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 121

12 diseases · 20 shared-gene connections
12 Diseases
47 Unique genes
0.163 Avg. similarity score
Cancer predisposition Most-connected disease (8 links)
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Disease Searched: Fanconi anemia complementation group j 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 ⇵
Cancer predisposition 8 8 9
Hereditary breast and ovarian cancer syndrome 7 7 15
Familial ovarian cancer 6 6 6
Hereditary breast cancer 4 4 32
Breast-ovarian cancer, familial, susceptibility to, 4 3 3 1
Fanconi anemia complementation group n 3 3 1
Fallopian tube serous adenocarcinoma 2 2 13
Fanconi anemia complementation group j 2 2 1
Fanconi anemia, complementation group s 2 2 1
Fanconi anemia complementation group U 1 1 1
Recon progeroid syndrome 1 1 1
T-cell lymphoma, subcutaneous panniculitis-like 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
BRCA1 6 / 12 Cancer predisposition, Fallopian tube serous adenocarcinoma, Familial ovarian cancer, Fanconi anemia, complementation group s and 2 more
PALB2 5 / 12 Cancer predisposition, Familial ovarian cancer, Fanconi anemia complementation group n, Hereditary breast and ovarian cancer syndrome and 1 more
BRCA2 4 / 12 Cancer predisposition, Familial ovarian cancer, Hereditary breast and ovarian cancer syndrome, Hereditary breast cancer
BRIP1 4 / 12 Familial ovarian cancer, Fanconi anemia complementation group j, Hereditary breast and ovarian cancer syndrome, Hereditary breast cancer
CHEK2 4 / 12 Cancer predisposition, Fallopian tube serous adenocarcinoma, Hereditary breast and ovarian cancer syndrome, Hereditary breast cancer
RAD51D 4 / 12 Breast-ovarian cancer, familial, susceptibility to, 4, Cancer predisposition, Familial ovarian cancer, Hereditary breast and ovarian cancer syndrome
ATM 3 / 12 Cancer predisposition, Hereditary breast and ovarian cancer syndrome, Hereditary breast cancer
BARD1 3 / 12 Cancer predisposition, Hereditary breast and ovarian cancer syndrome, Hereditary breast cancer
RAD51C 3 / 12 Cancer predisposition, Familial ovarian cancer, Hereditary breast and ovarian cancer syndrome
HAVCR2 2 / 12 Cancer predisposition, T-cell lymphoma, subcutaneous panniculitis-like
MRE11 2 / 12 Hereditary breast and ovarian cancer syndrome, Hereditary breast cancer
NBN 2 / 12 Hereditary breast and ovarian cancer syndrome, Hereditary breast cancer
RAD50 2 / 12 Hereditary breast and ovarian cancer syndrome, Hereditary breast cancer
RAD51 2 / 12 Hereditary breast and ovarian cancer syndrome, Hereditary breast cancer
RECQL 2 / 12 Hereditary breast cancer, Recon progeroid syndrome
TP53 2 / 12 Fallopian tube serous adenocarcinoma, Hereditary breast and ovarian cancer syndrome
XRCC2 2 / 12 Fanconi anemia complementation group U, Hereditary breast 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 ⇵
Resolution of D-loop Structures through Holliday Junction Intermediates
BRCA1, BRCA2, RAD51C, RAD51D, PALB2, ATM, BARD1, BRIP1, MRE11, NBN, RAD50, RAD51
 Reactome 15 / 33 116× 6.30e-29 1.75e-25 ✓ sig.
Homologous DNA Pairing and Strand Exchange
BRCA1, BRCA2, RAD51C, RAD51D, PALB2, ATM, BARD1, BRIP1, MRE11, NBN, RAD50, RAD51
 Reactome 13 / 25 133× 4.11e-26 7.84e-23 ✓ sig.
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
BRCA1, BRCA2, RAD51C, RAD51D, PALB2, ATM, BARD1, BRIP1, MRE11, NBN, RAD50, RAD51
 Reactome 13 / 26 128× 8.19e-26 1.50e-22 ✓ sig.
Homologous recombination
BRCA1, BRCA2, RAD51C, RAD51D, PALB2, ATM, BARD1, BRIP1, MRE11, NBN, RAD50, RAD51
 KEGG 14 / 41 87.3× 7.60e-25 1.21e-21 ✓ sig.
Presynaptic phase of homologous DNA pairing and strand exchange
BRCA1, BRCA2, RAD51C, RAD51D, ATM, BARD1, BRIP1, MRE11, NBN, RAD50, RAD51, XRCC2
 Reactome 13 / 39 85.2× 6.18e-23 7.68e-20 ✓ sig.
