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 58

15 diseases · 43 shared-gene connections
15 Diseases
164 Unique genes
0.468 Avg. similarity score
Growth hormone deficiency Most-connected disease (10 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 ⇵
Growth hormone deficiency 10 10 34
Kallmann syndrome 9 9 38
Panhypopituitarism 9 9 43
Pituitary short stature 8 8 34
Sheehan syndrome 8 8 34
Hypogonadism 7 7 76
Hypogonadotropic hypogonadism 7 7 47
Hypopituitarism 7 7 46
Pituitary stalk interruption syndrome 7 7 31
Pituitary dwarfism 6 6 44
hypogonadotropic hypogonadism 4 with or without anosmia 4 4 1
Brody myopathy 1 1 2
Cohen syndrome 1 1 1
GPR161-related medulloblastoma predisposition 1 1 1
amyotrophic lateral sclerosis type 15 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
KISS1R 10 / 15 Growth hormone deficiency, Hypogonadism, Hypogonadotropic hypogonadism, Hypopituitarism and 6 more
CHD7 9 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 5 more
GNRH1 9 / 15 Growth hormone deficiency, Hypogonadism, Hypogonadotropic hypogonadism, Hypopituitarism and 5 more
GNRHR 9 / 15 Growth hormone deficiency, Hypogonadism, Hypogonadotropic hypogonadism, Hypopituitarism and 5 more
IL17RD 9 / 15 Growth hormone deficiency, Hypogonadism, Hypogonadotropic hypogonadism, Hypopituitarism and 5 more
NSMF 9 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 5 more
PROK2 9 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, hypogonadotropic hypogonadism 4 with or without anosmia, Hypopituitarism and 5 more
PROKR2 9 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 5 more
TAC3 9 / 15 Growth hormone deficiency, Hypogonadism, Hypogonadotropic hypogonadism, Hypopituitarism and 5 more
TACR3 9 / 15 Growth hormone deficiency, Hypogonadism, Hypogonadotropic hypogonadism, Hypopituitarism and 5 more
WDR11 9 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 5 more
ANOS1 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
AXL 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
BTK 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
CCDC141 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
DNA2 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
DUSP6 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
FEZF1 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
FGF17 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
FGF8 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
FGFR1 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
FLRT3 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
GH1 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
GHRHR 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
HS6ST1 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
KISS1 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
NDNF 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
NHLH2 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
SEMA3A 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
SEMA3E 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
SOX10 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
SPRY4 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
SRA1 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
TCF12 8 / 15 Growth hormone deficiency, Hypogonadotropic hypogonadism, Hypopituitarism, Kallmann syndrome and 4 more
PROP1 4 / 15 Hypogonadism, Hypopituitarism, Panhypopituitarism, Pituitary dwarfism
HESX1 3 / 15 Kallmann syndrome, Panhypopituitarism, Pituitary stalk interruption syndrome
ATP2A1 2 / 15 Brody myopathy, Hypogonadism
CYP17A1 2 / 15 Hypogonadism, Hypopituitarism
CYP19A1 2 / 15 Hypogonadism, Hypopituitarism
FSHB 2 / 15 Hypogonadism, Hypogonadotropic hypogonadism
GPR161 2 / 15 GPR161-related medulloblastoma predisposition, Pituitary stalk interruption syndrome
LHB 2 / 15 Hypogonadism, Hypogonadotropic hypogonadism
LHX4 2 / 15 Panhypopituitarism, Pituitary stalk interruption syndrome
PNPLA6 2 / 15 Hypogonadotropic hypogonadism, Kallmann syndrome
POU1F1 2 / 15 Panhypopituitarism, Pituitary dwarfism
PRL 2 / 15 Hypogonadism, Hypopituitarism
ROBO1 2 / 15 Hypopituitarism, Pituitary stalk interruption syndrome
SOX11 2 / 15 Hypogonadotropic hypogonadism, Pituitary stalk interruption syndrome
UBQLN2 2 / 15 amyotrophic lateral sclerosis type 15, Hypogonadism
VPS13B 2 / 15 Cohen syndrome, Pituitary stalk interruption syndrome
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 ⇵
Hormone ligand-binding receptors
FSHB, GNRH1, GNRHR, LHB, LHCGR
 Reactome 5 / 12 30.5× 3.27e-7 1.85e-5 ✓ sig.
