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 155

9 diseases · 19 shared-gene connections
9 Diseases
25 Unique genes
0.191 Avg. similarity score
Neural tube defects, folate-sensitive Most-connected disease (7 links)
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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.

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

Disease ⇵ Connections in cluster ⇵ Significant partners ⇵ Curated genes ⇵
Neural tube defects, folate-sensitive 7 7 4
Homocystinuria with megaloblastic anemia 6 6 4
Hyperhomocysteinemia 5 5 13
Anencephaly 4 4 9
Aprosencephaly 4 4 4
methylcobalamin deficiency type cblE 4 4 1
methylcobalamin deficiency type cblG 4 4 1
Malnutrition 3 3 3
Advanced sleep phase syndrome 1 1 3

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

Gene ⇵ Member diseases ⇵ Linked diseases
MTRR 6 / 9 Anencephaly, Aprosencephaly, Homocystinuria with megaloblastic anemia, Hyperhomocysteinemia and 2 more
MTR 5 / 9 Homocystinuria with megaloblastic anemia, Hyperhomocysteinemia, Malnutrition, methylcobalamin deficiency type cblG and 1 more
MTHFR 4 / 9 Anencephaly, Hyperhomocysteinemia, Malnutrition, Neural tube defects, folate-sensitive
CBS 2 / 9 Hyperhomocysteinemia, Malnutrition
NUAK2 2 / 9 Anencephaly, Aprosencephaly
PER3 2 / 9 Advanced sleep phase syndrome, Homocystinuria with megaloblastic anemia
RPGRIP1L 2 / 9 Anencephaly, Aprosencephaly
TRIM36 2 / 9 Anencephaly, Aprosencephaly
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
MTHFR, MTR, CBS, GNMT, MTHFD1
 KEGG 5 / 38 63.2× 1.22e-8 1.04e-6 ✓ sig.
Folate transport and metabolism
MTHFR, MTR, SLC46A1, MTHFD1
 KEGG 4 / 31 62.0× 4.42e-7 2.41e-5 ✓ sig.
Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE
MTRR, MTR
 Reactome 2 / 2 480× 4.16e-6 1.63e-4 ✓ sig.
Defective MTR causes methylmalonic aciduria and homocystinuria type cblG
MTRR, MTR
 Reactome 2 / 2 480× 4.16e-6 1.63e-4 ✓ sig.
Metabolism of folate and pterines
MTHFR, SLC46A1, MTHFD1
 Reactome 3 / 17 84.8× 5.32e-6 1.99e-4 ✓ sig.
Cobalamin transport and metabolism
MTRR, MMADHC, MTR
 KEGG 3 / 18 80.1× 6.37e-6 2.29e-4 ✓ sig.
Cobalamin (Cbl, vitamin B12) transport and metabolism
MTRR, MMADHC, MTR
 Reactome 3 / 21 68.6× 1.03e-5 3.45e-4 ✓ sig.
Antifolate resistance
MTHFR, SLC46A1, TNF
 KEGG 3 / 30 48.0× 3.12e-5 8.62e-4 ✓ sig.
Circadian rhythm
CSNK1D, PER2, PER3
 KEGG 3 / 34 42.4× 4.57e-5 1.19e-3 ✓ sig.
Sulfur amino acid metabolism
MTRR, MTR
 Reactome 2 / 6 160× 6.21e-5 1.52e-3 ✓ sig.
Cysteine and methionine metabolism
MTR, CBS, GNMT
 KEGG 3 / 52 27.7× 1.65e-4 3.35e-3 ✓ sig.
Legionellosis
CASP1, PYCARD, TNF
 KEGG 3 / 56 25.7× 2.05e-4 3.98e-3 ✓ sig.
Methylation
MTRR, MTR
 Reactome 2 / 14 68.6× 3.73e-4 6.34e-3 ✓ sig.
The NLRP3 inflammasome
CASP1, PYCARD
 Reactome 2 / 15 64.1× 4.30e-4 7.08e-3 ✓ sig.
Pertussis
CASP1, PYCARD, TNF
 KEGG 3 / 78 18.5× 5.47e-4 8.53e-3 ✓ sig.

