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 34

17 diseases · 35 shared-gene connections
17 Diseases
68 Unique genes
0.169 Avg. similarity score
Neural tube defects, folate-sensitive Most-connected disease (9 links)
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Disease Searched: Methylmalonic acidemia 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 9 9 4
Intracellular cobalamin metabolism disorder 8 8 9
Homocystinuria with megaloblastic anemia 7 7 4
Hyperhomocysteinemia 6 6 13
Methylmalonic acidemia 6 6 27
methylcobalamin deficiency type cblG 5 5 1
Anencephaly 4 4 9
Aprosencephaly 4 4 4
Malnutrition 4 4 3
methylcobalamin deficiency type cblE 4 4 1
Cobalamin c disease 3 3 7
methylmalonic acidemia with homocystinuria, type cblJ 3 3 1
Hematologic disease 2 2 18
methylmalonic aciduria and homocystinuria 2 2 2
Advanced sleep phase syndrome 1 1 3
Alpha-mannosidosis 1 1 1
methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
MTR 7 / 17 Hematologic disease, Homocystinuria with megaloblastic anemia, Hyperhomocysteinemia, Intracellular cobalamin metabolism disorder and 3 more
MTRR 7 / 17 Anencephaly, Aprosencephaly, Homocystinuria with megaloblastic anemia, Hyperhomocysteinemia and 3 more
MTHFR 5 / 17 Anencephaly, Hematologic disease, Hyperhomocysteinemia, Malnutrition and 1 more
ABCD4 4 / 17 Cobalamin c disease, Intracellular cobalamin metabolism disorder, Methylmalonic acidemia, methylmalonic acidemia with homocystinuria, type cblJ
MMADHC 4 / 17 Cobalamin c disease, Homocystinuria with megaloblastic anemia, Intracellular cobalamin metabolism disorder, Methylmalonic acidemia
HCFC1 3 / 17 Cobalamin c disease, Intracellular cobalamin metabolism disorder, Methylmalonic acidemia
LMBRD1 3 / 17 Cobalamin c disease, Intracellular cobalamin metabolism disorder, Methylmalonic acidemia
MMACHC 3 / 17 Cobalamin c disease, Intracellular cobalamin metabolism disorder, Methylmalonic acidemia
THAP11 3 / 17 Intracellular cobalamin metabolism disorder, Methylmalonic acidemia, methylmalonic aciduria and homocystinuria
ZNF143 3 / 17 Intracellular cobalamin metabolism disorder, Methylmalonic acidemia, methylmalonic aciduria and homocystinuria
CBS 2 / 17 Hyperhomocysteinemia, Malnutrition
MAN2B1 2 / 17 Alpha-mannosidosis, Methylmalonic acidemia
MCEE 2 / 17 Methylmalonic acidemia, methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency
NUAK2 2 / 17 Anencephaly, Aprosencephaly
PER3 2 / 17 Advanced sleep phase syndrome, Homocystinuria with megaloblastic anemia
PRDX1 2 / 17 Cobalamin c disease, Methylmalonic acidemia
RPGRIP1L 2 / 17 Anencephaly, Aprosencephaly
TRIM36 2 / 17 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 ⇵
Cobalamin transport and metabolism
MTRR, ABCD4, HCFC1, LMBRD1, MMACHC, MMADHC, PRDX1, MTR, THAP11, ZNF143, MMAA, MMAB
 KEGG 14 / 18 137× 2.51e-29 6.32e-26 ✓ sig.
Cobalamin (Cbl, vitamin B12) transport and metabolism
MTRR, ABCD4, LMBRD1, MMACHC, MMADHC, MTR, MMAA, MMAB, MMUT, CD320
 Reactome 10 / 21 84.1× 5.70e-18 2.91e-15 ✓ sig.
Propionyl-CoA catabolism
MCEE, MMAA, MMUT
 Reactome 3 / 5 106× 1.72e-6 7.80e-5 ✓ sig.
One carbon pool by folate
MTHFR, MTR, CBS, GNMT, MTHFD1
 KEGG 5 / 38 23.2× 2.18e-6 9.57e-5 ✓ sig.
Vitamin digestion and absorption
ABCD4, LMBRD1, MMACHC, SLC46A1
 KEGG 4 / 26 27.2× 1.28e-5 4.19e-4 ✓ sig.
Legionellosis
HBS1L, CASP1, PYCARD, TNF, CYCS
 KEGG 5 / 56 15.8× 1.53e-5 4.86e-4 ✓ sig.
