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 49

16 diseases · 35 shared-gene connections
16 Diseases
106 Unique genes
0.161 Avg. similarity score
Cardiofaciocutaneous syndrome 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 ⇵
Cardiofaciocutaneous syndrome 10 10 12
Costello syndrome 9 9 13
Non-immune hydrops fetalis 8 8 45
Noonan syndrome 7 7 37
noonan syndrome with multiple lentigines 7 7 5
Congenital malformation syndromes associated with short stature 5 5 6
Leopard syndrome 5 5 11
Noonan syndrome-like disorder with loose anagen hair 4 4 2
Blepharoptosis 3 3 19
Corticobasal degeneration 3 3 7
Myelomonocytic leukemia 3 3 10
Osteochondroma 2 2 1
Congenital malrotation of intestine 1 1 1
Desmosterolosis 1 1 1
arrhythmogenic cardiomyopathy with variable ectodermal abnormalities 1 1 1
sulfite oxidase deficiency due to molybdenum cofactor deficiency type B2 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
PTPN11 10 / 16 Blepharoptosis, Cardiofaciocutaneous syndrome, Congenital malformation syndromes associated with short stature, Costello syndrome and 6 more
BRAF 6 / 16 Cardiofaciocutaneous syndrome, Congenital malformation syndromes associated with short stature, Costello syndrome, Leopard syndrome and 2 more
NRAS 6 / 16 Cardiofaciocutaneous syndrome, Costello syndrome, Leopard syndrome, Myelomonocytic leukemia and 2 more
KRAS 5 / 16 Cardiofaciocutaneous syndrome, Costello syndrome, Myelomonocytic leukemia, Non-immune hydrops fetalis and 1 more
MAP2K1 5 / 16 Cardiofaciocutaneous syndrome, Costello syndrome, Leopard syndrome, Noonan syndrome and 1 more
RAF1 5 / 16 Cardiofaciocutaneous syndrome, Costello syndrome, Leopard syndrome, Noonan syndrome and 1 more
SHOC2 5 / 16 Cardiofaciocutaneous syndrome, Costello syndrome, Non-immune hydrops fetalis, Noonan syndrome and 1 more
SOS1 5 / 16 Blepharoptosis, Cardiofaciocutaneous syndrome, Corticobasal degeneration, Costello syndrome and 1 more
HRAS 4 / 16 Cardiofaciocutaneous syndrome, Costello syndrome, Non-immune hydrops fetalis, Noonan syndrome
MAP2K2 4 / 16 Cardiofaciocutaneous syndrome, Costello syndrome, Leopard syndrome, Noonan syndrome
RIT1 4 / 16 Cardiofaciocutaneous syndrome, Congenital malformation syndromes associated with short stature, Non-immune hydrops fetalis, Noonan syndrome
LRRC56 3 / 16 Costello syndrome, Non-immune hydrops fetalis, Noonan syndrome
LZTR1 3 / 16 Congenital malformation syndromes associated with short stature, Non-immune hydrops fetalis, Noonan syndrome
CBL 2 / 16 Myelomonocytic leukemia, Noonan syndrome
DHCR24 2 / 16 Desmosterolosis, Non-immune hydrops fetalis
EPHA2 2 / 16 Leopard syndrome, Noonan syndrome
FOXC2 2 / 16 Blepharoptosis, Non-immune hydrops fetalis
GALNT14 2 / 16 Congenital malrotation of intestine, Non-immune hydrops fetalis
MKRN2 2 / 16 Leopard syndrome, Noonan syndrome
MOCS3 2 / 16 Non-immune hydrops fetalis, sulfite oxidase deficiency due to molybdenum cofactor deficiency type B2
PPP1CB 2 / 16 Noonan syndrome, Noonan syndrome-like disorder with loose anagen hair
PPP1R13L 2 / 16 arrhythmogenic cardiomyopathy with variable ectodermal abnormalities, Leopard syndrome
RPL6 2 / 16 Leopard syndrome, Noonan syndrome
RRAS 2 / 16 Myelomonocytic leukemia, Noonan syndrome
SNAPC5 2 / 16 Cardiofaciocutaneous syndrome, Noonan syndrome
SOS2 2 / 16 Congenital malformation syndromes associated with short stature, Noonan syndrome
SPRED1 2 / 16 Costello syndrome, Noonan syndrome
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 ⇵
Ras signaling pathway
PTPN11, SOS1, SYNGAP1, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, SHOC2, SOS2, ANGPT2
 KEGG 22 / 237 10.5× 8.35e-17 3.83e-14 ✓ sig.
Proteoglycans in cancer
PTPN11, SOS1, BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, SOS2, FZD6, ROCK2
 KEGG 19 / 204 10.6× 1.24e-14 3.82e-12 ✓ sig.
Endometrial cancer
SOS1, BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, SOS2, PTEN, MAPK1, PIK3CA
 KEGG 12 / 59 23.0× 9.37e-14 2.43e-11 ✓ sig.
Chronic myeloid leukemia
PTPN11, SOS1, BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, SOS2, CBL, MAPK1
 KEGG 13 / 77 19.1× 1.07e-13 2.71e-11 ✓ sig.