Hormone signaling
FSHB, GNRH1, GNRHR, LEP, LEPR, LHB, PRL, GH1, GHRHR, GNAI2, GHR, CSHL1
 KEGG 13 / 219 4.3× 9.35e-6 3.17e-4 ✓ sig.
FGFR1c ligand binding and activation
ANOS1, FGF17, FGF8, FGFR1
 Reactome 4 / 12 24.4× 1.52e-5 4.77e-4 ✓ sig.
Neuroactive ligand-receptor interaction
FSHB, GNRH1, GNRHR, KISS1R, LEP, LEPR, LHB, PRL, TAC3, TACR3, GH1, GHRHR
 KEGG 16 / 370 3.2× 4.60e-5 1.19e-3 ✓ sig.
FGFR3b ligand binding and activation
FGF17, FGF8, FGFR3
 Reactome 3 / 7 31.4× 8.41e-5 1.95e-3 ✓ sig.
Downstream signaling of activated FGFR1
FGF17, FGF8, FGFR1, FLRT3
 Reactome 4 / 18 16.3× 8.83e-5 2.03e-3 ✓ sig.
Axon guidance
PLXNA3, SEMA3A, SEMA3E, SEMA3F, GNAI2, ROBO1, DCC, PTCH1, RAF1, SEMA5A
 KEGG 10 / 183 4.0× 2.04e-4 3.97e-3 ✓ sig.
Steroid hormone biosynthesis
AKR1C4, CYP17A1, CYP19A1, SRD5A2, UGT2B10, UGT2B15
 KEGG 6 / 63 7.0× 2.11e-4 4.08e-3 ✓ sig.
Androgen biosynthesis
CYP17A1, LHB, SRD5A2
 Reactome 3 / 11 20.0× 3.81e-4 6.45e-3 ✓ sig.
Signaling by activated point mutants of FGFR1
FGF17, FGF8, FGFR1
 Reactome 3 / 11 20.0× 3.81e-4 6.45e-3 ✓ sig.
Negative regulation of FGFR1 signaling
ANOS1, FGF17, FGF8, FGFR1
 Reactome 4 / 26 11.3× 3.96e-4 6.66e-3 ✓ sig.
Glycoprotein hormones
CGB3, FSHB, LHB
 Reactome 3 / 12 18.3× 5.02e-4 7.99e-3 ✓ sig.
Prolactin receptor signaling
PRL, GH1, GHR
 Reactome 3 / 12 18.3× 5.02e-4 7.99e-3 ✓ sig.
Signaling by activated point mutants of FGFR3
FGF17, FGF8, FGFR3
 Reactome 3 / 12 18.3× 5.02e-4 7.99e-3 ✓ sig.
FGFR3 mutant receptor activation
FGF17, FGF8, FGFR3
 Reactome 3 / 12 18.3× 5.02e-4 7.99e-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 ⇵
pituitary gland development
NR0B1, PROP1, HESX1, LHX3, SOX3, GLI2, PITX2, TBX19
 GO:0021983 8 / 30 30.4× 1.47e-10 4.06e-8 ✓ sig.
axon guidance
NOTCH3, OPHN1, ANOS1, FEZF1, FLRT3, PLXNA3, SEMA3A, SEMA3E, SEMA3F, ROBO1, DCC, OTX2
 GO:0007411 14 / 192 8.3× 1.56e-9 3.33e-7 ✓ sig.
negative chemotaxis
FLRT3, PLXNA3, SEMA3A, SEMA3E, SEMA3F, SEMA5A
 GO:0050919 6 / 40 17.1× 1.25e-6 9.92e-5 ✓ sig.
