Disease Clusters | GeDiPNet

Cluster 465

6 diseases · 15 shared-gene connections

6 Diseases

2 Unique genes

0.422 Avg. similarity score

Brain anomalies ectodermal dysplasia skeletal malformations hirschsprung disease syndrome Most-connected disease (5 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.

Brain anomalies ectodermal dysplasia skeletal malformations hirschsprung disease syndrome Bresek syndrome Ichthyosis follicularis, atrichia, and photophobia with or without brain anomalies, retardation, ectodermal dysplasia, skeletal malformations, hirschsprung disease, ear/eye anomalies, cleft palate/cryptorchidism, and kidney dysplasia/hypoplasia Ifap syndrome 1, with or without bresheck syndrome Keratosis follicularis spinulosa decalvans, x-linked Olmsted syndrome, x-linked

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

Disease ⇵	Connections in cluster ⇵	Significant partners ⇵	Curated genes ⇵
Brain anomalies ectodermal dysplasia skeletal malformations hirschsprung disease syndrome	5	5	1
Bresek syndrome	5	5	1
Ichthyosis follicularis, atrichia, and photophobia with or without brain anomalies, retardation, ectodermal dysplasia, skeletal malformations, hirschsprung disease, ear/eye anomalies, cleft palate/cryptorchidism, and kidney dysplasia/hypoplasia	5	5	1
Ifap syndrome 1, with or without bresheck syndrome	5	5	1
Keratosis follicularis spinulosa decalvans, x-linked	5	5	2
Olmsted syndrome, x-linked	5	5	2

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

Gene ⇵	Member diseases ⇵	Linked diseases
MBTPS2	6 / 6	Brain anomalies ectodermal dysplasia skeletal malformations hirschsprung disease syndrome, Bresek syndrome, Ichthyosis follicularis, atrichia, and photophobia with or without brain anomalies, retardation, ectodermal dysplasia, skeletal malformations, hirschsprung disease, ear/eye anomalies, cleft palate/cryptorchidism, and kidney dysplasia/hypoplasia, Ifap syndrome 1, with or without bresheck syndrome and 2 more
YY2	2 / 6	Keratosis follicularis spinulosa decalvans, x-linked, Olmsted syndrome, x-linked

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 ⇵
ATF6 (ATF6-alpha) activates chaperones MBTPS2	Reactome	1 / 4	1,501×	6.66e-4	8.31e-3 ✓ sig.
CREB3 factors activate genes MBTPS2	Reactome	1 / 5	1,201×	8.33e-4	9.85e-3 ✓ sig.
Regulation of cholesterol biosynthesis by SREBP (SREBF) MBTPS2	Reactome	1 / 7	858×	1.17e-3	1.27e-2 ✓ sig.
Polycomb repressive complex YY2	KEGG	1 / 83	72.3×	1.38e-2	6.92e-2
ATP-dependent chromatin remodeling YY2	KEGG	1 / 117	51.3×	1.94e-2	8.42e-2
Protein processing in endoplasmic reticulum MBTPS2	KEGG	1 / 171	35.1×	2.83e-2	1.04e-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 ⇵
bone maturation MBTPS2	GO:0070977	1 / 3	3,115×	3.21e-4	7.04e-3 ✓ sig.
regulation of response to endoplasmic reticulum stress MBTPS2	GO:1905897	1 / 4	2,336×	4.28e-4	8.53e-3 ✓ sig.
ATF6-mediated unfolded protein response MBTPS2	GO:0036500	1 / 8	1,168×	8.56e-4	1.33e-2 ✓ sig.
regulation of cholesterol biosynthetic process MBTPS2	GO:0045540	1 / 12	779×	1.28e-3	1.67e-2 ✓ sig.
membrane protein intracellular domain proteolysis MBTPS2	GO:0031293	1 / 14	667×	1.50e-3	1.82e-2 ✓ sig.
positive regulation of cholesterol biosynthetic process MBTPS2	GO:0045542	1 / 24	389×	2.57e-3	2.40e-2 ✓ sig.
NLS-bearing protein import into nucleus MBTPS2	GO:0006607	1 / 27	346×	2.89e-3	2.55e-2 ✓ sig.
mitotic G2 DNA damage checkpoint signaling MBTPS2	GO:0007095	1 / 36	260×	3.85e-3	2.94e-2 ✓ sig.
positive regulation of transcription by RNA polymerase II MBTPS2, YY2	GO:0045944	2 / 1,208	15.5×	4.18e-3	3.06e-2 ✓ sig.
endoplasmic reticulum unfolded protein response MBTPS2	GO:0030968	1 / 58	161×	6.20e-3	3.70e-2 ✓ sig.
cholesterol metabolic process MBTPS2	GO:0008203	1 / 107	87.3×	1.14e-2	4.96e-2 ✓ sig.
response to endoplasmic reticulum stress MBTPS2	GO:0034976	1 / 113	82.7×	1.21e-2	5.08e-2
protein maturation MBTPS2	GO:0051604	1 / 134	69.7×	1.43e-2	5.53e-2
steroid metabolic process MBTPS2	GO:0008202	1 / 135	69.2×	1.44e-2	5.54e-2
proteolysis MBTPS2	GO:0006508	1 / 613	15.2×	6.45e-2	1.26e-1

