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Cluster 263

8 diseases · 20 shared-gene connections

8 Diseases

7 Unique genes

0.302 Avg. similarity score

Combined cellular and humoral immune defects with granulomas Most-connected disease (7 links)

Significant edges only (q < 0.05) Spacing Colour by

Disease Searched: Recombinase activating gene 1 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.

Recombinase activating gene 1 deficiency Combined cellular and humoral immune defects with granulomas Combined immunodeficiency with granulomatosis T-B- severe combined immunodeficiency Recombinase activating gene 2 deficiency Severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-positive

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

Disease ⇵	Connections in cluster ⇵	Significant partners ⇵	Curated genes ⇵
Combined cellular and humoral immune defects with granulomas	7	7	2
Combined immunodeficiency with granulomatosis	6	6	3
T-B- severe combined immunodeficiency	6	6	5
Recombinase activating gene 2 deficiency	5	5	1
Severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-positive	5	5	1
Alpha/beta t-cell lymphopenia, with gamma/delta t-cell expansion, severe cytomegalovirus infection and autoimmunity	4	4	1
Recombinase activating gene 1 deficiency	4	4	1
Salla disease	3	3	2

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

Gene ⇵	Member diseases ⇵	Linked diseases
RAG2	6 / 8	Combined cellular and humoral immune defects with granulomas, Combined immunodeficiency with granulomatosis, Recombinase activating gene 2 deficiency, Salla disease and 2 more
RAG1	5 / 8	Alpha/beta t-cell lymphopenia, with gamma/delta t-cell expansion, severe cytomegalovirus infection and autoimmunity, Combined cellular and humoral immune defects with granulomas, Combined immunodeficiency with granulomatosis, Recombinase activating gene 1 deficiency and 1 more

