Disease Clusters | GeDiPNet

Cluster 368

7 diseases · 15 shared-gene connections

7 Diseases

5 Unique genes

0.364 Avg. similarity score

Chronic progressive external ophthalmoplegia Most-connected disease (5 links)

Significant edges only (q < 0.05) Spacing Colour by

Disease Searched: Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant, 5 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.

Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant, 5 Chronic progressive external ophthalmoplegia Mitochondrial dna depletion syndrome 8a (encephalomyopathic type with renal tubulopathy) Progressive external ophthalmoplegia with mitochondrial dna deletions (autosomal dominant) Rod-cone dystrophy, sensorineural deafness, and fanconi-type renal dysfunction Camptocormia

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

Disease ⇵	Connections in cluster ⇵	Significant partners ⇵	Curated genes ⇵
Chronic progressive external ophthalmoplegia	5	5	2
Mitochondrial dna depletion syndrome 8a (encephalomyopathic type with renal tubulopathy)	5	5	1
Progressive external ophthalmoplegia with mitochondrial dna deletions (autosomal dominant)	5	5	1
Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant, 5	5	5	1
Rod-cone dystrophy, sensorineural deafness, and fanconi-type renal dysfunction	5	5	1
Camptocormia	4	4	4
Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 2	1	1	1

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

Gene ⇵	Member diseases ⇵	Linked diseases
RRM2B	6 / 7	Camptocormia, Chronic progressive external ophthalmoplegia, Mitochondrial dna depletion syndrome 8a (encephalomyopathic type with renal tubulopathy), Progressive external ophthalmoplegia with mitochondrial dna deletions (autosomal dominant) and 2 more
RNASEH1	2 / 7	Chronic progressive external ophthalmoplegia, Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 2

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)

None of these pathways reaches significance (all FDR q ≥ 0.05). They’re the best candidates found, but treat them as weak evidence for why this cluster groups together.