HDR through Homologous Recombination (HRR)
BRCA1, BRCA2, RAD51C, RAD51D, PALB2, ATM, BARD1, BRIP1, MRE11, NBN, RAD50, RAD51
 Reactome 13 / 48 69.2× 1.43e-21 1.39e-18 ✓ sig.
Fanconi anemia pathway
BRCA1, BRCA2, RAD51C, PALB2, BRIP1, RAD51, ATRIP, FANCM, MLH1, PMS2, SLX4
 KEGG 11 / 54 52.1× 7.92e-17 3.38e-14 ✓ sig.
HDR through Single Strand Annealing (SSA)
BRCA1, ATM, BARD1, BRIP1, MRE11, NBN, RAD50, RAD51, ATRIP
 Reactome 9 / 37 62.2× 1.10e-14 3.10e-12 ✓ sig.
G2/M DNA damage checkpoint
BRCA1, ATM, BARD1, BRIP1, CHEK2, MRE11, NBN, RAD50, TP53, ATRIP
 Reactome 10 / 84 30.4× 6.77e-13 1.36e-10 ✓ sig.
Regulation of TP53 Activity through Phosphorylation
BRCA1, ATM, BARD1, BRIP1, CHEK2, MRE11, NBN, RAD50, TP53, ATRIP
 Reactome 10 / 92 27.8× 1.73e-12 3.11e-10 ✓ sig.
TP53 Regulates Transcription of DNA Repair Genes
BRCA1, RAD51D, ATM, TP53, CDK9, MLH1, MSH2, PMS2
 Reactome 8 / 65 31.5× 1.26e-10 1.43e-8 ✓ sig.
Cellular senescence
ATM, CHEK2, MRE11, NBN, PTEN, RAD50, TP53, PIK3CA, RB1, MTOR
 KEGG 10 / 157 16.3× 3.74e-10 3.85e-8 ✓ sig.
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
BRCA1, ATM, BARD1, CHEK2, MRE11, NBN, RAD50, TP53
 Reactome 8 / 76 26.9× 4.55e-10 4.57e-8 ✓ sig.
Sensing of DNA Double Strand Breaks
ATM, MRE11, NBN, RAD50
 Reactome 4 / 6 170× 3.07e-9 2.57e-7 ✓ sig.
Processing of DNA double-strand break ends
BRCA1, ATM, BARD1, BRIP1, MRE11, NBN, RAD50, ATRIP
 Reactome 8 / 98 20.9× 3.56e-9 2.94e-7 ✓ 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 ⇵
DNA repair
BRCA1, BRCA2, RAD51C, RAD51D, PALB2, ATM, BARD1, BRIP1, CHEK2, MRE11, NBN, RAD50
 GO:0006281 27 / 420 25.6× 8.81e-33 6.21e-29 ✓ sig.
DNA damage response
BRCA1, BRCA2, RAD51C, RAD51D, PALB2, ATM, BARD1, BRIP1, CHEK2, MRE11, NBN, RAD50
 GO:0006974 28 / 577 19.3× 1.08e-30 6.76e-27 ✓ sig.
double-strand break repair via homologous recombination
BRCA1, BRCA2, RAD51C, RAD51D, PALB2, ATM, MRE11, NBN, RAD50, RAD51, RAD54L, XRCC2
 GO:0000724 15 / 119 50.1× 2.92e-22 6.43e-19 ✓ sig.
DNA recombination
BRCA1, BRCA2, RAD51C, RAD51D, PALB2, MRE11, RAD50, RAD51, RAD54L, XRCC2, GEN1, RECQL
 GO:0006310 13 / 110 47.0× 5.84e-19 8.02e-16 ✓ sig.
double-strand break repair
BRCA1, BRCA2, ATM, BRIP1, CHEK2, MRE11, NBN, RAD50, TP53, RAD54L, MSH2
 GO:0006302 11 / 87 50.3× 1.76e-16 1.63e-13 ✓ sig.
homologous recombination
BRCA1, BARD1, BRIP1, MRE11, NBN, RAD50, FANCM
 GO:0035825 7 / 12 232× 3.13e-16 2.77e-13 ✓ sig.
reciprocal meiotic recombination
RAD51C, RAD51D, ATM, MRE11, RAD50, RAD51, RAD54L, MLH1
 GO:0007131 8 / 33 96.4× 1.13e-14 7.66e-12 ✓ sig.
