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 84

13 diseases · 28 shared-gene connections
13 Diseases
58 Unique genes
0.209 Avg. similarity score
Medullary thyroid cancer Most-connected disease (8 links)
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Disease Searched: Neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities 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 ⇵
Medullary thyroid cancer 8 8 5
Laryngeal carcinoma 6 6 15
Linear nevus sebaceous syndrome 6 6 6
Schimmelpenning-feuerstein-mims syndrome 6 6 3
Follicular thyroid cancer 5 5 7
Malignant struma ovarii 5 5 8
Nonmedullary thyroid cancer 4 4 7
Laryngeal neoplasms 3 3 6
Male reproductive system disease 3 3 4
Papillary thyroid cancer 3 3 14
Pulmonary hypoplasia 3 3 1
Thyroid gland neoplasms 3 3 21
Neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
HRAS 8 / 13 Follicular thyroid cancer, Laryngeal carcinoma, Linear nevus sebaceous syndrome, Malignant struma ovarii and 4 more
NRAS 8 / 13 Follicular thyroid cancer, Laryngeal carcinoma, Linear nevus sebaceous syndrome, Malignant struma ovarii and 4 more
BRAF 4 / 13 Linear nevus sebaceous syndrome, Malignant struma ovarii, Papillary thyroid cancer, Thyroid gland neoplasms
KRAS 4 / 13 Laryngeal carcinoma, Linear nevus sebaceous syndrome, Malignant struma ovarii, Schimmelpenning-feuerstein-mims syndrome
RET 4 / 13 Malignant struma ovarii, Medullary thyroid cancer, Papillary thyroid cancer, Thyroid gland neoplasms
WNT7B 4 / 13 Laryngeal carcinoma, Laryngeal neoplasms, Male reproductive system disease, Pulmonary hypoplasia
CCDC6 3 / 13 Malignant struma ovarii, Papillary thyroid cancer, Thyroid gland neoplasms
NKX2-1 3 / 13 Medullary thyroid cancer, Nonmedullary thyroid cancer, Papillary thyroid cancer
SRGAP1 3 / 13 Follicular thyroid cancer, Medullary thyroid cancer, Nonmedullary thyroid cancer
ATXN10 2 / 13 Laryngeal carcinoma, Laryngeal neoplasms
MINPP1 2 / 13 Follicular thyroid cancer, Nonmedullary thyroid cancer
NCOA4 2 / 13 Malignant struma ovarii, Thyroid gland neoplasms
PAX8 2 / 13 Follicular thyroid cancer, Thyroid gland neoplasms
PPARG 2 / 13 Follicular thyroid cancer, Thyroid gland neoplasms
PRKG1 2 / 13 Laryngeal carcinoma, Laryngeal neoplasms
SH3BP4 2 / 13 Laryngeal carcinoma, Laryngeal neoplasms
WARS1 2 / 13 Neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities, Papillary thyroid cancer
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 ⇵
Thyroid cancer
HRAS, KRAS, NRAS, PAX8, PPARG, RET, BRAF, CCDC6, NCOA4, TP53
 KEGG 10 / 37 56.0× 9.61e-16 3.31e-13 ✓ sig.
Non-small cell lung cancer
HRAS, KRAS, NRAS, RET, BRAF, CDKN2A, TP53, JAK3
 KEGG 8 / 73 22.7× 1.89e-9 1.65e-7 ✓ sig.
Prostate cancer
PDGFRA, HRAS, KRAS, NRAS, BRAF, ZEB1, TP53, FGFR2
 KEGG 8 / 98 16.9× 2.02e-8 1.37e-6 ✓ sig.
Pathways in cancer
PDGFRA, WNT7B, HRAS, KRAS, NRAS, PAX8, PPARG, RET, BRAF, CCDC6, CDKN2A, NCOA4
 KEGG 15 / 533 5.8× 2.13e-8 1.44e-6 ✓ sig.
Bladder cancer
HRAS, KRAS, NRAS, BRAF, CDKN2A, TP53
 KEGG 6 / 41 30.3× 3.84e-8 2.42e-6 ✓ sig.
Central carbon metabolism in cancer
PDGFRA, HRAS, KRAS, NRAS, RET, TP53, FGFR2
 KEGG 7 / 71 20.4× 4.41e-8 2.73e-6 ✓ sig.