EGFR tyrosine kinase inhibitor resistance
SOS1, BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, SOS2, NF1, PTEN, MAPK1
 KEGG 13 / 80 18.4× 1.79e-13 4.34e-11 ✓ sig.
Renal cell carcinoma
PTPN11, SOS1, BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, SOS2, MAPK1, PIK3CA
 KEGG 12 / 70 19.4× 8.22e-13 1.82e-10 ✓ sig.
MAPK signaling pathway
SOS1, BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, SOS2, DUSP4, ANGPT2, FLT4
 KEGG 20 / 299 7.6× 1.25e-12 2.69e-10 ✓ sig.
Glioma
SOS1, BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, SOS2, PTEN, MAPK1, PIK3CA
 KEGG 12 / 76 17.9× 2.29e-12 4.69e-10 ✓ sig.
RAS signaling downstream of NF1 loss-of-function variants
HRAS, KRAS, NRAS, SPRED1, NF1, SPRED2
 Reactome 6 / 7 97.1× 2.85e-12 5.67e-10 ✓ sig.
ErbB signaling pathway
SOS1, BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, SOS2, CBL, MAPK1, PIK3CA
 KEGG 12 / 86 15.8× 1.05e-11 1.87e-9 ✓ sig.
Acute myeloid leukemia
SOS1, BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, SOS2, MAPK1, PIK3CA
 KEGG 11 / 68 18.3× 1.50e-11 2.58e-9 ✓ sig.
Non-small cell lung cancer
SOS1, BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, SOS2, MAPK1, PIK3CA
 KEGG 11 / 73 17.1× 3.37e-11 5.38e-9 ✓ sig.
Breast cancer
SOS1, BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, SOS2, FLT4, FZD6, PTEN
 KEGG 14 / 148 10.7× 4.01e-11 6.31e-9 ✓ sig.
Phospholipase D signaling pathway
PTPN11, SOS1, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, SOS2, RRAS, MRAS, RRAS2
 KEGG 14 / 149 10.6× 4.39e-11 6.86e-9 ✓ sig.
Prostate cancer
SOS1, BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, SOS2, PTEN, MAPK1, PIK3CA
 KEGG 12 / 98 13.9× 5.12e-11 7.86e-9 ✓ 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 ⇵
Ras protein signal transduction
SOS1, SYNGAP1, HRAS, KRAS, NRAS, RIT1, SOS2, DHCR24, NF1, RRAS, MRAS, RRAS2
 GO:0007265 12 / 79 26.8× 2.19e-14 1.34e-11 ✓ sig.
Schwann cell development
SOS1, HRAS, MAP2K1, MAP2K2, RAF1, NF1, MAPK1
 GO:0014044 7 / 20 61.7× 1.13e-11 4.12e-9 ✓ sig.
MAPK cascade
LRRK2, BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, RAF1, NF1, PPP1CB, MAPK1
 GO:0000165 11 / 147 13.2× 7.18e-10 1.67e-7 ✓ sig.
face development
ANKRD11, BRAF, MAP2K1, MAP2K2, RAF1, MAPK1
 GO:0060324 6 / 22 48.1× 2.00e-9 4.13e-7 ✓ sig.
insulin-like growth factor receptor signaling pathway
SOS1, MAP2K1, MAP2K2, RAF1, MAPK1, PIK3CA
 GO:0048009 6 / 33 32.1× 2.82e-8 4.18e-6 ✓ sig.
regulation of intracellular signal transduction
LRRK2, SYNGAP1, CBL, NF1, RASA1, RASA2
 GO:1902531 6 / 40 26.4× 9.48e-8 1.15e-5 ✓ sig.
ERBB2-ERBB3 signaling pathway
MAP2K1, MAP2K2, RAF1, MAPK1
 GO:0038133 4 / 9 78.4× 1.21e-7 1.41e-5 ✓ sig.
Schwann cell migration
NF1, RRAS, RRAS2
 GO:0036135 3 / 3 176× 1.77e-7 1.96e-5 ✓ sig.
insulin receptor signaling pathway
FOXC2, SOS1, HRAS, RAF1, SOS2, MAPK1, PIK3CA
 GO:0008286 7 / 80 15.4× 3.50e-7 3.46e-5 ✓ sig.
thymus development
BRAF, MAP2K1, MAP2K2, RAF1, ASXL1, MAPK1
 GO:0048538 6 / 50 21.2× 3.75e-7 3.67e-5 ✓ sig.
thyroid gland development
BRAF, MAP2K1, MAP2K2, RAF1, MAPK1
 GO:0030878 5 / 30 29.4× 6.80e-7 6.06e-5 ✓ sig.
regulation of Golgi inheritance
MAP2K1, MAP2K2, MAPK1
 GO:0090170 3 / 4 132× 7.07e-7 6.27e-5 ✓ sig.
blood vessel morphogenesis
SOS1, ANGPT2, FLT4, EPHA2, RASA1
 GO:0048514 5 / 34 25.9× 1.30e-6 1.02e-4 ✓ sig.
regulation of long-term neuronal synaptic plasticity
SYNGAP1, HRAS, KRAS, NF1
 GO:0048169 4 / 18 39.2× 2.82e-6 1.89e-4 ✓ sig.
regulation of MAPK cascade
PTPN11, SYNGAP1, SHOC2, SPRED1, NF1
 GO:0043408 5 / 41 21.5× 3.40e-6 2.21e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Cardiofaciocutaneous syndrome Noonan syndrome 0.316 12 5.02e-33 1.80e-31 ✓ sig.
