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Cluster 251

7 diseases · 8 shared-gene connections

7 Diseases

68 Unique genes

0.072 Avg. similarity score

Dysthymic disorder Most-connected disease (4 links)

Significant edges only (q < 0.05) Spacing Colour by

Disease Searched: Behavior disorders 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.

Behavior disorders Dysthymic disorder Anhedonia Panic disorder Asperger syndrome Early-onset obesity-hyperphagia-severe developmental delay syndrome

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

Disease ⇵	Connections in cluster ⇵	Significant partners ⇵	Curated genes ⇵
Dysthymic disorder	4	4	7
Anhedonia	3	3	26
Behavior disorders	3	3	1
Panic disorder	3	3	34
Asperger syndrome	1	1	9
Early-onset obesity-hyperphagia-severe developmental delay syndrome	1	1	1
Pemphigus foliaceus	1	1	1

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

Gene ⇵	Member diseases ⇵	Linked diseases
SLC6A4	4 / 7	Anhedonia, Asperger syndrome, Behavior disorders, Dysthymic disorder
CRH	3 / 7	Anhedonia, Dysthymic disorder, Panic disorder
COMT	2 / 7	Anhedonia, Panic disorder
DISC1	2 / 7	Anhedonia, Asperger syndrome
HTR1A	2 / 7	Anhedonia, Panic disorder
MAOA	2 / 7	Dysthymic disorder, Panic disorder
NTRK2	2 / 7	Dysthymic disorder, Early-onset obesity-hyperphagia-severe developmental delay syndrome
RAN	2 / 7	Panic disorder, Pemphigus foliaceus

