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Cluster 107

12 diseases · 17 shared-gene connections

12 Diseases

29 Unique genes

0.161 Avg. similarity score

Hallervorden spatz 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.

Hallervorden spatz syndrome Neurodegeneration with brain iron accumulation Palmoplantar keratoderma with congenital alopecia Hallermanns syndrome Erythrokeratodermia variabilis Greither disease

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

Disease ⇵	Connections in cluster ⇵	Significant partners ⇵	Curated genes ⇵
Hallervorden spatz syndrome	5	5	7
Neurodegeneration with brain iron accumulation	5	5	14
Palmoplantar keratoderma with congenital alopecia	5	5	1
Hallermanns syndrome	4	4	2
Erythrokeratodermia variabilis	3	3	10
Greither disease	3	3	4
Bilateral microphthalmos	2	2	5
Pantothenate kinase-associated neurodegeneration	2	2	1
neurodegeneration with brain iron accumulation 4	2	2	1
erythrokeratodermia variabilis et progressiva 4	1	1	1
hereditary spastic paraplegia 35	1	1	1
kufor-rakeb syndrome	1	1	1

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

Gene ⇵	Member diseases ⇵	Linked diseases
GJA1	6 / 12	Bilateral microphthalmos, Erythrokeratodermia variabilis, Greither disease, Hallermanns syndrome and 2 more
C19ORF12	3 / 12	Hallervorden spatz syndrome, Neurodegeneration with brain iron accumulation, neurodegeneration with brain iron accumulation 4
PANK2	3 / 12	Hallervorden spatz syndrome, Neurodegeneration with brain iron accumulation, Pantothenate kinase-associated neurodegeneration
ATP13A2	2 / 12	kufor-rakeb syndrome, Neurodegeneration with brain iron accumulation
CHD6	2 / 12	Hallermanns syndrome, Hallervorden spatz syndrome
COASY	2 / 12	Hallervorden spatz syndrome, Neurodegeneration with brain iron accumulation
FA2H	2 / 12	hereditary spastic paraplegia 35, Neurodegeneration with brain iron accumulation
GJB3	2 / 12	Erythrokeratodermia variabilis, Greither disease
GJB4	2 / 12	Erythrokeratodermia variabilis, Greither disease
KDSR	2 / 12	Erythrokeratodermia variabilis, erythrokeratodermia variabilis et progressiva 4
PERP	2 / 12	Erythrokeratodermia variabilis, Greither disease
PLA2G6	2 / 12	Hallervorden spatz syndrome, Neurodegeneration with brain iron accumulation
WDR45	2 / 12	Hallervorden spatz syndrome, Neurodegeneration with brain iron accumulation