DNA strand resection involved in replication fork processing
BRCA1, ATM, BARD1, MRE11, NBN, RAD50
 GO:0110025 6 / 14 170× 5.37e-13 2.65e-10 ✓ sig.
telomere maintenance via recombination
BRCA2, RAD51C, RAD51D, RAD50, RAD51
 GO:0000722 5 / 11 181× 3.69e-11 1.24e-8 ✓ sig.
regulation of cell cycle
BRCA1, RAD51D, ATM, BARD1, NBN, PTEN, TP53, CDK9, MSH2, RB1, KAT7
 GO:0051726 11 / 262 16.7× 3.72e-11 1.25e-8 ✓ sig.
chromosome organization
BRCA2, RAD51D, MRE11, RAD50, TP53, RAD54L, RB1
 GO:0051276 7 / 51 54.6× 4.25e-11 1.41e-8 ✓ sig.
intrinsic apoptotic signaling pathway in response to DNA damage
BRCA1, BRCA2, ATM, CHEK2, MLH1, MSH2, MSH6
 GO:0008630 7 / 54 51.5× 6.47e-11 2.07e-8 ✓ sig.
somatic recombination of immunoglobulin gene segments
MLH1, MSH2, MSH6, PMS2
 GO:0016447 4 / 6 265× 5.25e-10 1.34e-7 ✓ sig.
replication fork processing
BRCA2, RAD51, CDK9, FANCM, GEN1, RECQL
 GO:0031297 6 / 41 58.2× 7.65e-10 1.84e-7 ✓ sig.
response to X-ray
BRCA2, RAD51, TP53, XRCC2, MSH2
 GO:0010165 5 / 19 105× 9.15e-10 2.15e-7 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hereditary breast and ovarian cancer syndrome Hereditary breast cancer 0.314 11 1.00e-28 1.91e-27 ✓ sig.
Cancer predisposition Hereditary breast and ovarian cancer syndrome 0.500 8 3.30e-25 5.68e-24 ✓ sig.
Familial ovarian cancer Hereditary breast and ovarian cancer syndrome 0.400 6 1.57e-19 2.25e-18 ✓ sig.
Cancer predisposition Familial ovarian cancer 0.455 5 1.02e-16 1.32e-15 ✓ sig.
Cancer predisposition Hereditary breast cancer 0.171 6 3.22e-15 3.92e-14 ✓ sig.
Cancer predisposition Fallopian tube serous adenocarcinoma 0.100 2 1.98e-5 1.03e-4 ✓ sig.
Fallopian tube serous adenocarcinoma Hereditary breast and ovarian cancer syndrome 0.080 2 4.98e-5 1.98e-4 ✓ sig.
Breast-ovarian cancer, familial, susceptibility to, 4 Familial ovarian cancer 0.143 1 3.87e-4 7.33e-4 ✓ sig.
Familial ovarian cancer Fanconi anemia complementation group n 0.143 1 3.87e-4 7.33e-4 ✓ sig.
Familial ovarian cancer Fanconi anemia complementation group j 0.143 1 3.87e-4 7.33e-4 ✓ sig.
Familial ovarian cancer Fanconi anemia, complementation group s 0.143 1 3.87e-4 7.33e-4 ✓ sig.
Cancer predisposition T-cell lymphoma, subcutaneous panniculitis-like 0.100 1 5.81e-4 1.00e-3 ✓ sig.
Cancer predisposition Fanconi anemia, complementation group s 0.100 1 5.81e-4 1.00e-3 ✓ sig.
Cancer predisposition Fanconi anemia complementation group n 0.100 1 5.81e-4 1.00e-3 ✓ sig.
Breast-ovarian cancer, familial, susceptibility to, 4 Cancer predisposition 0.100 1 5.81e-4 1.00e-3 ✓ sig.
Fanconi anemia complementation group n Hereditary breast and ovarian cancer syndrome 0.067 1 9.04e-4 1.41e-3 ✓ sig.
Fanconi anemia complementation group j Hereditary breast and ovarian cancer syndrome 0.067 1 9.04e-4 1.41e-3 ✓ sig.
Breast-ovarian cancer, familial, susceptibility to, 4 Hereditary breast and ovarian cancer syndrome 0.067 1 9.04e-4 1.41e-3 ✓ sig.
Fanconi anemia complementation group U Hereditary breast cancer 0.031 1 2.00e-3 2.72e-3 ✓ sig.
Hereditary breast cancer Recon progeroid syndrome 0.031 1 2.00e-3 2.72e-3 ✓ sig.