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 ⇵
cAMP signaling pathway ATP1A3, CACNA1C, CRH, CRHR1, CRHR2, DRD2, HTR1A, KCNK2, MAPK1, VIP, ADORA2A, PDE4B	KEGG	12 / 226	9.4×	4.24e-9	3.90e-7 ✓ sig.
Hormone signaling CRH, CRHR1, CRHR2, DRD2, MC4R, OPRK1, VIP, ADRA2A, CCKBR, INS, SMAD1	KEGG	11 / 219	8.9×	3.55e-8	2.54e-6 ✓ sig.
Neuroactive ligand-receptor interaction CRH, CRHR1, CRHR2, DRD2, HTR1A, MC4R, OPRK1, VIP, ADORA2A, ADRA2A, CCKBR, GRM7	KEGG	12 / 370	5.7×	9.40e-7	4.45e-5 ✓ sig.
G alpha (s) signalling events CRH, CRHR1, CRHR2, MC4R, ARRB1, VIP, ADORA2A	Reactome	7 / 140	8.8×	1.35e-5	4.19e-4 ✓ sig.
Enzymatic degradation of Dopamine by monoamine oxidase COMT, MAOA	Reactome	2 / 2	177×	3.16e-5	8.51e-4 ✓ sig.
Serotonergic synapse CACNA1C, HTR1A, MAPK1, SLC6A4, MAOA, TPH2	KEGG	6 / 115	9.2×	4.56e-5	1.15e-3 ✓ sig.
ADORA2B mediated anti-inflammatory cytokines production CRH, CRHR1, CRHR2, MC4R, VIP, ADORA2A	Reactome	6 / 128	8.3×	8.31e-5	1.88e-3 ✓ sig.
Alcoholism CRH, DRD2, MAPK1, SLC6A3, MAOA, NTRK2, ADORA2A	KEGG	7 / 188	6.6×	8.92e-5	1.99e-3 ✓ sig.
Enzymatic degradation of dopamine by COMT COMT, MAOA	Reactome	2 / 3	118×	9.44e-5	2.08e-3 ✓ sig.
Dopaminergic synapse CACNA1C, COMT, DRD2, SLC6A3, ARRB1, MAOA	KEGG	6 / 132	8.0×	9.85e-5	2.16e-3 ✓ sig.
Class B/2 (Secretin family receptors) CRH, CRHR1, CRHR2	Reactome	3 / 18	29.4×	1.33e-4	2.75e-3 ✓ sig.
Cushing syndrome CACNA1C, CRH, CRHR1, CRHR2, KCNK2, MAPK1	KEGG	6 / 155	6.8×	2.37e-4	4.36e-3 ✓ sig.
Glutamatergic synapse CACNA1C, MAPK1, SLC17A7, SLC1A3, GRM7	KEGG	5 / 116	7.6×	4.95e-4	7.82e-3 ✓ sig.
Synaptic vesicle cycle SLC17A7, SLC1A3, SLC6A3, SLC6A4	KEGG	4 / 79	8.9×	1.03e-3	1.37e-2 ✓ sig.
Gastrin-CREB signalling pathway via PKC and MAPK MAPK1, CCKBR	Reactome	2 / 9	39.2×	1.11e-3	1.45e-2 ✓ 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 ⇵
response to cocaine CRH, DRD2, OPRK1, PITX3, SLC6A3	GO:0042220	5 / 35	39.3×	1.64e-7	1.83e-5 ✓ sig.
synaptic transmission, dopaminergic COMT, CRH, DRD2, ADORA2A	GO:0001963	4 / 15	73.3×	2.12e-7	2.28e-5 ✓ sig.
signal transduction ANK3, CCR6, CCR7, CRH, CRHR1, CRHR2, DRD2, GJA1, HTR1A, MAPK1, MC4R, OPRK1	GO:0007165	23 / 2,125	3.0×	8.31e-7	7.11e-5 ✓ sig.
fear response COMT, CRHR1, ADRA2A	GO:0042596	3 / 8	103×	2.55e-6	1.76e-4 ✓ sig.
G protein-coupled receptor signaling pathway CCR6, CCR7, CRHR1, CRHR2, DRD2, HTR1A, KCNK2, MC4R, OPRK1, VIP, ADORA2A, ADRA2A	GO:0007186	15 / 1,031	4.0×	3.40e-6	2.22e-4 ✓ sig.
phospholipase C-activating G protein-coupled receptor signaling pathway DRD2, OPRK1, RASGRP4, GAP43, ADORA2A, CCKBR	GO:0007200	6 / 120	13.7×	4.89e-6	2.97e-4 ✓ sig.
glutamate secretion GJA1, KCNK2, NTRK2	GO:0014047	3 / 11	74.9×	7.45e-6	4.17e-4 ✓ sig.
dopamine catabolic process COMT, SLC6A3, MAOA	GO:0042420	3 / 11	74.9×	7.45e-6	4.17e-4 ✓ sig.
cellular response to cocaine COMT, CRH, SLC1A3	GO:0071314	3 / 11	74.9×	7.45e-6	4.17e-4 ✓ sig.
cell communication by electrical coupling involved in cardiac conduction ATP1A3, CACNA1C, GJA1	GO:0086064	3 / 12	68.7×	9.90e-6	5.22e-4 ✓ sig.
regulation of serotonin secretion CRH, HTR1A	GO:0014062	2 / 2	275×	1.30e-5	6.47e-4 ✓ sig.
response to nicotine DRD2, MAPK1, OPRK1, SLC6A3	GO:0035094	4 / 40	27.5×	1.33e-5	6.56e-4 ✓ sig.
positive regulation of gene expression ANK3, CRH, GJA1, SLC6A4, NTRK2, CALCOCO1, CLU, INS, PKP1, SMAD1	GO:0010628	10 / 504	5.5×	1.33e-5	6.58e-4 ✓ sig.
prepulse inhibition DRD2, SLC6A3, ADORA2A	GO:0060134	3 / 14	58.9×	1.63e-5	7.71e-4 ✓ sig.
chemical synaptic transmission CRH, HTR1A, MAPK1, OPRK1, SLC17A7, SLC1A3, GRM7	GO:0007268	7 / 236	8.2×	2.36e-5	1.02e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵	Disease B ⇵	Similarity score ⇵	Shared genes ⇵	P-value ⇵	FDR q-value ⇵
Anhedonia	Panic disorder	0.052	3	2.47e-5	1.16e-4 ✓ sig.
Anhedonia	Dysthymic disorder	0.063	2	5.73e-5	2.33e-4 ✓ sig.
Dysthymic disorder	Panic disorder	0.050	2	9.87e-5	3.50e-4 ✓ sig.
Behavior disorders	Dysthymic disorder	0.125	1	4.55e-4	9.72e-4 ✓ sig.
Dysthymic disorder	Early-onset obesity-hyperphagia-severe developmental delay syndrome	0.125	1	4.55e-4	9.72e-4 ✓ sig.
Asperger syndrome	Behavior disorders	0.100	1	5.84e-4	1.16e-3 ✓ sig.
Anhedonia	Behavior disorders	0.037	1	1.69e-3	2.53e-3 ✓ sig.
Panic disorder	Pemphigus foliaceus	0.029	1	2.21e-3	3.11e-3 ✓ sig.

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