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Cluster 395

5 diseases · 5 shared-gene connections

5 Diseases

19 Unique genes

0.115 Avg. similarity score

Hemiparkinsonism Most-connected disease (3 links)

Significant edges only (q < 0.05) Spacing Colour by

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.

Hemiparkinsonism Secondary parkinson disease Parkinsonian-pyramidal syndrome Thyroid hemiagenesis Vesiculobullous skin disease

Member diseases (most connected first ‐ the cluster's core)

Disease ⇵	Connections in cluster ⇵	Significant partners ⇵	Curated genes ⇵
Hemiparkinsonism	3	3	3
Secondary parkinson disease	3	3	15
Parkinsonian-pyramidal syndrome	2	2	2
Thyroid hemiagenesis	1	1	2
Vesiculobullous skin disease	1	1	1

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

Gene ⇵	Member diseases ⇵	Linked diseases
SNCA	3 / 5	Hemiparkinsonism, Parkinsonian-pyramidal syndrome, Secondary parkinson disease
PRKN	2 / 5	Secondary parkinson disease, Vesiculobullous skin disease
VPS13C	2 / 5	Hemiparkinsonism, Thyroid hemiagenesis

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 ⇵
Parkinson disease SNCA, PRKN, SLC18A2, PSMD3	KEGG	4 / 268	9.4×	7.21e-4	1.06e-2 ✓ sig.
Hh mutants that don't undergo autocatalytic processing are degraded by ERAD SHH, PSMD3	Reactome	2 / 56	22.6×	3.47e-3	3.41e-2 ✓ sig.
Hedgehog ligand biogenesis SHH, PSMD3	Reactome	2 / 60	21.1×	3.97e-3	3.76e-2 ✓ sig.
Inhibition of nitric oxide production NOS2	Reactome	1 / 3	211×	4.74e-3	4.23e-2 ✓ sig.
Nitric oxide stimulates guanylate cyclase NOS2	Reactome	1 / 3	211×	4.74e-3	4.23e-2 ✓ sig.
Mitochondrial transcription initiation TFAM	Reactome	1 / 3	211×	4.74e-3	4.23e-2 ✓ sig.
Pathways of neurodegeneration - multiple diseases SNCA, NOS2, PRKN, PSMD3	KEGG	4 / 480	5.3×	6.05e-3	4.96e-2 ✓ sig.
HHAT G278V abrogates palmitoylation of Hh-Np SHH	Reactome	1 / 4	158×	6.31e-3	5.10e-2
Neurotransmitter clearance BCHE	Reactome	1 / 4	158×	6.31e-3	5.10e-2
ABC-family proteins mediated transport ABCB1, PSMD3	Reactome	2 / 81	15.6×	7.13e-3	5.54e-2
Synthesis of 5-eicosatetraenoic acids PON1	Reactome	1 / 6	105×	9.46e-3	6.63e-2
Release of Hh-Np from the secreting cell SHH	Reactome	1 / 7	90.3×	1.10e-2	7.27e-2
Ligand-receptor interactions SHH	Reactome	1 / 7	90.3×	1.10e-2	7.27e-2
Antigen processing: Ubiquitination & Proteasome degradation PRKN, FBXO7, PSMD3	Reactome	3 / 309	6.1×	1.20e-2	7.65e-2
Amyloid fiber formation SNCA, PRKN	Reactome	2 / 109	11.6×	1.26e-2	7.86e-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 ⇵
response to amphetamine CNR2, RGS2, SLC18A2	GO:0001975	3 / 31	95.2×	3.93e-6	2.48e-4 ✓ sig.
regulation of locomotion SNCA, FBXO7	GO:0040012	2 / 6	328×	1.47e-5	7.04e-4 ✓ sig.
dopamine uptake involved in synaptic transmission SNCA, PRKN	GO:0051583	2 / 6	328×	1.47e-5	7.04e-4 ✓ sig.
negative regulation of neuron apoptotic process SNCA, GDNF, PRKN, FBXO7	GO:0043524	4 / 160	24.6×	1.81e-5	8.31e-4 ✓ sig.
response to lipopolysaccharide SNCA, ABCB1, CNR2, NOS2	GO:0032496	4 / 161	24.4×	1.86e-5	8.46e-4 ✓ sig.
cellular response to manganese ion ATP13A2, PRKN	GO:0071287	2 / 7	281×	2.05e-5	9.16e-4 ✓ sig.
adult locomotory behavior SNCA, GDNF, PRKN	GO:0008344	3 / 56	52.7×	2.39e-5	1.03e-3 ✓ sig.
cellular response to L-glutamate ABCB1, PRKN	GO:1905232	2 / 9	219×	3.51e-5	1.38e-3 ✓ sig.
regulation of protein localization to nucleus ATP13A2, SHH	GO:1900180	2 / 10	197×	4.39e-5	1.63e-3 ✓ sig.
response to toxic substance FMC1, PON1, SLC18A2	GO:0009636	3 / 83	35.5×	7.78e-5	2.51e-3 ✓ sig.
negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway PRKN, FBXO7	GO:1903377	2 / 14	141×	8.85e-5	2.76e-3 ✓ sig.
response to xenobiotic stimulus SNCA, ABCB1, BCHE, PRKN	GO:0009410	4 / 248	15.9×	1.00e-4	3.03e-3 ✓ sig.
regulation of dopamine secretion SNCA, PRKN	GO:0014059	2 / 15	131×	1.02e-4	3.07e-3 ✓ sig.
synaptic transmission, dopaminergic SNCA, PRKN	GO:0001963	2 / 15	131×	1.02e-4	3.07e-3 ✓ sig.
positive regulation of mitophagy PRKN, FBXO7	GO:1901526	2 / 15	131×	1.02e-4	3.07e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵	Disease B ⇵	Similarity score ⇵	Shared genes ⇵	P-value ⇵	FDR q-value ⇵
Hemiparkinsonism	Parkinsonian-pyramidal syndrome	0.200	1	3.90e-4	8.52e-4 ✓ sig.
Hemiparkinsonism	Thyroid hemiagenesis	0.200	1	3.90e-4	8.52e-4 ✓ sig.
Secondary parkinson disease	Vesiculobullous skin disease	0.063	1	9.74e-4	1.64e-3 ✓ sig.
Parkinsonian-pyramidal syndrome	Secondary parkinson disease	0.059	1	1.95e-3	2.81e-3 ✓ sig.
Hemiparkinsonism	Secondary parkinson disease	0.056	1	2.92e-3	3.87e-3 ✓ sig.

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