Pairs within this cluster, by significance

Disease A ⇵	Disease B ⇵	Similarity score ⇵	Shared genes ⇵	P-value ⇵	FDR q-value ⇵
Keratosis follicularis spinulosa decalvans, x-linked	Olmsted syndrome, x-linked	0.667	2	8.34e-9	6.60e-8 ✓ sig.
Brain anomalies ectodermal dysplasia skeletal malformations hirschsprung disease syndrome	Bresek syndrome	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Brain anomalies ectodermal dysplasia skeletal malformations hirschsprung disease syndrome	Ifap syndrome 1, with or without bresheck syndrome	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Brain anomalies ectodermal dysplasia skeletal malformations hirschsprung disease syndrome	Ichthyosis follicularis, atrichia, and photophobia with or without brain anomalies, retardation, ectodermal dysplasia, skeletal malformations, hirschsprung disease, ear/eye anomalies, cleft palate/cryptorchidism, and kidney dysplasia/hypoplasia	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Bresek syndrome	Ifap syndrome 1, with or without bresheck syndrome	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Bresek syndrome	Ichthyosis follicularis, atrichia, and photophobia with or without brain anomalies, retardation, ectodermal dysplasia, skeletal malformations, hirschsprung disease, ear/eye anomalies, cleft palate/cryptorchidism, and kidney dysplasia/hypoplasia	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Ichthyosis follicularis, atrichia, and photophobia with or without brain anomalies, retardation, ectodermal dysplasia, skeletal malformations, hirschsprung disease, ear/eye anomalies, cleft palate/cryptorchidism, and kidney dysplasia/hypoplasia	Ifap syndrome 1, with or without bresheck syndrome	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Brain anomalies ectodermal dysplasia skeletal malformations hirschsprung disease syndrome	Keratosis follicularis spinulosa decalvans, x-linked	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Brain anomalies ectodermal dysplasia skeletal malformations hirschsprung disease syndrome	Olmsted syndrome, x-linked	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Bresek syndrome	Keratosis follicularis spinulosa decalvans, x-linked	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Bresek syndrome	Olmsted syndrome, x-linked	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Ichthyosis follicularis, atrichia, and photophobia with or without brain anomalies, retardation, ectodermal dysplasia, skeletal malformations, hirschsprung disease, ear/eye anomalies, cleft palate/cryptorchidism, and kidney dysplasia/hypoplasia	Keratosis follicularis spinulosa decalvans, x-linked	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Ichthyosis follicularis, atrichia, and photophobia with or without brain anomalies, retardation, ectodermal dysplasia, skeletal malformations, hirschsprung disease, ear/eye anomalies, cleft palate/cryptorchidism, and kidney dysplasia/hypoplasia	Olmsted syndrome, x-linked	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Ifap syndrome 1, with or without bresheck syndrome	Keratosis follicularis spinulosa decalvans, x-linked	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Ifap syndrome 1, with or without bresheck syndrome	Olmsted syndrome, x-linked	0.333	1	1.29e-4	3.27e-4 ✓ sig.

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