Disease Clusters | GeDiPNet

Cluster 217

9 diseases · 22 shared-gene connections

9 Diseases

6 Unique genes

0.393 Avg. similarity score

Encephalopathy Most-connected disease (7 links)

Significant edges only (q < 0.05) Spacing Colour by

Disease Searched: Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies 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.

Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies Encephalopathy Coma Hemiplegic migraine-developmental and epileptic encephalopathy spectrum Migraine, familial basilar Neuronal migration disorder with epilepsy

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

Disease ⇵	Connections in cluster ⇵	Significant partners ⇵	Curated genes ⇵
Encephalopathy	7	7	5
Coma	6	6	1
Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies	6	6	1
Hemiplegic migraine-developmental and epileptic encephalopathy spectrum	6	6	1
Migraine, familial basilar	6	6	1
Neuronal migration disorder with epilepsy	6	6	1
Benign familial infantile convulsions	5	5	1
Early-onset dystonia with spastic paraplegia	1	1	2
Epileptic encephalopathy, early infantile, 82	1	1	1

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

Gene ⇵	Member diseases ⇵	Linked diseases
ATP1A2	7 / 9	Benign familial infantile convulsions, Coma, Encephalopathy, Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies and 3 more
GOT2	2 / 9	Encephalopathy, Epileptic encephalopathy, early infantile, 82
PTPN1	2 / 9	Early-onset dystonia with spastic paraplegia, Encephalopathy