motor neuron axon guidance
FGF8, PLXNA3, SEMA3A, LHX3, LHX4
 GO:0008045 5 / 24 23.7× 1.82e-6 1.34e-4 ✓ sig.
hormone metabolic process
AKR1C4, CYP17A1, LEP, GHRHR, GHR
 GO:0042445 5 / 25 22.8× 2.26e-6 1.59e-4 ✓ sig.
somatotropin secreting cell differentiation
PROP1, LHX3, PITX2
 GO:0060126 3 / 4 85.5× 2.64e-6 1.79e-4 ✓ sig.
female gonad development
CYP19A1, BRCA2, FANCA, LHX9, LHCGR
 GO:0008585 5 / 27 21.1× 3.38e-6 2.20e-4 ✓ sig.
positive regulation of MAPK cascade
AR, LEP, FGF17, FGF8, FGFR1, GH1, ROBO1, GHR, CDON, FGFR3, RAF1
 GO:0043410 11 / 224 5.6× 4.73e-6 2.88e-4 ✓ sig.
positive regulation of cell differentiation
AR, SERPINF2, FGF8, FGFR1, GHR, ARID1B, SMARCA2
 GO:0045597 7 / 83 9.6× 8.37e-6 4.54e-4 ✓ sig.
male gonad development
AR, LHB, NR0B1, SRD5A2, NHLH2, FANCA, LHX9, LHCGR
 GO:0008584 8 / 117 7.8× 8.99e-6 4.81e-4 ✓ sig.
nervous system development
VPS13B, NR2F6, OPHN1, PROP1, ZC4H2, AXL, FEZF1, FGF17, NDNF, SEMA3A, SEMA3E, SOX11
 GO:0007399 18 / 631 3.3× 1.13e-5 5.74e-4 ✓ sig.
trigeminal nerve structural organization
PLXNA3, SEMA3A, SEMA3F
 GO:0021637 3 / 6 57.0× 1.30e-5 6.42e-4 ✓ sig.
gonadotrophin-releasing hormone neuronal migration to the hypothalamus
NDNF, PLXNA3, SEMA3E
 GO:0021828 3 / 6 57.0× 1.30e-5 6.42e-4 ✓ sig.
cell maturation
AXL, BTK, FGFR1, GHRHR, SOX10
 GO:0048469 5 / 37 15.4× 1.70e-5 7.91e-4 ✓ sig.
mammary gland development
CYP19A1, PRL, GHRHR, GLI2, PTCH1
 GO:0030879 5 / 37 15.4× 1.70e-5 7.91e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Pituitary short stature Sheehan syndrome 0.971 34 1.29e-104 1.66e-102 ✓ sig.
Growth hormone deficiency Pituitary short stature 0.971 34 1.29e-104 1.66e-102 ✓ sig.
Growth hormone deficiency Sheehan syndrome 0.971 34 1.29e-104 1.66e-102 ✓ sig.
Growth hormone deficiency Kallmann syndrome 0.872 34 9.56e-100 1.11e-97 ✓ sig.
Kallmann syndrome Sheehan syndrome 0.872 34 9.56e-100 1.11e-97 ✓ sig.
Kallmann syndrome Pituitary short stature 0.872 34 9.56e-100 1.11e-97 ✓ sig.
Growth hormone deficiency Panhypopituitarism 0.773 34 7.30e-96 7.85e-94 ✓ sig.
Panhypopituitarism Pituitary short stature 0.773 34 7.30e-96 7.85e-94 ✓ sig.
Panhypopituitarism Sheehan syndrome 0.773 34 7.30e-96 7.85e-94 ✓ sig.
Pituitary dwarfism Sheehan syndrome 0.756 34 3.21e-95 3.40e-93 ✓ sig.
Pituitary dwarfism Pituitary short stature 0.756 34 3.21e-95 3.40e-93 ✓ sig.
Growth hormone deficiency Pituitary dwarfism 0.756 34 3.21e-95 3.40e-93 ✓ sig.
