maturity-onset diabetes of the young (mody) 0.118 8 4.54e-15 6.88e-14 ✓ sig.
Hypoglycemia Maturity-onset diabetes of the young (mody) 0.159 7 5.26e-15 7.95e-14 ✓ sig.
Hyperglycemia Maturity-onset diabetes of the young 0.119 7 5.56e-15 8.40e-14 ✓ sig.
Hypoglycemia Maturity-onset diabetes of the young 0.171 6 2.72e-14 3.91e-13 ✓ sig.
Hyperinsulinism monogenic diabetes 0.128 6 5.91e-14 8.25e-13 ✓ sig.
Maturity-onset diabetes of the young (mody) Neonatal diabetes mellitus 0.171 6 6.69e-14 9.27e-13 ✓ sig.
Congenital hyperinsulinism Hypoglycemia 0.172 5 6.71e-14 9.30e-13 ✓ sig.
monogenic diabetes Neonatal diabetes mellitus 0.217 5 2.16e-13 2.91e-12 ✓ sig.
Maturity-onset diabetes of the young (mody) Transient neonatal diabetes mellitus 0.179 5 5.86e-13 7.63e-12 ✓ sig.
Maturity-onset diabetes of the young Neonatal diabetes mellitus 0.192 5 1.10e-12 1.40e-11 ✓ sig.
Congenital hyperinsulinism monogenic diabetes 0.308 4 1.34e-12 1.70e-11 ✓ sig.
Congenital hyperinsulinism Maturity-onset diabetes of the young 0.250 4 4.58e-12 5.48e-11 ✓ sig.
monogenic diabetes Transient neonatal diabetes mellitus 0.250 4 1.13e-11 1.31e-10 ✓ sig.
Hypoglycemia Permanent neonatal diabetes mellitus 0.135 5 2.22e-11 2.49e-10 ✓ sig.
Maturity-onset diabetes of the young Transient neonatal diabetes mellitus 0.211 4 3.84e-11 4.20e-10 ✓ sig.
Hyperglycemia monogenic diabetes 0.086 5 8.97e-11 9.52e-10 ✓ sig.
Congenital hyperinsulinism Transient neonatal diabetes mellitus 0.231 3 2.76e-9 2.52e-8 ✓ sig.
Carotid artery disease Hyperinsulinism 0.065 6 7.45e-9 6.55e-8 ✓ sig.
Hyperinsulinemic hypoglycemia Transient neonatal diabetes mellitus 0.167 3 2.27e-8 1.87e-7 ✓ sig.
Hyperinsulinemic hypoglycemia monogenic diabetes 0.158 3 3.25e-8 2.59e-7 ✓ sig.
Diabetic ketoacidosis Permanent neonatal diabetes mellitus 0.064 3 3.85e-6 2.15e-5 ✓ sig.
Diabetic ketoacidosis Neonatal diabetes mellitus 0.060 3 7.16e-6 3.82e-5 ✓ sig.
Diabetic ketoacidosis Maturity-onset diabetes of the young (mody) 0.054 3 1.85e-5 9.31e-5 ✓ sig.
Congenital hyperinsulinism Hyperinsulinism-hyperammonemia syndrome 0.143 1 3.90e-4 8.52e-4 ✓ sig.
Hyperinsulinemic hypoglycemia Hyperinsulinism-hyperammonemia syndrome 0.083 1 7.14e-4 1.31e-3 ✓ sig.
Fanconi-bickel syndrome Transient neonatal diabetes mellitus 0.091 1 1.17e-3 1.88e-3 ✓ sig.
Hyperinsulinism-hyperammonemia syndrome Hypoglycemia 0.036 1 1.75e-3 2.59e-3 ✓ sig.
glycogen storage disease I Hypoglycemia 0.036 1 1.75e-3 2.59e-3 ✓ sig.
Fanconi-bickel syndrome Permanent neonatal diabetes mellitus 0.063 1 1.82e-3 2.66e-3 ✓ sig.
Fanconi-bickel syndrome Neonatal diabetes mellitus 0.053 1 2.21e-3 3.10e-3 ✓ sig.
Hyperinsulinism Hyperinsulinism-hyperammonemia syndrome 0.023 1 2.73e-3 3.65e-3 ✓ sig.
Abetalipoproteinemia Hyperinsulinism 0.023 1 2.73e-3 3.65e-3 ✓ sig.