Folate transport and metabolism
MTHFR, MTR, SLC46A1, MTHFD1
 KEGG 4 / 31 22.8× 2.64e-5 7.66e-4 ✓ sig.
Defective MMAA causes methylmalonic aciduria type cblA
MMAA, MMUT
 Reactome 2 / 2 177× 3.16e-5 8.85e-4 ✓ sig.
Defective MUT causes methylmalonic aciduria mut type
MMAA, MMUT
 Reactome 2 / 2 177× 3.16e-5 8.85e-4 ✓ sig.
Defective MMADHC causes methylmalonic aciduria and homocystinuria type cblD
MMACHC, MMADHC
 Reactome 2 / 2 177× 3.16e-5 8.85e-4 ✓ sig.
Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE
MTRR, MTR
 Reactome 2 / 2 177× 3.16e-5 8.85e-4 ✓ sig.
Defective MTR causes methylmalonic aciduria and homocystinuria type cblG
MTRR, MTR
 Reactome 2 / 2 177× 3.16e-5 8.85e-4 ✓ sig.
Detoxification of Reactive Oxygen Species
PRDX1, GSTP1, CYCS, SOD2
 Reactome 4 / 34 20.8× 3.84e-5 1.04e-3 ✓ sig.
Influenza A
JAK2, FAS, NUP98, CASP1, PYCARD, TNF, CYCS
 KEGG 7 / 173 7.1× 5.27e-5 1.35e-3 ✓ sig.
Peroxisome
ABCD4, PRDX1, MVK, SOD2, PEX16
 KEGG 5 / 83 10.6× 1.03e-4 2.33e-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 ⇵
cobalamin metabolic process
MTRR, ABCD4, MMACHC, MMADHC, MTR, MMAA, MMAB
 GO:0009235 7 / 9 214× 2.20e-16 1.91e-13 ✓ sig.
homocysteine metabolic process
MTHFR, MTRR, MTR, CBS, MMUT
 GO:0050667 5 / 10 137× 1.36e-10 3.78e-8 ✓ sig.
methionine biosynthetic process
MTHFR, MTRR, MTR, MTHFD1
 GO:0009086 4 / 11 99.9× 5.19e-8 7.00e-6 ✓ sig.
methionine metabolic process
MTHFR, GNMT, MTHFD1
 GO:0006555 3 / 6 137× 9.15e-7 7.77e-5 ✓ sig.
regulation of stress-activated MAPK cascade
PRDX1, FAS, GSTP1
 GO:0032872 3 / 10 82.4× 5.43e-6 3.27e-4 ✓ sig.
response to nutrient levels
ALAD, GSTP1, CBS, TNF, SOD2
 GO:0031667 5 / 79 17.4× 1.01e-5 5.33e-4 ✓ sig.
folic acid metabolic process
MTRR, SLC46A1, MTHFD1
 GO:0046655 3 / 15 55.0× 2.03e-5 9.24e-4 ✓ sig.
response to reactive oxygen species
PRDX1, GSTP1, SOD2
 GO:0000302 3 / 20 41.2× 5.03e-5 1.84e-3 ✓ sig.
non-motile cilium assembly
CSNK1D, CC2D2A, RPGRIP1L, VANGL2
 GO:1905515 4 / 57 19.3× 5.48e-5 1.96e-3 ✓ sig.
tumor necrosis factor-mediated signaling pathway
JAK2, FAS, PYCARD, TNF
 GO:0033209 4 / 60 18.3× 6.71e-5 2.29e-3 ✓ sig.
response to amino acid
MTHFR, ALAD, GSTP1
 GO:0043200 3 / 22 37.5× 6.75e-5 2.30e-3 ✓ sig.
response to L-ascorbic acid
GSTP1, SOD2
 GO:0033591 2 / 4 137× 7.79e-5 2.57e-3 ✓ sig.
response to isolation stress
TNF, SOD2
 GO:0035900 2 / 4 137× 7.79e-5 2.57e-3 ✓ sig.
S-adenosylmethionine metabolic process
MTHFR, GNMT
 GO:0046500 2 / 4 137× 7.79e-5 2.57e-3 ✓ sig.
homocysteine catabolic process
MTRR, CBS
 GO:0043418 2 / 4 137× 7.79e-5 2.57e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Intracellular cobalamin metabolism disorder Methylmalonic acidemia 0.233 7 7.84e-19 1.41e-17 ✓ sig.
Cobalamin c disease Methylmalonic acidemia 0.207 6 1.12e-16 1.80e-15 ✓ sig.