Enriched GO Terms (Biological Process, a second line of biological evidence)

GO term ⇵ GO ID ⇵ Overlap genes ⇵ Fold enrichment ⇵ P-value ⇵ FDR q-value ⇵
homocysteine metabolic process
MTHFR, MTRR, MTR, CBS
 GO:0050667 4 / 10 299× 5.20e-10 1.25e-7 ✓ sig.
methionine biosynthetic process
MTHFR, MTRR, MTR, MTHFD1
 GO:0009086 4 / 11 272× 8.17e-10 1.87e-7 ✓ sig.
methionine metabolic process
MTHFR, GNMT, MTHFD1
 GO:0006555 3 / 6 374× 4.22e-8 5.86e-6 ✓ sig.
cobalamin metabolic process
MTRR, MMADHC, MTR
 GO:0009235 3 / 9 249× 1.77e-7 1.95e-5 ✓ sig.
non-motile cilium assembly
CSNK1D, CC2D2A, RPGRIP1L, VANGL2
 GO:1905515 4 / 57 52.5× 9.38e-7 7.89e-5 ✓ sig.
folic acid metabolic process
MTRR, SLC46A1, MTHFD1
 GO:0046655 3 / 15 149× 9.52e-7 7.98e-5 ✓ sig.
neural tube closure
CC2D2A, MTHFR, VANGL2, MTHFD1
 GO:0001843 4 / 85 35.2× 4.69e-6 2.85e-4 ✓ sig.
amino acid biosynthetic process
MTRR, MTR, CBS
 GO:0008652 3 / 27 83.1× 6.06e-6 3.50e-4 ✓ sig.
S-adenosylmethionine metabolic process
MTHFR, GNMT
 GO:0046500 2 / 4 374× 1.03e-5 5.33e-4 ✓ sig.
homocysteine catabolic process
MTRR, CBS
 GO:0043418 2 / 4 374× 1.03e-5 5.33e-4 ✓ sig.
serine family amino acid metabolic process
CBS, MTHFD1
 GO:0009069 2 / 4 374× 1.03e-5 5.33e-4 ✓ sig.
transsulfuration
CBS, MTHFD1
 GO:0019346 2 / 5 299× 1.71e-5 7.95e-4 ✓ sig.
positive regulation of extrinsic apoptotic signaling pathway
AGT, PYCARD, TNF
 GO:2001238 3 / 38 59.0× 1.73e-5 8.00e-4 ✓ sig.
positive regulation of inflammatory response
AGT, CASP1, PYCARD, TNF
 GO:0050729 4 / 122 24.5× 1.97e-5 8.86e-4 ✓ sig.
response to folic acid
MTHFR, CBS
 GO:0051593 2 / 8 187× 4.79e-5 1.74e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Anencephaly Aprosencephaly 0.400 4 5.38e-14 7.53e-13 ✓ sig.
Hyperhomocysteinemia Malnutrition 0.214 3 4.70e-10 4.65e-9 ✓ sig.
Hyperhomocysteinemia Neural tube defects, folate-sensitive 0.200 3 1.88e-9 1.75e-8 ✓ sig.
Malnutrition Neural tube defects, folate-sensitive 0.333 2 1.52e-7 1.09e-6 ✓ sig.
Homocystinuria with megaloblastic anemia Neural tube defects, folate-sensitive 0.286 2 3.04e-7 2.06e-6 ✓ sig.
Anencephaly Neural tube defects, folate-sensitive 0.167 2 1.82e-6 1.08e-5 ✓ sig.
Homocystinuria with megaloblastic anemia Hyperhomocysteinemia 0.125 2 3.94e-6 2.20e-5 ✓ sig.
Anencephaly Hyperhomocysteinemia 0.095 2 2.36e-5 1.18e-4 ✓ sig.
Malnutrition methylcobalamin deficiency type cblG 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Aprosencephaly methylcobalamin deficiency type cblE 0.200 1 2.60e-4 6.40e-4 ✓ sig.
methylcobalamin deficiency type cblG Neural tube defects, folate-sensitive 0.200 1 2.60e-4 6.40e-4 ✓ sig.
methylcobalamin deficiency type cblE Neural tube defects, folate-sensitive 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Homocystinuria with megaloblastic anemia methylcobalamin deficiency type cblG 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Homocystinuria with megaloblastic anemia methylcobalamin deficiency type cblE 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Anencephaly methylcobalamin deficiency type cblE 0.100 1 5.84e-4 1.14e-3 ✓ sig.
Advanced sleep phase syndrome Homocystinuria with megaloblastic anemia 0.143 1 7.79e-4 1.39e-3 ✓ sig.
Hyperhomocysteinemia methylcobalamin deficiency type cblG 0.071 1 8.44e-4 1.48e-3 ✓ sig.
Aprosencephaly Neural tube defects, folate-sensitive 0.125 1 1.04e-3 1.72e-3 ✓ sig.
Aprosencephaly Homocystinuria with megaloblastic anemia 0.125 1 1.04e-3 1.72e-3 ✓ sig.