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 336
6
Diseases
6
Unique genes
0.255
Avg. similarity score
Parkinsonism-dystonia
Most-connected disease (5 links)
Disease
Pinned (dragged)
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Parkinsonism-dystonia
Dopamine transporter deficiency syndrome
Mild cognitive impairment
SLC6A3-related dopamine transporter deficiency syndrome
Combined oxidative phosphorylation defect
brain dopamine-serotonin vesicular transport disease
Member diseases (most connected first ‐ the cluster's core)
| Disease ⇵ | Connections in cluster ⇵ | Significant partners ⇵ | Curated genes ⇵ |
|---|---|---|---|
| Parkinsonism-dystonia | 5 | 5 | 3 |
| Dopamine transporter deficiency syndrome | 3 | 3 | 1 |
| Mild cognitive impairment | 3 | 3 | 4 |
| SLC6A3-related dopamine transporter deficiency syndrome | 3 | 3 | 1 |
| Combined oxidative phosphorylation defect | 1 | 1 | 1 |
| brain dopamine-serotonin vesicular transport disease | 1 | 1 | 1 |
Top shared genes (genes linked to 2+ member diseases)
| Gene ⇵ | Member diseases ⇵ | Linked diseases |
|---|---|---|
| SLC6A3 | 4 / 6 | Dopamine transporter deficiency syndrome, Mild cognitive impairment, Parkinsonism-dystonia, SLC6A3-related dopamine transporter deficiency syndrome |
| SLC18A2 | 2 / 6 | brain dopamine-serotonin vesicular transport disease, Parkinsonism-dystonia |
| WARS2 | 2 / 6 | Combined oxidative phosphorylation defect, Parkinsonism-dystonia |
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 ⇵ |
|---|---|---|---|---|---|
| Na+/Cl- dependent neurotransmitter transporters | Reactome | 2 / 19 | 211× | 3.54e-5 | 9.60e-4 ✓ sig. |
| Cocaine addiction | KEGG | 2 / 49 | 81.7× | 2.42e-4 | 4.54e-3 ✓ sig. |
| Amphetamine addiction | KEGG | 2 / 69 | 58.0× | 4.81e-4 | 7.73e-3 ✓ sig. |
| Dopamine clearance from the synaptic cleft | Reactome | 1 / 1 | 2,002× | 5.00e-4 | 7.96e-3 ✓ sig. |
| Defective SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS) | Reactome | 1 / 1 | 2,002× | 5.00e-4 | 7.96e-3 ✓ sig. |
| Synaptic vesicle cycle | KEGG | 2 / 79 | 50.7× | 6.30e-4 | 9.55e-3 ✓ sig. |
| Dopaminergic synapse | KEGG | 2 / 132 | 30.3× | 1.75e-3 | 2.07e-2 ✓ sig. |
| Alcoholism | KEGG | 2 / 188 | 21.3× | 3.51e-3 | 3.43e-2 ✓ sig. |
| Advanced glycosylation endproduct receptor signaling | Reactome | 1 / 8 | 250× | 3.99e-3 | 3.77e-2 ✓ sig. |
| Mitochondrial tRNA aminoacylation | Reactome | 1 / 14 | 143× | 6.98e-3 | 5.45e-2 |
| Parkinson disease | KEGG | 2 / 268 | 14.9× | 7.01e-3 | 5.47e-2 |
| Serotonin Neurotransmitter Release Cycle | Reactome | 1 / 18 | 111× | 8.96e-3 | 6.42e-2 |
| Norepinephrine Neurotransmitter Release Cycle | Reactome | 1 / 18 | 111× | 8.96e-3 | 6.42e-2 |
| Dopamine Neurotransmitter Release Cycle | Reactome | 1 / 23 | 87.0× | 1.14e-2 | 7.44e-2 |
| TRAF6 mediated NF-kB activation | Reactome | 1 / 24 | 83.4× | 1.19e-2 | 7.61e-2 |