Kallmann syndrome Panhypopituitarism 0.745 35 3.60e-95 3.78e-93 ✓ sig.
Panhypopituitarism Pituitary dwarfism 0.692 36 3.93e-94 4.05e-92 ✓ sig.
Growth hormone deficiency Hypopituitarism 0.723 34 5.04e-94 5.12e-92 ✓ sig.
Hypopituitarism Pituitary short stature 0.723 34 5.04e-94 5.12e-92 ✓ sig.
Hypopituitarism Sheehan syndrome 0.723 34 5.04e-94 5.12e-92 ✓ sig.
Growth hormone deficiency Hypogonadotropic hypogonadism 0.708 34 1.82e-93 1.81e-91 ✓ sig.
Hypogonadotropic hypogonadism Pituitary short stature 0.708 34 1.82e-93 1.81e-91 ✓ sig.
Hypogonadotropic hypogonadism Sheehan syndrome 0.708 34 1.82e-93 1.81e-91 ✓ sig.
Hypogonadotropic hypogonadism Kallmann syndrome 0.686 35 1.30e-92 1.26e-90 ✓ sig.
Kallmann syndrome Pituitary dwarfism 0.694 34 2.37e-90 2.26e-88 ✓ sig.
Hypopituitarism Kallmann syndrome 0.667 34 3.71e-89 3.45e-87 ✓ sig.
Hypopituitarism Panhypopituitarism 0.636 35 5.67e-89 5.25e-87 ✓ sig.
Hypogonadotropic hypogonadism Panhypopituitarism 0.596 34 1.02e-84 9.13e-83 ✓ sig.
Hypogonadism Hypopituitarism 0.089 10 1.64e-14 2.39e-13 ✓ sig.
Panhypopituitarism Pituitary stalk interruption syndrome 0.103 7 1.98e-12 2.44e-11 ✓ sig.
Hypogonadism Hypogonadotropic hypogonadism 0.069 8 6.50e-11 6.98e-10 ✓ sig.
Kallmann syndrome Pituitary stalk interruption syndrome 0.094 6 1.05e-10 1.10e-9 ✓ sig.
Hypopituitarism Pituitary stalk interruption syndrome 0.083 6 3.53e-10 3.54e-9 ✓ sig.
Hypogonadotropic hypogonadism Pituitary stalk interruption syndrome 0.082 6 4.04e-10 4.02e-9 ✓ sig.
Hypogonadism Panhypopituitarism 0.062 7 1.50e-9 1.42e-8 ✓ sig.
Hypogonadism Pituitary dwarfism 0.061 7 1.78e-9 1.67e-8 ✓ sig.
Growth hormone deficiency Pituitary stalk interruption syndrome 0.082 5 6.30e-9 5.58e-8 ✓ sig.
Growth hormone deficiency Hypogonadism 0.057 6 1.43e-8 1.19e-7 ✓ sig.
GPR161-related medulloblastoma predisposition Pituitary stalk interruption syndrome 0.031 1 2.01e-3 2.89e-3 ✓ sig.
Cohen syndrome Pituitary stalk interruption syndrome 0.031 1 2.01e-3 2.89e-3 ✓ sig.
hypogonadotropic hypogonadism 4 with or without anosmia Sheehan syndrome 0.029 1 2.21e-3 3.10e-3 ✓ sig.
hypogonadotropic hypogonadism 4 with or without anosmia Pituitary short stature 0.029 1 2.21e-3 3.10e-3 ✓ sig.
Growth hormone deficiency hypogonadotropic hypogonadism 4 with or without anosmia 0.029 1 2.21e-3 3.10e-3 ✓ sig.
hypogonadotropic hypogonadism 4 with or without anosmia Kallmann syndrome 0.026 1 2.47e-3 3.36e-3 ✓ sig.
amyotrophic lateral sclerosis type 15 Hypogonadism 0.013 1 4.94e-3 6.05e-3 ✓ sig.
Brody myopathy Hypogonadism 0.013 1 9.85e-3 1.12e-2 ✓ sig.