Pathway ⇵	Source ⇵	Overlap genes ⇵	Fold enrichment ⇵	P-value ⇵	FDR q-value ⇵
Interconversion of nucleotide di- and triphosphates RRM2B	Reactome	1 / 29	82.8×	1.20e-2	6.35e-2
DNA replication RNASEH1	KEGG	1 / 36	66.7×	1.49e-2	7.22e-2
Base excision repair POLG	KEGG	1 / 44	54.6×	1.82e-2	8.12e-2
Pyrimidine metabolism RRM2B	KEGG	1 / 58	41.4×	2.39e-2	9.49e-2
Glutathione metabolism RRM2B	KEGG	1 / 59	40.7×	2.43e-2	9.60e-2
Viral myocarditis MYH7	KEGG	1 / 70	34.3×	2.88e-2	1.06e-1
p53 signaling pathway RRM2B	KEGG	1 / 75	32.0×	3.08e-2	1.10e-1
Drug metabolism - other enzymes RRM2B	KEGG	1 / 81	29.7×	3.33e-2	1.15e-1
Nucleotide metabolism RRM2B	KEGG	1 / 85	28.3×	3.49e-2	1.18e-1
TP53 Regulates Metabolic Genes RRM2B	Reactome	1 / 86	27.9×	3.53e-2	1.19e-1
Cardiac muscle contraction MYH7	KEGG	1 / 87	27.6×	3.57e-2	1.19e-1
Hypertrophic cardiomyopathy MYH7	KEGG	1 / 99	24.3×	4.05e-2	1.28e-1
Dilated cardiomyopathy MYH7	KEGG	1 / 105	22.9×	4.30e-2	1.33e-1
Thyroid hormone signaling pathway MYH7	KEGG	1 / 122	19.7×	4.98e-2	1.44e-1
Purine metabolism RRM2B	KEGG	1 / 128	18.8×	5.22e-2	1.48e-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 ⇵
mitochondrial DNA replication RRM2B, POLG	GO:0006264	2 / 11	680×	3.15e-6	2.18e-4 ✓ sig.
deoxyribonucleoside triphosphate metabolic process RRM2B	GO:0009200	1 / 1	3,737×	2.68e-4	6.25e-3 ✓ sig.
regulation of slow-twitch skeletal muscle fiber contraction MYH7	GO:0031449	1 / 2	1,869×	5.35e-4	9.88e-3 ✓ sig.
ribonucleoside diphosphate metabolic process RRM2B	GO:0009185	1 / 3	1,246×	8.03e-4	1.28e-2 ✓ sig.
deoxyribonucleotide biosynthetic process RRM2B	GO:0009263	1 / 3	1,246×	8.03e-4	1.28e-2 ✓ sig.
2'-deoxyribonucleotide biosynthetic process RRM2B	GO:0009265	1 / 3	1,246×	8.03e-4	1.28e-2 ✓ sig.
regulation of cell fate commitment GDF3	GO:0010453	1 / 3	1,246×	8.03e-4	1.28e-2 ✓ sig.
regulation of the force of skeletal muscle contraction MYH7	GO:0014728	1 / 3	1,246×	8.03e-4	1.28e-2 ✓ sig.
DNA replication proofreading POLG	GO:0045004	1 / 3	1,246×	8.03e-4	1.28e-2 ✓ sig.
negative regulation of epidermal cell differentiation GDF3	GO:0045605	1 / 3	1,246×	8.03e-4	1.28e-2 ✓ sig.
DNA replication, removal of RNA primer RNASEH1	GO:0043137	1 / 4	934×	1.07e-3	1.51e-2 ✓ sig.
formation of anatomical boundary GDF3	GO:0048859	1 / 4	934×	1.07e-3	1.51e-2 ✓ sig.
positive regulation of G0 to G1 transition RRM2B	GO:0070318	1 / 5	747×	1.34e-3	1.71e-2 ✓ sig.
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway GDF3	GO:0090092	1 / 6	623×	1.60e-3	1.88e-2 ✓ sig.
positive regulation of mitotic cell cycle phase transition RRM2B	GO:1901992	1 / 7	534×	1.87e-3	2.05e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵	Disease B ⇵	Similarity score ⇵	Shared genes ⇵	P-value ⇵	FDR q-value ⇵
Mitochondrial dna depletion syndrome 8a (encephalomyopathic type with renal tubulopathy)	Rod-cone dystrophy, sensorineural deafness, and fanconi-type renal dysfunction	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Mitochondrial dna depletion syndrome 8a (encephalomyopathic type with renal tubulopathy)	Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant, 5	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Mitochondrial dna depletion syndrome 8a (encephalomyopathic type with renal tubulopathy)	Progressive external ophthalmoplegia with mitochondrial dna deletions (autosomal dominant)	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Progressive external ophthalmoplegia with mitochondrial dna deletions (autosomal dominant)	Rod-cone dystrophy, sensorineural deafness, and fanconi-type renal dysfunction	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Progressive external ophthalmoplegia with mitochondrial dna deletions (autosomal dominant)	Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant, 5	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant, 5	Rod-cone dystrophy, sensorineural deafness, and fanconi-type renal dysfunction	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Chronic progressive external ophthalmoplegia	Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 2	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Chronic progressive external ophthalmoplegia	Rod-cone dystrophy, sensorineural deafness, and fanconi-type renal dysfunction	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Chronic progressive external ophthalmoplegia	Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant, 5	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Chronic progressive external ophthalmoplegia	Mitochondrial dna depletion syndrome 8a (encephalomyopathic type with renal tubulopathy)	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Chronic progressive external ophthalmoplegia	Progressive external ophthalmoplegia with mitochondrial dna deletions (autosomal dominant)	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Camptocormia	Rod-cone dystrophy, sensorineural deafness, and fanconi-type renal dysfunction	0.200	1	2.58e-4	5.38e-4 ✓ sig.
Camptocormia	Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant, 5	0.200	1	2.58e-4	5.38e-4 ✓ sig.
Camptocormia	Mitochondrial dna depletion syndrome 8a (encephalomyopathic type with renal tubulopathy)	0.200	1	2.58e-4	5.38e-4 ✓ sig.
Camptocormia	Progressive external ophthalmoplegia with mitochondrial dna deletions (autosomal dominant)	0.200	1	2.58e-4	5.38e-4 ✓ sig.

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