Costello syndrome Noonan syndrome 0.308 12 6.51e-32 2.24e-30 ✓ sig.
Cardiofaciocutaneous syndrome Costello syndrome 0.625 10 9.17e-32 3.12e-30 ✓ sig.
Leopard syndrome Noonan syndrome 0.225 9 5.10e-23 1.18e-21 ✓ sig.
Cardiofaciocutaneous syndrome Leopard syndrome 0.333 6 2.30e-17 4.04e-16 ✓ sig.
Costello syndrome Leopard syndrome 0.316 6 4.28e-17 7.42e-16 ✓ sig.
Leopard syndrome noonan syndrome with multiple lentigines 0.417 5 6.41e-17 1.10e-15 ✓ sig.
Cardiofaciocutaneous syndrome noonan syndrome with multiple lentigines 0.385 5 1.10e-16 1.86e-15 ✓ sig.
Costello syndrome noonan syndrome with multiple lentigines 0.357 5 1.79e-16 2.98e-15 ✓ sig.
Noonan syndrome noonan syndrome with multiple lentigines 0.132 5 6.05e-14 8.43e-13 ✓ sig.
Congenital malformation syndromes associated with short stature Noonan syndrome 0.128 5 3.62e-13 4.82e-12 ✓ sig.
Non-immune hydrops fetalis Noonan syndrome 0.092 7 1.08e-11 1.25e-10 ✓ sig.
Cardiofaciocutaneous syndrome Non-immune hydrops fetalis 0.094 5 1.32e-10 1.37e-9 ✓ sig.
Costello syndrome Non-immune hydrops fetalis 0.093 5 2.14e-10 2.20e-9 ✓ sig.
Cardiofaciocutaneous syndrome Congenital malformation syndromes associated with short stature 0.188 3 7.22e-9 6.36e-8 ✓ sig.
Cardiofaciocutaneous syndrome Myelomonocytic leukemia 0.150 3 4.33e-8 3.41e-7 ✓ sig.
Costello syndrome Myelomonocytic leukemia 0.143 3 5.62e-8 4.33e-7 ✓ sig.
Congenital malformation syndromes associated with short stature Non-immune hydrops fetalis 0.061 3 4.64e-7 3.06e-6 ✓ sig.
Congenital malformation syndromes associated with short stature noonan syndrome with multiple lentigines 0.200 2 1.26e-6 7.70e-6 ✓ sig.
Myelomonocytic leukemia noonan syndrome with multiple lentigines 0.143 2 3.79e-6 2.12e-5 ✓ sig.
Noonan syndrome Noonan syndrome-like disorder with loose anagen hair 0.053 2 5.62e-6 3.06e-5 ✓ sig.
Blepharoptosis Cardiofaciocutaneous syndrome 0.067 2 9.45e-5 3.38e-4 ✓ sig.
Blepharoptosis Costello syndrome 0.065 2 1.12e-4 3.90e-4 ✓ sig.
noonan syndrome with multiple lentigines Osteochondroma 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Congenital malformation syndromes associated with short stature Osteochondroma 0.143 1 3.90e-4 8.52e-4 ✓ sig.
arrhythmogenic cardiomyopathy with variable ectodermal abnormalities Leopard syndrome 0.083 1 7.14e-4 1.31e-3 ✓ sig.
Cardiofaciocutaneous syndrome Noonan syndrome-like disorder with loose anagen hair 0.071 1 1.56e-3 2.36e-3 ✓ sig.
Costello syndrome Noonan syndrome-like disorder with loose anagen hair 0.067 1 1.69e-3 2.51e-3 ✓ sig.
Non-immune hydrops fetalis sulfite oxidase deficiency due to molybdenum cofactor deficiency type B2 0.022 1 2.92e-3 3.87e-3 ✓ sig.
Desmosterolosis Non-immune hydrops fetalis 0.022 1 2.92e-3 3.87e-3 ✓ sig.
Congenital malrotation of intestine Non-immune hydrops fetalis 0.022 1 2.92e-3 3.87e-3 ✓ sig.
Cardiofaciocutaneous syndrome Corticobasal degeneration 0.053 1 5.44e-3 6.63e-3 ✓ sig.
Non-immune hydrops fetalis Noonan syndrome-like disorder with loose anagen hair 0.021 1 5.84e-3 7.05e-3 ✓ sig.
Corticobasal degeneration Costello syndrome 0.050 1 5.90e-3 7.11e-3 ✓ sig.
Blepharoptosis Corticobasal degeneration 0.038 1 8.61e-3 9.94e-3 ✓ sig.