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 275

7 diseases · 7 shared-gene connections
7 Diseases
45 Unique genes
0.051 Avg. similarity score
Teratozoospermia Most-connected disease (5 links)
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Disease Searched: spermatogenic failure 38 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 ⇵
Teratozoospermia 5 5 27
Congenital impairment of spermatozoa motility 3 3 23
spermatogenic failure 38 2 2 1
Male infertility teratozoospermia 1 1 2
Ruijs-aalfs syndrome 1 1 1
X-linked intellectual disability, Cabezas type 1 1 1
ciliary dyskinesia, primary, 45 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
ARMC2 3 / 7 Congenital impairment of spermatozoa motility, spermatogenic failure 38, Teratozoospermia
AKAP4 2 / 7 Congenital impairment of spermatozoa motility, Teratozoospermia
CFAP251 2 / 7 Congenital impairment of spermatozoa motility, Male infertility teratozoospermia
CFAP43 2 / 7 Congenital impairment of spermatozoa motility, Teratozoospermia
CUL4B 2 / 7 Teratozoospermia, X-linked intellectual disability, Cabezas type
DNAH1 2 / 7 Congenital impairment of spermatozoa motility, Teratozoospermia
SPRTN 2 / 7 Ruijs-aalfs syndrome, Teratozoospermia
TTC12 2 / 7 ciliary dyskinesia, primary, 45, Teratozoospermia
TTC21A 2 / 7 Congenital impairment of spermatozoa motility, Teratozoospermia
USP26 2 / 7 Congenital impairment of spermatozoa motility, Teratozoospermia
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 ⇵
Nectin/Necl trans heterodimerization
NECTIN2, NECTIN3
 Reactome 2 / 7 76.3× 2.85e-4 5.22e-3 ✓ sig.
Adherens junctions interactions
NECTIN2, NECTIN3
 Reactome 2 / 32 16.7× 6.34e-3 5.23e-2
NOSIP mediated eNOS trafficking
NOS3
 Reactome 1 / 2 133× 7.48e-3 5.81e-2
Dual Incision in GG-NER
CUL4B, GTF2H1
 Reactome 2 / 41 13.0× 1.03e-2 7.13e-2
Nitric oxide stimulates guanylate cyclase
NOS3
 Reactome 1 / 3 89.0× 1.12e-2 7.51e-2
Formation of Incision Complex in GG-NER
CUL4B, GTF2H1
 Reactome 2 / 43 12.4× 1.12e-2 7.53e-2
Transcription-Coupled Nucleotide Excision Repair (TC-NER)
CUL4B, GTF2H1
 Reactome 2 / 45 11.9× 1.23e-2 7.96e-2
Formation of TC-NER Pre-Incision Complex
CUL4B, GTF2H1
 Reactome 2 / 54 9.9× 1.74e-2 9.78e-2
NOSTRIN mediated eNOS trafficking
NOS3
 Reactome 1 / 5 53.4× 1.86e-2 1.02e-1
Nucleotide excision repair
CUL4B, GTF2H1
 KEGG 2 / 63 8.5× 2.32e-2 1.15e-1
Gap-filling DNA repair synthesis and ligation in TC-NER
CUL4B, GTF2H1
 Reactome 2 / 65 8.2× 2.46e-2 1.20e-1
Dual incision in TC-NER
CUL4B, GTF2H1
 Reactome 2 / 66 8.1× 2.53e-2 1.21e-1
Virion - Herpesvirus
NECTIN2
 KEGG 1 / 9 29.7× 3.32e-2 1.40e-1
Sperm Motility And Taxes
CATSPER1
 Reactome 1 / 9 29.7× 3.32e-2 1.40e-1
Bacterial invasion of epithelial cells
SEPTIN12, MAD2L2
 KEGG 2 / 78 6.8× 3.44e-2 1.43e-1

Enriched GO Terms (Biological Process, a second line of biological evidence)

