Disease Clusters?

Groups of diseases that share a large number of curated genes with each other, computed via label propagation over the shared-gene similarity graph. See also Shared-Gene Disease Pairs for pairwise comparisons.

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Cluster 232

7 diseases · 12 shared-gene connections
7 Diseases
4 Unique genes
0.317 Avg. similarity score
Hepatic methionine adenosyltransferase deficiency Most-connected disease (5 links)
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Disease Searched: methionine adenosyltransferase deficiency 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.

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

Disease ⇵ Connections in cluster ⇵ Significant partners ⇵ Curated genes ⇵
Hepatic methionine adenosyltransferase deficiency 5 5 3
S-adenosylhomocysteine hydrolase deficiency 5 5 3
Sulfur amino acid metabolism disorder 5 5 3
Glycine n-methyltransferase deficiency 3 3 1
hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase 3 3 1
methionine adenosyltransferase deficiency 2 2 1
Adenosine kinase deficiency 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
AHCY 4 / 7 Hepatic methionine adenosyltransferase deficiency, hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase, S-adenosylhomocysteine hydrolase deficiency, Sulfur amino acid metabolism disorder
GNMT 4 / 7 Glycine n-methyltransferase deficiency, Hepatic methionine adenosyltransferase deficiency, S-adenosylhomocysteine hydrolase deficiency, Sulfur amino acid metabolism disorder
MAT1A 3 / 7 Hepatic methionine adenosyltransferase deficiency, methionine adenosyltransferase deficiency, S-adenosylhomocysteine hydrolase deficiency
ADK 2 / 7 Adenosine kinase deficiency, Sulfur amino acid metabolism disorder
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 ⇵
One carbon pool by folate
AHCY, GNMT, MAT1A
 KEGG 3 / 38 237× 1.17e-7 7.48e-6 ✓ sig.
Cysteine and methionine metabolism
AHCY, GNMT, MAT1A
 KEGG 3 / 52 173× 3.05e-7 1.74e-5 ✓ sig.
Sulfur amino acid metabolism
AHCY, MAT1A
 Reactome 2 / 6 1,001× 1.25e-6 5.89e-5 ✓ sig.
Methylation
AHCY, MAT1A
 Reactome 2 / 14 429× 7.56e-6 2.72e-4 ✓ sig.
Metabolic pathways
ADK, AHCY, GNMT, MAT1A
 KEGG 4 / 1,563 7.7× 2.86e-4 5.24e-3 ✓ sig.
Defective AHCY causes Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (HMAHCHD)
AHCY
 Reactome 1 / 1 3,003× 3.33e-4 5.91e-3 ✓ sig.
Defective MAT1A causes Methionine adenosyltransferase deficiency (MATD)
MAT1A
 Reactome 1 / 1 3,003× 3.33e-4 5.91e-3 ✓ sig.
Metabolism of ingested SeMet, Sec, MeSec into H2Se
MAT1A
 Reactome 1 / 2 1,501× 6.66e-4 1.02e-2 ✓ sig.
Purine salvage
ADK
 Reactome 1 / 13 231× 4.32e-3 4.04e-2 ✓ sig.
Glyoxylate metabolism and glycine degradation
GNMT
 Reactome 1 / 28 107× 9.29e-3 6.69e-2
Glycine, serine and threonine metabolism
GNMT
 KEGG 1 / 40 75.1× 1.33e-2 8.31e-2
Biosynthesis of amino acids
MAT1A
 KEGG 1 / 75 40.0× 2.47e-2 1.20e-1
Nucleotide metabolism