Enriched GO Terms (Biological Process, a second line of biological evidence)
| GO term ⇵ | GO ID ⇵ | Overlap genes ⇵ | Fold enrichment ⇵ | P-value ⇵ | FDR q-value ⇵ |
|---|---|---|---|---|---|
| monoamine transport | GO:0015844 | 2 / 9 | 692× | 3.09e-6 | 2.04e-4 ✓ sig. |
| dopamine transport | GO:0015872 | 2 / 10 | 623× | 3.86e-6 | 2.44e-4 ✓ sig. |
| neurotransmitter transport | GO:0006836 | 2 / 57 | 109× | 1.36e-4 | 3.80e-3 ✓ sig. |
| regulation of CD4-positive, alpha-beta T cell activation | GO:2000514 | 1 / 1 | 3,115× | 3.21e-4 | 7.03e-3 ✓ sig. |
| mitochondrial tryptophanyl-tRNA aminoacylation | GO:0070183 | 1 / 1 | 3,115× | 3.21e-4 | 7.03e-3 ✓ sig. |
| L-alanine catabolic process, by transamination | GO:0019481 | 1 / 1 | 3,115× | 3.21e-4 | 7.03e-3 ✓ sig. |
| N(omega),N(omega)-dimethyl-L-arginine catabolic process | GO:2001299 | 1 / 1 | 3,115× | 3.21e-4 | 7.03e-3 ✓ sig. |
| serotonin secretion by mast cell | GO:0002552 | 1 / 1 | 3,115× | 3.21e-4 | 7.03e-3 ✓ sig. |
| somato-dendritic dopamine secretion | GO:0099123 | 1 / 1 | 3,115× | 3.21e-4 | 7.03e-3 ✓ sig. |
| locomotory behavior | GO:0007626 | 2 / 99 | 62.9× | 4.11e-4 | 8.37e-3 ✓ sig. |
| glycine biosynthetic process, by transamination of glyoxylate | GO:0019265 | 1 / 2 | 1,557× | 6.42e-4 | 1.13e-2 ✓ sig. |
| negative regulation of blood circulation | GO:1903523 | 1 / 2 | 1,557× | 6.42e-4 | 1.13e-2 ✓ sig. |
| regulation of T cell mediated cytotoxicity | GO:0001914 | 1 / 2 | 1,557× | 6.42e-4 | 1.13e-2 ✓ sig. |
| negative regulation of connective tissue replacement involved in inflammatory response wound healing | GO:1904597 | 1 / 2 | 1,557× | 6.42e-4 | 1.13e-2 ✓ sig. |
| positive regulation of DNA-templated DNA replication | GO:2000105 | 1 / 2 | 1,557× | 6.42e-4 | 1.13e-2 ✓ sig. |
Pairs within this cluster, by significance
| Disease A ⇵ | Disease B ⇵ | Similarity score ⇵ | Shared genes ⇵ | P-value ⇵ | FDR q-value ⇵ |
|---|---|---|---|---|---|
| Dopamine transporter deficiency syndrome | SLC6A3-related dopamine transporter deficiency syndrome | 0.500 | 1 | 6.49e-5 | 2.34e-4 ✓ sig. |
| brain dopamine-serotonin vesicular transport disease | Parkinsonism-dystonia | 0.250 | 1 | 1.95e-4 | 5.28e-4 ✓ sig. |
| Combined oxidative phosphorylation defect | Parkinsonism-dystonia | 0.250 | 1 | 1.95e-4 | 5.28e-4 ✓ sig. |
| Dopamine transporter deficiency syndrome | Parkinsonism-dystonia | 0.250 | 1 | 1.95e-4 | 5.28e-4 ✓ sig. |
| Parkinsonism-dystonia | SLC6A3-related dopamine transporter deficiency syndrome | 0.250 | 1 | 1.95e-4 | 5.28e-4 ✓ sig. |
| Dopamine transporter deficiency syndrome | Mild cognitive impairment | 0.200 | 1 | 2.60e-4 | 6.40e-4 ✓ sig. |
| Mild cognitive impairment | SLC6A3-related dopamine transporter deficiency syndrome | 0.200 | 1 | 2.60e-4 | 6.40e-4 ✓ sig. |
| Mild cognitive impairment | Parkinsonism-dystonia | 0.143 | 1 | 7.79e-4 | 1.39e-3 ✓ sig. |