Melanoma
PDGFRA, HRAS, KRAS, NRAS, BRAF, CDKN2A, TP53
 KEGG 7 / 73 19.9× 5.37e-8 3.24e-6 ✓ sig.
Glioma
PDGFRA, HRAS, KRAS, NRAS, BRAF, CDKN2A, TP53
 KEGG 7 / 76 19.1× 7.12e-8 4.15e-6 ✓ sig.
RAS GTPase cycle mutants
HRAS, KRAS, NRAS
 Reactome 3 / 3 207× 1.07e-7 5.93e-6 ✓ sig.
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants
PDGFRA, HRAS, KRAS, NRAS
 Reactome 4 / 12 69.0× 2.35e-7 1.19e-5 ✓ sig.
Signaling by PDGFRA extracellular domain mutants
PDGFRA, HRAS, KRAS, NRAS
 Reactome 4 / 12 69.0× 2.35e-7 1.19e-5 ✓ sig.
RAF activation
HRAS, KRAS, NRAS, BRAF, PPP2R5C
 Reactome 5 / 32 32.4× 4.02e-7 1.89e-5 ✓ sig.
Negative regulation of MAPK pathway
HRAS, KRAS, NRAS, BRAF, PPP2R5C
 Reactome 5 / 38 27.2× 9.79e-7 4.09e-5 ✓ sig.
Activation of RAS in B cells
HRAS, KRAS, NRAS
 Reactome 3 / 5 124× 1.06e-6 4.39e-5 ✓ sig.
Chronic myeloid leukemia
HRAS, KRAS, NRAS, BRAF, CDKN2A, TP53
 KEGG 6 / 77 16.1× 1.77e-6 6.82e-5 ✓ 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 ⇵
thyroid gland development
CGA, PAX8, NKX2-1, FOXE1, BRAF
 GO:0030878 5 / 30 53.7× 3.24e-8 4.91e-6 ✓ sig.
Ras protein signal transduction
RGL1, HRAS, KRAS, NRAS, CDKN2A, TP53
 GO:0007265 6 / 79 24.5× 1.60e-7 1.89e-5 ✓ sig.
interleukin-2-mediated signaling pathway
CD7, SECTM1, JAK3
 GO:0038110 3 / 12 80.5× 6.12e-6 3.72e-4 ✓ sig.
mesenchymal cell differentiation
SNAI1, SNAI2, FGFR2
 GO:0048762 3 / 13 74.4× 7.94e-6 4.55e-4 ✓ sig.
central nervous system development
NPAS2, VCAN, PAX8, ZEB1, ZEB2, TP53
 GO:0007417 6 / 158 12.2× 9.35e-6 5.17e-4 ✓ sig.
positive regulation of gene expression
HRAS, KRAS, PPARG, RET, NKX2-1, BRAF, WARS1, CDKN2A, TP53
 GO:0010628 9 / 504 5.8× 2.31e-5 1.03e-3 ✓ sig.
white fat cell differentiation
PDGFRA, PPARG, SNAI2
 GO:0050872 3 / 19 50.9× 2.65e-5 1.14e-3 ✓ sig.
animal organ morphogenesis
PDGFRA, HRAS, NKX2-1, BRAF, FGFR2
 GO:0009887 5 / 130 12.4× 5.14e-5 1.89e-3 ✓ sig.
negative regulation of keratinocyte proliferation
SNAI2, ZEB1, FGFR2
 GO:0010839 3 / 24 40.3× 5.48e-5 1.98e-3 ✓ sig.
negative regulation of vitamin D biosynthetic process
SNAI1, SNAI2
 GO:0010957 2 / 4 161× 5.66e-5 2.02e-3 ✓ sig.
roof of mouth development
PDGFRA, FOXE1, SNAI1, SNAI2
 GO:0060021 4 / 70 18.4× 6.58e-5 2.26e-3 ✓ sig.