Cobalamin c disease Intracellular cobalamin metabolism disorder 0.417 5 3.67e-16 5.69e-15 ✓ sig.
Anencephaly Aprosencephaly 0.400 4 5.38e-14 7.14e-13 ✓ sig.
Hyperhomocysteinemia Malnutrition 0.214 3 4.70e-10 4.41e-9 ✓ sig.
Homocystinuria with megaloblastic anemia Intracellular cobalamin metabolism disorder 0.273 3 5.52e-10 5.14e-9 ✓ sig.
Hyperhomocysteinemia Neural tube defects, folate-sensitive 0.200 3 1.88e-9 1.66e-8 ✓ sig.
Malnutrition Neural tube defects, folate-sensitive 0.333 2 1.52e-7 1.03e-6 ✓ sig.
Homocystinuria with megaloblastic anemia Neural tube defects, folate-sensitive 0.286 2 3.04e-7 1.96e-6 ✓ sig.
Intracellular cobalamin metabolism disorder methylmalonic aciduria and homocystinuria 0.200 2 3.04e-7 1.96e-6 ✓ sig.
Anencephaly Neural tube defects, folate-sensitive 0.167 2 1.82e-6 1.02e-5 ✓ sig.
Intracellular cobalamin metabolism disorder Neural tube defects, folate-sensitive 0.167 2 1.82e-6 1.02e-5 ✓ sig.
Methylmalonic acidemia methylmalonic aciduria and homocystinuria 0.071 2 2.96e-6 1.61e-5 ✓ sig.
Hematologic disease Malnutrition 0.100 2 3.87e-6 2.05e-5 ✓ sig.
Homocystinuria with megaloblastic anemia Hyperhomocysteinemia 0.125 2 3.94e-6 2.09e-5 ✓ sig.
Hematologic disease Neural tube defects, folate-sensitive 0.095 2 7.73e-6 3.91e-5 ✓ sig.
Anencephaly Hyperhomocysteinemia 0.095 2 2.36e-5 1.11e-4 ✓ sig.
Hyperhomocysteinemia Intracellular cobalamin metabolism disorder 0.095 2 2.36e-5 1.11e-4 ✓ sig.
Malnutrition methylcobalamin deficiency type cblG 0.250 1 1.95e-4 5.32e-4 ✓ sig.
Homocystinuria with megaloblastic anemia methylcobalamin deficiency type cblE 0.200 1 2.60e-4 6.48e-4 ✓ sig.
Homocystinuria with megaloblastic anemia methylcobalamin deficiency type cblG 0.200 1 2.60e-4 6.48e-4 ✓ sig.
methylcobalamin deficiency type cblG Neural tube defects, folate-sensitive 0.200 1 2.60e-4 6.48e-4 ✓ sig.
Aprosencephaly methylcobalamin deficiency type cblE 0.200 1 2.60e-4 6.48e-4 ✓ sig.
methylcobalamin deficiency type cblE Neural tube defects, folate-sensitive 0.200 1 2.60e-4 6.48e-4 ✓ sig.
Cobalamin c disease methylmalonic acidemia with homocystinuria, type cblJ 0.125 1 4.55e-4 9.70e-4 ✓ sig.
Intracellular cobalamin metabolism disorder methylcobalamin deficiency type cblG 0.100 1 5.84e-4 1.15e-3 ✓ sig.
Intracellular cobalamin metabolism disorder methylmalonic acidemia with homocystinuria, type cblJ 0.100 1 5.84e-4 1.15e-3 ✓ sig.
Anencephaly methylcobalamin deficiency type cblE 0.100 1 5.84e-4 1.15e-3 ✓ sig.
Advanced sleep phase syndrome Homocystinuria with megaloblastic anemia 0.143 1 7.79e-4 1.40e-3 ✓ sig.
Hyperhomocysteinemia methylcobalamin deficiency type cblG 0.071 1 8.44e-4 1.50e-3 ✓ sig.
Aprosencephaly Neural tube defects, folate-sensitive 0.125 1 1.04e-3 1.74e-3 ✓ sig.
Aprosencephaly Homocystinuria with megaloblastic anemia 0.125 1 1.04e-3 1.74e-3 ✓ sig.
Methylmalonic acidemia methylmalonic acidemia with homocystinuria, type cblJ 0.036 1 1.75e-3 2.61e-3 ✓ sig.
Methylmalonic acidemia methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency 0.036 1 1.75e-3 2.61e-3 ✓ sig.
Alpha-mannosidosis Methylmalonic acidemia 0.036 1 1.75e-3 2.61e-3 ✓ sig.