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 ⇵
PTK6 Down-Regulation PTPN1	Reactome	1 / 3	667×	1.50e-3	1.54e-2 ✓ sig.
MECP2 regulates neuronal receptors and channels PTPN1	Reactome	1 / 4	500×	2.00e-3	1.90e-2 ✓ sig.
Phenylalanine, tyrosine and tryptophan biosynthesis GOT2	KEGG	1 / 6	334×	2.99e-3	2.54e-2 ✓ sig.
Chemical carcinogenesis - reactive oxygen species ATP5MC3, PTPN1	KEGG	2 / 227	17.6×	5.07e-3	3.68e-2 ✓ sig.
Thermogenesis ATP5MC3, COX16	KEGG	2 / 234	17.1×	5.38e-3	3.83e-2 ✓ sig.
Aspartate and asparagine metabolism GOT2	Reactome	1 / 12	167×	5.98e-3	4.10e-2 ✓ sig.
Growth hormone receptor signaling PTPN1	Reactome	1 / 14	143×	6.98e-3	4.53e-2 ✓ sig.
Glutamate and glutamine metabolism GOT2	Reactome	1 / 14	143×	6.98e-3	4.53e-2 ✓ sig.
Phenylalanine metabolism GOT2	KEGG	1 / 16	125×	7.97e-3	4.94e-2 ✓ sig.
Formation of ATP by chemiosmotic coupling ATP5MC3	Reactome	1 / 18	111×	8.96e-3	5.31e-2
Cristae formation ATP5MC3	Reactome	1 / 18	111×	8.96e-3	5.31e-2
Negative regulation of MET activity PTPN1	Reactome	1 / 21	95.3×	1.04e-2	5.84e-2
Arginine biosynthesis GOT2	KEGG	1 / 23	87.0×	1.14e-2	6.18e-2
Proximal tubule bicarbonate reclamation ATP1A2	KEGG	1 / 23	87.0×	1.14e-2	6.18e-2
Integrin signaling PTPN1	Reactome	1 / 23	87.0×	1.14e-2	6.18e-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 ⇵
olfactory cortex development ATP1A2	GO:0021989	1 / 1	3,115×	3.21e-4	7.04e-3 ✓ sig.
regulation of glutamate uptake involved in transmission of nerve impulse ATP1A2	GO:0051946	1 / 2	1,557×	6.42e-4	1.11e-2 ✓ sig.
L-glutamate catabolic process to aspartate GOT2	GO:0019550	1 / 2	1,557×	6.42e-4	1.11e-2 ✓ sig.
regulation of hepatocyte growth factor receptor signaling pathway PTPN1	GO:1902202	1 / 2	1,557×	6.42e-4	1.11e-2 ✓ sig.
negative regulation of striated muscle contraction ATP1A2	GO:0045988	1 / 3	1,038×	9.63e-4	1.42e-2 ✓ sig.
negative regulation of calcium ion transmembrane transport ATP1A2	GO:1903170	1 / 3	1,038×	9.63e-4	1.42e-2 ✓ sig.
aspartate biosynthetic process GOT2	GO:0006532	1 / 3	1,038×	9.63e-4	1.42e-2 ✓ sig.
L-aspartate catabolic process GOT2	GO:0006533	1 / 3	1,038×	9.63e-4	1.42e-2 ✓ sig.
trans-4-hydroxy-L-proline catabolic process GOT2	GO:0019470	1 / 4	779×	1.28e-3	1.67e-2 ✓ sig.
amygdala development ATP1A2	GO:0021764	1 / 4	779×	1.28e-3	1.67e-2 ✓ sig.
insulin receptor recycling PTPN1	GO:0038020	1 / 4	779×	1.28e-3	1.67e-2 ✓ sig.
proton transmembrane transport ATP5MC3, ATP1A2	GO:1902600	2 / 181	34.4×	1.36e-3	1.74e-2 ✓ sig.
negative regulation of translation in response to stress RNH1	GO:0032055	1 / 5	623×	1.60e-3	1.88e-2 ✓ sig.
regulation of type I interferon-mediated signaling pathway PTPN1	GO:0060338	1 / 5	623×	1.60e-3	1.88e-2 ✓ sig.
L-glutamate catabolic process GOT2	GO:0006538	1 / 5	623×	1.60e-3	1.88e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵	Disease B ⇵	Similarity score ⇵	Shared genes ⇵	P-value ⇵	FDR q-value ⇵
Benign familial infantile convulsions	Hemiplegic migraine-developmental and epileptic encephalopathy spectrum	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Migraine, familial basilar	Neuronal migration disorder with epilepsy	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Hemiplegic migraine-developmental and epileptic encephalopathy spectrum	Migraine, familial basilar	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Hemiplegic migraine-developmental and epileptic encephalopathy spectrum	Neuronal migration disorder with epilepsy	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies	Migraine, familial basilar	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies	Neuronal migration disorder with epilepsy	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies	Hemiplegic migraine-developmental and epileptic encephalopathy spectrum	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Coma	Migraine, familial basilar	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Coma	Neuronal migration disorder with epilepsy	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Coma	Hemiplegic migraine-developmental and epileptic encephalopathy spectrum	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Coma	Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Benign familial infantile convulsions	Migraine, familial basilar	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Benign familial infantile convulsions	Coma	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Benign familial infantile convulsions	Neuronal migration disorder with epilepsy	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Benign familial infantile convulsions	Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Encephalopathy	Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies	0.167	1	3.23e-4	6.41e-4 ✓ sig.
Encephalopathy	Hemiplegic migraine-developmental and epileptic encephalopathy spectrum	0.167	1	3.23e-4	6.41e-4 ✓ sig.
Encephalopathy	Neuronal migration disorder with epilepsy	0.167	1	3.23e-4	6.41e-4 ✓ sig.
Coma	Encephalopathy	0.167	1	3.23e-4	6.41e-4 ✓ sig.
Encephalopathy	Migraine, familial basilar	0.167	1	3.23e-4	6.41e-4 ✓ sig.
Encephalopathy	Epileptic encephalopathy, early infantile, 82	0.167	1	3.23e-4	6.41e-4 ✓ sig.
Early-onset dystonia with spastic paraplegia	Encephalopathy	0.143	1	6.46e-4	1.09e-3 ✓ sig.

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