ADK
 KEGG 1 / 85 35.3× 2.80e-2 1.28e-1
Purine metabolism
ADK
 KEGG 1 / 128 23.5× 4.20e-2 1.59e-1
Biosynthesis of cofactors
MAT1A
 KEGG 1 / 154 19.5× 5.03e-2 1.75e-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 ⇵
one-carbon metabolic process
AHCY, GNMT, MAT1A
 GO:0006730 3 / 21 667× 4.89e-9 8.91e-7 ✓ sig.
protein homotetramerization
GNMT, MAT1A
 GO:0051289 2 / 66 142× 7.34e-5 2.45e-3 ✓ sig.
dATP biosynthetic process
ADK
 GO:0006175 1 / 1 4,672× 2.14e-4 5.39e-3 ✓ sig.
L-methionine catabolic process
MAT1A
 GO:0009087 1 / 1 4,672× 2.14e-4 5.39e-3 ✓ sig.
sarcosine metabolic process
GNMT
 GO:1901052 1 / 1 4,672× 2.14e-4 5.39e-3 ✓ sig.
S-adenosylhomocysteine metabolic process
GNMT
 GO:0046498 1 / 2 2,336× 4.28e-4 8.77e-3 ✓ sig.
dAMP salvage
ADK
 GO:0106383 1 / 3 1,557× 6.42e-4 1.15e-2 ✓ sig.
ribonucleoside monophosphate biosynthetic process
ADK
 GO:0009156 1 / 4 1,168× 8.56e-4 1.39e-2 ✓ sig.
S-adenosylmethionine cycle
AHCY
 GO:0033353 1 / 4 1,168× 8.56e-4 1.39e-2 ✓ sig.
S-adenosylmethionine biosynthetic process
MAT1A
 GO:0006556 1 / 4 1,168× 8.56e-4 1.39e-2 ✓ sig.
S-adenosylmethionine metabolic process
GNMT
 GO:0046500 1 / 4 1,168× 8.56e-4 1.39e-2 ✓ sig.
GMP salvage
ADK
 GO:0032263 1 / 5 934× 1.07e-3 1.60e-2 ✓ sig.
AMP salvage
ADK
 GO:0044209 1 / 6 779× 1.28e-3 1.79e-2 ✓ sig.
methionine metabolic process
GNMT
 GO:0006555 1 / 6 779× 1.28e-3 1.79e-2 ✓ sig.
purine nucleobase metabolic process
ADK
 GO:0006144 1 / 7 667× 1.50e-3 1.95e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hepatic methionine adenosyltransferase deficiency S-adenosylhomocysteine hydrolase deficiency 0.750 3 1.64e-12 1.93e-11 ✓ sig.
Hepatic methionine adenosyltransferase deficiency Sulfur amino acid metabolism disorder 0.400 2 7.59e-8 5.43e-7 ✓ sig.
S-adenosylhomocysteine hydrolase deficiency Sulfur amino acid metabolism disorder 0.400 2 7.59e-8 5.43e-7 ✓ sig.
Adenosine kinase deficiency Sulfur amino acid metabolism disorder 0.250 1 1.95e-4 5.32e-4 ✓ sig.
Glycine n-methyltransferase deficiency S-adenosylhomocysteine hydrolase deficiency 0.250 1 1.95e-4 5.32e-4 ✓ sig.
Glycine n-methyltransferase deficiency Sulfur amino acid metabolism disorder 0.250 1 1.95e-4 5.32e-4 ✓ sig.
Glycine n-methyltransferase deficiency Hepatic methionine adenosyltransferase deficiency 0.250 1 1.95e-4 5.32e-4 ✓ sig.
Hepatic methionine adenosyltransferase deficiency hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase 0.250 1 1.95e-4 5.32e-4 ✓ sig.
Hepatic methionine adenosyltransferase deficiency methionine adenosyltransferase deficiency 0.250 1 1.95e-4 5.32e-4 ✓ sig.
hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase S-adenosylhomocysteine hydrolase deficiency 0.250 1 1.95e-4 5.32e-4 ✓ sig.
hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase Sulfur amino acid metabolism disorder 0.250 1 1.95e-4 5.32e-4 ✓ sig.
methionine adenosyltransferase deficiency S-adenosylhomocysteine hydrolase deficiency 0.250 1 1.95e-4 5.32e-4 ✓ sig.