MAPK cascade
HRAS, KRAS, NRAS, RET, BRAF
 GO:0000165 5 / 147 11.0× 9.22e-5 2.91e-3 ✓ sig.
metanephric epithelium development
WNT7B, PAX8
 GO:0072207 2 / 5 129× 9.41e-5 2.95e-3 ✓ sig.
regulation of smooth muscle cell differentiation
ZEB1, FGFR2
 GO:0051150 2 / 5 129× 9.41e-5 2.95e-3 ✓ sig.
positive regulation of DNA-templated transcription
NPAS2, PAX8, PPARG, RET, NKX2-1, FOXE1, SNAI1, CDKN2A, NCOA4, TP53
 GO:0045893 10 / 778 4.1× 1.26e-4 3.65e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Malignant struma ovarii Thyroid gland neoplasms 0.227 5 1.25e-14 1.49e-13 ✓ sig.
Medullary thyroid cancer Nonmedullary thyroid cancer 0.444 4 7.30e-14 8.31e-13 ✓ sig.
Follicular thyroid cancer Nonmedullary thyroid cancer 0.364 4 5.11e-13 5.59e-12 ✓ sig.
Laryngeal carcinoma Laryngeal neoplasms 0.250 4 4.47e-12 4.61e-11 ✓ sig.
Follicular thyroid cancer Thyroid gland neoplasms 0.167 4 7.06e-11 6.68e-10 ✓ sig.
Malignant struma ovarii Medullary thyroid cancer 0.333 3 3.23e-10 2.90e-9 ✓ sig.
Follicular thyroid cancer Medullary thyroid cancer 0.300 3 5.65e-10 4.99e-9 ✓ sig.
Medullary thyroid cancer Thyroid gland neoplasms 0.130 3 1.84e-8 1.42e-7 ✓ sig.
Linear nevus sebaceous syndrome Schimmelpenning-feuerstein-mims syndrome 0.400 2 5.00e-8 3.63e-7 ✓ sig.
Medullary thyroid cancer Schimmelpenning-feuerstein-mims syndrome 0.333 2 8.34e-8 5.85e-7 ✓ sig.
Malignant struma ovarii Schimmelpenning-feuerstein-mims syndrome 0.286 2 1.25e-7 8.63e-7 ✓ sig.
Follicular thyroid cancer Schimmelpenning-feuerstein-mims syndrome 0.250 2 1.75e-7 1.18e-6 ✓ sig.
Nonmedullary thyroid cancer Schimmelpenning-feuerstein-mims syndrome 0.250 2 1.75e-7 1.18e-6 ✓ sig.
Linear nevus sebaceous syndrome Medullary thyroid cancer 0.250 2 5.00e-7 3.18e-6 ✓ sig.
Laryngeal carcinoma Schimmelpenning-feuerstein-mims syndrome 0.143 2 6.50e-7 4.06e-6 ✓ sig.
Linear nevus sebaceous syndrome Malignant struma ovarii 0.222 2 7.50e-7 4.63e-6 ✓ sig.
Follicular thyroid cancer Linear nevus sebaceous syndrome 0.200 2 1.05e-6 6.38e-6 ✓ sig.
Linear nevus sebaceous syndrome Nonmedullary thyroid cancer 0.200 2 1.05e-6 6.38e-6 ✓ sig.
Laryngeal carcinoma Linear nevus sebaceous syndrome 0.125 2 3.90e-6 2.20e-5 ✓ sig.
Laryngeal carcinoma Medullary thyroid cancer 0.118 2 6.49e-6 3.57e-5 ✓ sig.
Medullary thyroid cancer Papillary thyroid cancer 0.118 2 6.49e-6 3.57e-5 ✓ sig.
Malignant struma ovarii Papillary thyroid cancer 0.111 2 9.74e-6 5.27e-5 ✓ sig.
Male reproductive system disease Pulmonary hypoplasia 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Laryngeal neoplasms Pulmonary hypoplasia 0.143 1 3.87e-4 7.33e-4 ✓ sig.
Neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities Papillary thyroid cancer 0.071 1 8.39e-4 1.34e-3 ✓ sig.
Laryngeal carcinoma Pulmonary hypoplasia 0.071 1 8.39e-4 1.34e-3 ✓ sig.
Laryngeal neoplasms Male reproductive system disease 0.100 1 1.55e-3 2.19e-3 ✓ sig.
Laryngeal carcinoma Male reproductive system disease 0.059 1 3.35e-3 4.22e-3 ✓ sig.