GO term ⇵ GO ID ⇵ Overlap genes ⇵ Fold enrichment ⇵ P-value ⇵ FDR q-value ⇵
sperm axoneme assembly
ARMC2, CFAP43, CFAP44, CFAP65, CFAP69, DNAH1, FSIP2, SPEF2, TTC12, TTLL5
 GO:0007288 10 / 31 134× 9.56e-20 1.45e-16 ✓ sig.
spermatogenesis
AKAP4, ARMC2, CATSPER1, CFAP43, CFAP44, CFAP69, SEPTIN12, SLC26A8, SPAG17, SPEF2, SSX1, TTC21A
 GO:0007283 19 / 556 14.2× 8.72e-18 9.88e-15 ✓ sig.
flagellated sperm motility
AKAP4, ARMC2, CATSPER1, CFAP251, CFAP43, CFAP44, CFAP65, CFAP69, DNAH1, DRC1, FSIP2, TTC21A
 GO:0030317 13 / 142 38.0× 9.54e-18 1.06e-14 ✓ sig.
cilium organization
ARMC2, CFAP43, CFAP44, DRC1, TTC29, NECTIN2
 GO:0044782 6 / 40 62.3× 4.98e-10 1.18e-7 ✓ sig.
cilium movement
CFAP251, CFAP43, CFAP70, TTC29, CFAP91, HYDIN
 GO:0003341 6 / 48 51.9× 1.57e-9 3.26e-7 ✓ sig.
axonemal central apparatus assembly
SPAG17, CFAP91, HYDIN
 GO:1904158 3 / 6 208× 2.60e-7 2.73e-5 ✓ sig.
spermatid development
TTC21A, ADCY10, NECTIN2, PMFBP1, SPATA16, YTHDC2
 GO:0007286 6 / 120 20.8× 4.10e-7 4.00e-5 ✓ sig.
epithelial cilium movement involved in extracellular fluid movement
DNAH1, SPAG17, SPEF2, ADCY10
 GO:0003351 4 / 26 63.9× 4.22e-7 4.09e-5 ✓ sig.
establishment of localization in cell
AKAP4, CFAP43, SPAG17, ATG5, NECTIN2, NOS3
 GO:0051649 6 / 147 16.9× 1.35e-6 1.07e-4 ✓ sig.
cilium-dependent cell motility
DNAH1, DNAH17, DRC1
 GO:0060285 3 / 12 104× 2.83e-6 1.94e-4 ✓ sig.
cell differentiation
ARMC2, CATSPER1, CFAP69, SEPTIN12, SLC26A8, SPAG17, SPEF2, TTC21A, CFAP91, CDK16, SPATA16, YTHDC2
 GO:0030154 12 / 1,051 4.7× 4.81e-6 2.96e-4 ✓ sig.
cell projection organization
AK7, AKAP4, CFAP43, CFAP65, SPAG17, TTC12
 GO:0030030 6 / 214 11.6× 1.18e-5 6.01e-4 ✓ sig.
cilium movement involved in cell motility
DNAH1, DNAH17, DNAH10
 GO:0060294 3 / 27 46.1× 3.67e-5 1.45e-3 ✓ sig.
nucleus organization
ARMC2, CFAP43, CFAP44
 GO:0006997 3 / 34 36.6× 7.41e-5 2.48e-3 ✓ sig.
fertilization
ACTL9, NECTIN2, NECTIN3
 GO:0009566 3 / 54 23.1× 2.97e-4 6.81e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Congenital impairment of spermatozoa motility Teratozoospermia 0.133 6 1.58e-12 1.90e-11 ✓ sig.
Congenital impairment of spermatozoa motility spermatogenic failure 38 0.042 1 1.49e-3 2.31e-3 ✓ sig.
ciliary dyskinesia, primary, 45 Teratozoospermia 0.036 1 1.75e-3 2.61e-3 ✓ sig.
Ruijs-aalfs syndrome Teratozoospermia 0.036 1 1.75e-3 2.61e-3 ✓ sig.
spermatogenic failure 38 Teratozoospermia 0.036 1 1.75e-3 2.61e-3 ✓ sig.
Teratozoospermia X-linked intellectual disability, Cabezas type 0.036 1 1.75e-3 2.61e-3 ✓ sig.
Congenital impairment of spermatozoa motility Male infertility teratozoospermia 0.040 1 2.99e-3 3.95e-3 ✓ sig.