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 ⇵
Primary immunodeficiency RAG1, RAG2, DCLRE1C	KEGG	3 / 38	135×	1.01e-6	4.21e-5 ✓ sig.
Non-homologous end-joining DCLRE1C, LIG4	KEGG	2 / 13	264×	2.26e-5	5.77e-4 ✓ sig.
Defective SLC17A5 causes Salla disease (SD) and ISSD SLC17A5	Reactome	1 / 1	1,716×	5.83e-4	7.52e-3 ✓ sig.
Nonhomologous End-Joining (NHEJ) DCLRE1C, LIG4	Reactome	2 / 69	49.7×	6.71e-4	8.35e-3 ✓ sig.
MAPK6/MAPK4 signaling RAG1, RAG2	Reactome	2 / 89	38.6×	1.11e-3	1.23e-2 ✓ sig.
FoxO signaling pathway RAG1, RAG2	KEGG	2 / 133	25.8×	2.46e-3	2.22e-2 ✓ sig.
2-LTR circle formation LIG4	Reactome	1 / 7	245×	4.07e-3	3.17e-2 ✓ sig.
Organic anion transporters SLC17A5	Reactome	1 / 10	172×	5.82e-3	4.03e-2 ✓ sig.
PCP/CE pathway RAC2	Reactome	1 / 18	95.3×	1.04e-2	5.84e-2
RHO GTPases Activate NADPH Oxidases RAC2	Reactome	1 / 24	71.5×	1.39e-2	6.94e-2
Sialic acid metabolism SLC17A5	Reactome	1 / 33	52.0×	1.91e-2	8.33e-2
ROS and RNS production in phagocytes RAC2	Reactome	1 / 34	50.5×	1.97e-2	8.49e-2
GPVI-mediated activation cascade RAC2	Reactome	1 / 34	50.5×	1.97e-2	8.49e-2
DNA Damage Recognition in GG-NER INO80	Reactome	1 / 38	45.2×	2.19e-2	9.03e-2
VEGF signaling pathway RAC2	KEGG	1 / 60	28.6×	3.45e-2	1.17e-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 ⇵
V(D)J recombination RAG1, RAG2, DCLRE1C, LIG4	GO:0033151	4 / 11	971×	2.27e-12	1.00e-9 ✓ sig.
DNA recombination RAG1, RAG2, INO80, DCLRE1C, LIG4	GO:0006310	5 / 110	121×	1.34e-10	3.97e-8 ✓ sig.
T cell differentiation in thymus RAG1, RAG2, LIG4	GO:0033077	3 / 41	195×	3.41e-7	3.54e-5 ✓ sig.
chromosome organization INO80, DCLRE1C, LIG4	GO:0051276	3 / 51	157×	6.65e-7	6.16e-5 ✓ sig.
DN2 thymocyte differentiation RAG2, LIG4	GO:1904155	2 / 4	1,335×	7.21e-7	6.58e-5 ✓ sig.
pre-B cell allelic exclusion RAG1, RAG2	GO:0002331	2 / 4	1,335×	7.21e-7	6.58e-5 ✓ sig.
B cell differentiation RAG1, RAG2, DCLRE1C	GO:0030183	3 / 80	100×	2.61e-6	1.88e-4 ✓ sig.
double-strand break repair INO80, DCLRE1C, LIG4	GO:0006302	3 / 87	92.1×	3.37e-6	2.30e-4 ✓ sig.
cellular response to ionizing radiation INO80, LIG4	GO:0071479	2 / 41	130×	9.79e-5	3.04e-3 ✓ sig.
DNA metabolic process INO80, DCLRE1C	GO:0006259	2 / 43	124×	1.08e-4	3.27e-3 ✓ sig.
double-strand break repair via nonhomologous end joining DCLRE1C, LIG4	GO:0006303	2 / 45	119×	1.18e-4	3.49e-3 ✓ sig.
response to ionizing radiation DCLRE1C, LIG4	GO:0010212	2 / 47	114×	1.29e-4	3.71e-3 ✓ sig.
telomere maintenance INO80, DCLRE1C	GO:0000723	2 / 66	80.9×	2.55e-4	6.04e-3 ✓ sig.
DNA repair INO80, DCLRE1C, LIG4	GO:0006281	3 / 420	19.1×	3.69e-4	7.78e-3 ✓ sig.
establishment of integrated proviral latency LIG4	GO:0075713	1 / 1	2,670×	3.75e-4	7.81e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵	Disease B ⇵	Similarity score ⇵	Shared genes ⇵	P-value ⇵	FDR q-value ⇵
Combined cellular and humoral immune defects with granulomas	Combined immunodeficiency with granulomatosis	0.500	2	2.50e-8	1.87e-7 ✓ sig.
Combined cellular and humoral immune defects with granulomas	T-B- severe combined immunodeficiency	0.333	2	8.34e-8	5.85e-7 ✓ sig.
Combined immunodeficiency with granulomatosis	T-B- severe combined immunodeficiency	0.286	2	2.50e-7	1.65e-6 ✓ sig.
Alpha/beta t-cell lymphopenia, with gamma/delta t-cell expansion, severe cytomegalovirus infection and autoimmunity	Recombinase activating gene 1 deficiency	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Recombinase activating gene 2 deficiency	Severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-positive	0.500	1	6.46e-5	1.98e-4 ✓ sig.
Alpha/beta t-cell lymphopenia, with gamma/delta t-cell expansion, severe cytomegalovirus infection and autoimmunity	Combined cellular and humoral immune defects with granulomas	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Combined cellular and humoral immune defects with granulomas	Severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-positive	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Combined cellular and humoral immune defects with granulomas	Recombinase activating gene 1 deficiency	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Combined cellular and humoral immune defects with granulomas	Recombinase activating gene 2 deficiency	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Salla disease	Severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-positive	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Recombinase activating gene 2 deficiency	Salla disease	0.333	1	1.29e-4	3.27e-4 ✓ sig.
Combined immunodeficiency with granulomatosis	Recombinase activating gene 2 deficiency	0.250	1	1.94e-4	4.41e-4 ✓ sig.
Combined immunodeficiency with granulomatosis	Severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-positive	0.250	1	1.94e-4	4.41e-4 ✓ sig.
Combined immunodeficiency with granulomatosis	Recombinase activating gene 1 deficiency	0.250	1	1.94e-4	4.41e-4 ✓ sig.
Alpha/beta t-cell lymphopenia, with gamma/delta t-cell expansion, severe cytomegalovirus infection and autoimmunity	Combined immunodeficiency with granulomatosis	0.250	1	1.94e-4	4.41e-4 ✓ sig.
Combined cellular and humoral immune defects with granulomas	Salla disease	0.250	1	2.58e-4	5.38e-4 ✓ sig.
Recombinase activating gene 1 deficiency	T-B- severe combined immunodeficiency	0.167	1	3.23e-4	6.41e-4 ✓ sig.
Recombinase activating gene 2 deficiency	T-B- severe combined immunodeficiency	0.167	1	3.23e-4	6.41e-4 ✓ sig.
Alpha/beta t-cell lymphopenia, with gamma/delta t-cell expansion, severe cytomegalovirus infection and autoimmunity	T-B- severe combined immunodeficiency	0.167	1	3.23e-4	6.41e-4 ✓ sig.
Severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-positive	T-B- severe combined immunodeficiency	0.167	1	3.23e-4	6.41e-4 ✓ sig.

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