Disease Clusters | GeDiPNet

Cluster 572

5 diseases · 10 shared-gene connections

5 Diseases

10 Unique genes

0.289 Avg. similarity score

Microphthalmia syndromic type 3, optic nerve hypoplasia and abnormalities of the central nervous system Most-connected disease (4 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.

Microphthalmia syndromic type 3, optic nerve hypoplasia and abnormalities of the central nervous system Microphthalmia, syndromic 3 Optic nerve hypoplasia and abnormalities of the central nervous system Sensorineural hearing loss Thoracic neoplasms

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

Disease ⇵	Connections in cluster ⇵	Significant partners ⇵	Curated genes ⇵
Microphthalmia syndromic type 3, optic nerve hypoplasia and abnormalities of the central nervous system	4	4	1
Microphthalmia, syndromic 3	4	4	1
Optic nerve hypoplasia and abnormalities of the central nervous system	4	4	1
Sensorineural hearing loss	4	4	9
Thoracic neoplasms	4	4	2

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

Gene ⇵	Member diseases ⇵	Linked diseases
SOX2	5 / 5	Microphthalmia syndromic type 3, optic nerve hypoplasia and abnormalities of the central nervous system, Microphthalmia, syndromic 3, Optic nerve hypoplasia and abnormalities of the central nervous system, Sensorineural hearing loss and 1 more

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 ⇵
POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation SOX2	Reactome	1 / 3	400×	2.50e-3	2.23e-2 ✓ sig.
Disinhibition of SNARE formation STXBP3	Reactome	1 / 5	240×	4.16e-3	3.21e-2 ✓ sig.
Netrin-1 signaling NTN1	Reactome	1 / 8	150×	6.64e-3	4.39e-2 ✓ sig.
DCC mediated attractive signaling NTN1	Reactome	1 / 11	109×	9.12e-3	5.37e-2
Axon guidance NTN1, PLXNB2	KEGG	2 / 183	13.1×	9.59e-3	5.55e-2
POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation SOX2	Reactome	1 / 13	92.4×	1.08e-2	5.96e-2
Polymerase switching RFC4	Reactome	1 / 14	85.8×	1.16e-2	6.22e-2
Translesion synthesis by REV1 RFC4	Reactome	1 / 16	75.1×	1.32e-2	6.74e-2
Translesion synthesis by POLK RFC4	Reactome	1 / 17	70.6×	1.41e-2	6.99e-2
Translesion synthesis by POLI RFC4	Reactome	1 / 17	70.6×	1.41e-2	6.99e-2
Polymerase switching on the C-strand of the telomere RFC4	Reactome	1 / 17	70.6×	1.41e-2	6.99e-2
Transcriptional regulation of pluripotent stem cells SOX2	Reactome	1 / 17	70.6×	1.41e-2	6.99e-2
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane TUBB4B	Reactome	1 / 18	66.7×	1.49e-2	7.22e-2
Cilium Assembly TUBB4B	Reactome	1 / 19	63.2×	1.57e-2	7.46e-2
Translesion Synthesis by POLH RFC4	Reactome	1 / 19	63.2×	1.57e-2	7.46e-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 ⇵
pituitary gland development SOX2, LHX3	GO:0021983	2 / 30	125×	1.11e-4	3.34e-3 ✓ sig.
brain development SOX2, PLXNB2, STXBP3	GO:0007420	3 / 244	23.0×	2.47e-4	5.89e-3 ✓ sig.
inner ear development SOX2, LHX3	GO:0048839	2 / 54	69.2×	3.63e-4	7.69e-3 ✓ sig.
regulation of interleukin-18 production NLRP12	GO:0032661	1 / 1	1,869×	5.35e-4	9.88e-3 ✓ sig.
regulation of glial cell migration NTN1	GO:1903975	1 / 1	1,869×	5.35e-4	9.88e-3 ✓ sig.
positive regulation of cell differentiation SMARCA4, SOX2	GO:0045597	2 / 83	45.0×	8.57e-4	1.33e-2 ✓ sig.
prolactin secreting cell differentiation LHX3	GO:0060127	1 / 2	934×	1.07e-3	1.51e-2 ✓ sig.
regulation of myofibroblast cell apoptotic process SOX2	GO:1904520	1 / 2	934×	1.07e-3	1.51e-2 ✓ sig.
medial motor column neuron differentiation LHX3	GO:0021526	1 / 2	934×	1.07e-3	1.51e-2 ✓ sig.
negative regulation of Toll signaling pathway NLRP12	GO:0045751	1 / 2	934×	1.07e-3	1.51e-2 ✓ sig.
positive regulation of glucose mediated signaling pathway SMARCA4	GO:1902661	1 / 3	623×	1.60e-3	1.88e-2 ✓ sig.
glial cell fate commitment SOX2	GO:0021781	1 / 3	623×	1.60e-3	1.88e-2 ✓ sig.
chemorepulsion of axon NTN1	GO:0061643	1 / 3	623×	1.60e-3	1.88e-2 ✓ sig.
Cdc42 protein signal transduction NTN1	GO:0032488	1 / 3	623×	1.60e-3	1.88e-2 ✓ sig.
regulation of cell migration NTN1, PLXNB2	GO:0030334	2 / 122	30.6×	1.84e-3	2.04e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵	Disease B ⇵	Similarity score ⇵	Shared genes ⇵	P-value ⇵	FDR q-value ⇵
Microphthalmia syndromic type 3, optic nerve hypoplasia and abnormalities of the central nervous system	Microphthalmia, syndromic 3	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Microphthalmia syndromic type 3, optic nerve hypoplasia and abnormalities of the central nervous system	Optic nerve hypoplasia and abnormalities of the central nervous system	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Microphthalmia, syndromic 3	Optic nerve hypoplasia and abnormalities of the central nervous system	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Microphthalmia syndromic type 3, optic nerve hypoplasia and abnormalities of the central nervous system	Thoracic neoplasms	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Microphthalmia, syndromic 3	Thoracic neoplasms	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Optic nerve hypoplasia and abnormalities of the central nervous system	Thoracic neoplasms	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Microphthalmia syndromic type 3, optic nerve hypoplasia and abnormalities of the central nervous system	Sensorineural hearing loss	0.100	1	5.81e-4	1.00e-3 ✓ sig.
Microphthalmia, syndromic 3	Sensorineural hearing loss	0.100	1	5.81e-4	1.00e-3 ✓ sig.
Optic nerve hypoplasia and abnormalities of the central nervous system	Sensorineural hearing loss	0.100	1	5.81e-4	1.00e-3 ✓ sig.
Sensorineural hearing loss	Thoracic neoplasms	0.091	1	1.16e-3	1.73e-3 ✓ sig.

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