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 ⇵
Golgi Associated Vesicle Biogenesis AP1B1, AP1S1, FTL, FTH1	Reactome	4 / 56	28.6×	1.06e-5	3.53e-4 ✓ sig.
Gap junction assembly GJA1, GJB3, GJB4	Reactome	3 / 18	66.7×	1.12e-5	3.68e-4 ✓ sig.
Iron uptake and transport CP, FTL, FTH1	Reactome	3 / 28	42.9×	4.42e-5	1.15e-3 ✓ sig.
Ferroptosis CP, FTL, FTH1	KEGG	3 / 42	28.6×	1.51e-4	3.13e-3 ✓ sig.
Coenzyme A biosynthesis PANK2, COASY	Reactome	2 / 8	100×	1.67e-4	3.40e-3 ✓ sig.
Porphyrin metabolism CP, FTL, FTH1	KEGG	3 / 46	26.1×	1.99e-4	3.88e-3 ✓ sig.
Nef mediated downregulation of MHC class I complex cell surface expression AP1B1, AP1S1	Reactome	2 / 10	80.1×	2.68e-4	4.92e-3 ✓ sig.
Pantothenate and CoA biosynthesis PANK2, COASY	KEGG	2 / 21	38.1×	1.23e-3	1.58e-2 ✓ sig.
Retinoid metabolism disease events RBP4	Reactome	1 / 1	400×	2.50e-3	2.69e-2 ✓ sig.
Lysosome Vesicle Biogenesis AP1B1, AP1S1	Reactome	2 / 35	22.9×	3.41e-3	3.37e-2 ✓ sig.
Defective SLC40A1 causes hemochromatosis 4 (HFE4) (macrophages) CP	Reactome	1 / 2	200×	4.99e-3	4.37e-2 ✓ sig.
Defective CP causes aceruloplasminemia (ACERULOP) CP	Reactome	1 / 2	200×	4.99e-3	4.37e-2 ✓ sig.
Sphingolipid de novo biosynthesis KDSR, FA2H	Reactome	2 / 43	18.6×	5.11e-3	4.44e-2 ✓ sig.
COPI-independent Golgi-to-ER retrograde traffic RAB3GAP1, PLA2G6	Reactome	2 / 51	15.7×	7.13e-3	5.54e-2
Regulation of gap junction activity GJA1	Reactome	1 / 3	133×	7.48e-3	5.69e-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 ⇵
intracellular iron ion homeostasis CP, FTL, ATP13A2, FTH1	GO:0006879	4 / 71	35.1×	4.87e-6	2.94e-4 ✓ sig.
basolateral protein secretion AP1B1, AP1S1	GO:0110010	2 / 5	249×	2.48e-5	1.06e-3 ✓ sig.
coenzyme A biosynthetic process PANK2, COASY	GO:0015937	2 / 10	125×	1.11e-4	3.27e-3 ✓ sig.
glutamate secretion GJA1, BEST1	GO:0014047	2 / 11	113×	1.36e-4	3.80e-3 ✓ sig.
cell communication GJA1, GJB3, GJB4	GO:0007154	3 / 80	23.4×	2.82e-4	6.43e-3 ✓ sig.
bone remodeling GJA1, EPHA2	GO:0046849	2 / 18	69.2×	3.75e-4	7.82e-3 ✓ sig.
melanosome assembly AP1B1, AP1S1	GO:1903232	2 / 19	65.6×	4.19e-4	8.50e-3 ✓ sig.
positive regulation of autophagosome assembly RAB3GAP1, WDR45	GO:2000786	2 / 23	54.2×	6.17e-4	1.11e-2 ✓ sig.
detection of light stimulus involved in visual perception RBP4, BEST1	GO:0050908	2 / 24	51.9×	6.73e-4	1.16e-2 ✓ sig.
platelet dense granule organization AP1B1, AP1S1	GO:0060155	2 / 25	49.8×	7.30e-4	1.23e-2 ✓ sig.
iron ion transport FTL, FTH1	GO:0006826	2 / 31	40.2×	1.13e-3	1.62e-2 ✓ sig.
positive regulation of atrial cardiac muscle cell action potential TRPM4	GO:1903949	1 / 1	623×	1.61e-3	1.98e-2 ✓ sig.
positive regulation of regulation of vascular associated smooth muscle cell membrane depolarization TRPM4	GO:1904199	1 / 1	623×	1.61e-3	1.98e-2 ✓ sig.
notochord cell development EPHA2	GO:0060035	1 / 1	623×	1.61e-3	1.98e-2 ✓ sig.
microtubule-based transport GJA1	GO:0099111	1 / 1	623×	1.61e-3	1.98e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵	Disease B ⇵	Similarity score ⇵	Shared genes ⇵	P-value ⇵	FDR q-value ⇵
Hallervorden spatz syndrome	Neurodegeneration with brain iron accumulation	0.294	5	5.83e-15	8.78e-14 ✓ sig.
Erythrokeratodermia variabilis	Greither disease	0.364	4	8.97e-14	1.23e-12 ✓ sig.
Hallermanns syndrome	Hallervorden spatz syndrome	0.250	2	1.77e-7	1.25e-6 ✓ sig.
Hallermanns syndrome	Palmoplantar keratoderma with congenital alopecia	0.333	1	1.30e-4	3.90e-4 ✓ sig.
Greither disease	Palmoplantar keratoderma with congenital alopecia	0.200	1	2.60e-4	6.40e-4 ✓ sig.
Bilateral microphthalmos	Palmoplantar keratoderma with congenital alopecia	0.167	1	3.25e-4	7.58e-4 ✓ sig.
Hallervorden spatz syndrome	neurodegeneration with brain iron accumulation 4	0.125	1	4.55e-4	9.55e-4 ✓ sig.
Hallervorden spatz syndrome	Pantothenate kinase-associated neurodegeneration	0.125	1	4.55e-4	9.55e-4 ✓ sig.
Hallervorden spatz syndrome	Palmoplantar keratoderma with congenital alopecia	0.125	1	4.55e-4	9.55e-4 ✓ sig.
Greither disease	Hallermanns syndrome	0.167	1	5.19e-4	1.04e-3 ✓ sig.
Bilateral microphthalmos	Hallermanns syndrome	0.143	1	6.49e-4	1.22e-3 ✓ sig.
Erythrokeratodermia variabilis	erythrokeratodermia variabilis et progressiva 4	0.091	1	6.49e-4	1.22e-3 ✓ sig.
Erythrokeratodermia variabilis	Palmoplantar keratoderma with congenital alopecia	0.091	1	6.49e-4	1.22e-3 ✓ sig.
hereditary spastic paraplegia 35	Neurodegeneration with brain iron accumulation	0.067	1	9.09e-4	1.56e-3 ✓ sig.
kufor-rakeb syndrome	Neurodegeneration with brain iron accumulation	0.067	1	9.09e-4	1.56e-3 ✓ sig.
Neurodegeneration with brain iron accumulation	neurodegeneration with brain iron accumulation 4	0.067	1	9.09e-4	1.56e-3 ✓ sig.
Neurodegeneration with brain iron accumulation	Pantothenate kinase-associated neurodegeneration	0.067	1	9.09e-4	1.56e-3 ✓ sig.

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