Immunodeficiency 37

Summary

Immunodeficiency 37 (MONDO:0014491) is a disease caused by BCL10 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: BCL10 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 112

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 37
Mondo ID	MONDO:0014491
OMIM	616098
DOID	DOID:0111939
UMLS	C4015195
MedGen	863632
GARD	0024994
Is cancer (heuristic)	no

Also known as: BCL10 primary immunodeficiency disease · combined immunodeficiency due to BCL10 deficiency · IMD37 · immunodeficiency 37 · immunodeficiency type 37 · primary immunodeficiency disease caused by mutation in BCL10

Data availability: 112 ClinVar variants · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › immunodeficiency 37

Related subtypes (40): B cell deficiency, complement deficiency, phagocyte bactericidal dysfunction, trichohepatoenteric syndrome, hepatic veno-occlusive disease-immunodeficiency syndrome, immunodeficiency with defective T-cell response to interleukin 1, Say-Barber-Miller syndrome, familial isolated congenital asplenia, X-linked immunoneurologic disorder, ectodermal dysplasia and immune deficiency, immunodeficiency 33, immunodeficiency 47, combined immunodeficiency due to moesin deficiency, immunodeficiency, X-linked, with deficiency of 115,000 Dalton surface glycoprotein, properdin deficiency, X-linked, combined immunodeficiency with faciooculoskeletal anomalies, recurrent infections associated with rare immunoglobulin isotypes deficiency, immunodeficiency 28, autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity, immunodeficiency 39, BENTA disease, primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection, immunodeficiency 49, chronic mucocutaneous candidiasis, hereditary hemophagocytic lymphohistiocytosis, immunoglobulin heavy chain deficiency, immuno-osseous dysplasia, lymphoproliferative syndrome, IL10-related early-onset inflammatory bowel disease, T-cell immunodeficiency with epidermodysplasia verruciformis, Aicardi-Goutieres syndrome, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, inflammatory bowel disease-recurrent sinopulmonary infections syndrome, A20 haploinsufficiency, NK cell deficiency, T cell and NK cell immunodeficiency, dendritic cell deficiency, immunodysregulation with variable immunodeficiency and autoimmunity, immune dysregulation with immunodeficiency due to AIOLOS haploinsufficiency, STAT5 haploinsufficiency

Subtypes (1): combined immunodeficiency with low Ig due to BCL10 deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

112 retrieved; paginated sample, class counts are floors:

51 likely benign, 47 uncertain significance, 6 pathogenic, 5 benign, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
160347	NM_003921.5(BCL10):c.57+1G>A	BCL10	Pathogenic	no assertion criteria provided
1968159	NM_003921.5(BCL10):c.14dup (p.Pro6fs)	BCL10	Pathogenic	criteria provided, single submitter
2086361	NM_003921.5(BCL10):c.217C>T (p.Gln73Ter)	BCL10	Pathogenic	criteria provided, single submitter
3651130	NM_003921.5(BCL10):c.207dup (p.Asp70fs)	BCL10	Pathogenic	criteria provided, single submitter
4691162	NM_003921.5(BCL10):c.262C>T (p.Arg88Ter)	BCL10	Pathogenic	criteria provided, single submitter
6266	NM_003921.5(BCL10):c.172C>T (p.Arg58Ter)	BCL10	Pathogenic	criteria provided, single submitter
1003339	NM_003921.5(BCL10):c.260G>A (p.Arg87Gln)	BCL10	Uncertain significance	criteria provided, single submitter
1009636	NM_003921.5(BCL10):c.58G>A (p.Ala20Thr)	BCL10	Uncertain significance	criteria provided, single submitter
1019881	NM_003921.5(BCL10):c.682C>T (p.Arg228Cys)	BCL10	Uncertain significance	criteria provided, single submitter
1021998	NM_003921.5(BCL10):c.286A>G (p.Ile96Val)	BCL10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1042576	NM_003921.5(BCL10):c.360_362dup (p.Ser121dup)	BCL10	Uncertain significance	criteria provided, single submitter
1055135	NM_003921.5(BCL10):c.419del (p.Glu140fs)	BCL10	Uncertain significance	criteria provided, single submitter
1056866	NM_003921.5(BCL10):c.649A>G (p.Asn217Asp)	BCL10	Uncertain significance	criteria provided, single submitter
1063260	NM_003921.5(BCL10):c.76G>A (p.Val26Ile)	BCL10	Uncertain significance	criteria provided, single submitter
1347618	NM_003921.5(BCL10):c.325A>G (p.Ile109Val)	BCL10	Uncertain significance	criteria provided, single submitter
1373053	NM_003921.5(BCL10):c.568A>G (p.Thr190Ala)	BCL10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1399484	NM_003921.5(BCL10):c.395A>G (p.Asn132Ser)	BCL10	Uncertain significance	criteria provided, single submitter
1449095	NM_003921.5(BCL10):c.685A>T (p.Thr229Ser)	BCL10	Uncertain significance	criteria provided, single submitter
1467639	NM_003921.5(BCL10):c.28G>A (p.Glu10Lys)	BCL10	Uncertain significance	criteria provided, single submitter
1471908	NM_003921.5(BCL10):c.695G>A (p.Arg232Gln)	BCL10	Uncertain significance	criteria provided, single submitter
1476290	NM_003921.5(BCL10):c.433G>C (p.Glu145Gln)	BCL10	Uncertain significance	criteria provided, single submitter
1507303	NM_003921.5(BCL10):c.578C>T (p.Pro193Leu)	BCL10	Uncertain significance	criteria provided, single submitter
1714882	NM_003921.5(BCL10):c.356G>A (p.Cys119Tyr)	BCL10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1715183	NM_003921.5(BCL10):c.529C>A (p.Leu177Ile)	BCL10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1996333	NM_003921.5(BCL10):c.1A>T (p.Met1Leu)	BCL10	Uncertain significance	criteria provided, single submitter
2063733	NM_003921.5(BCL10):c.485C>T (p.Thr162Met)	BCL10	Uncertain significance	criteria provided, single submitter
2068200	NM_003921.5(BCL10):c.425A>G (p.Asn142Ser)	BCL10	Uncertain significance	criteria provided, single submitter
2126410	NM_003921.5(BCL10):c.20C>G (p.Ser7Cys)	BCL10	Uncertain significance	criteria provided, single submitter
2156003	NM_003921.5(BCL10):c.424A>C (p.Asn142His)	BCL10	Uncertain significance	criteria provided, single submitter
2185746	NM_003921.5(BCL10):c.505A>C (p.Asn169His)	BCL10	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
BCL10	Strong	Autosomal recessive	immunodeficiency 37	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BCL10	Orphanet:52417	MALT lymphoma

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BCL10	HGNC:989	ENSG00000142867	O95999	B-cell lymphoma/leukemia 10	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BCL10	B-cell lymphoma/leukemia 10	Plays a key role in both adaptive and innate immune signaling by bridging CARD domain-containing proteins to immune activation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BCL10	Other/Unknown	no		CARD, DEATH-like_dom_sf, BCL10/E10

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
esophagus squamous epithelium	1
mucosa of sigmoid colon	1
squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BCL10	280	ubiquitous	marker	esophagus squamous epithelium, mucosa of sigmoid colon, squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BCL10	1,873

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BCL10	O95999	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Downstream signaling events of B Cell Receptor (BCR)	1	815.7×	0.010	BCL10
Protein ubiquitination	1	815.7×	0.010	BCL10
TCR signaling	1	496.5×	0.010	BCL10
Signaling by the B Cell Receptor (BCR)	1	346.1×	0.010	BCL10
Fc epsilon receptor (FCERI) signaling	1	271.9×	0.010	BCL10
C-type lectin receptors (CLRs)	1	237.9×	0.010	BCL10
Activation of NF-kappaB in B cells	1	196.9×	0.010	BCL10
E3 ubiquitin ligases ubiquitinate target proteins	1	193.6×	0.010	BCL10
FCERI mediated NF-kB activation	1	156.4×	0.011	BCL10
CLEC7A (Dectin-1) signaling	1	142.8×	0.011	BCL10
Downstream TCR signaling	1	128.3×	0.011	BCL10
Adaptive Immune System	1	29.8×	0.045	BCL10
Innate Immune System	1	25.5×	0.048	BCL10
Post-translational protein modification	1	19.2×	0.060	BCL10
Immune System	1	13.0×	0.081	BCL10
Metabolism of proteins	1	12.4×	0.081	BCL10

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of lymphotoxin A production	1	5617.3×	0.003	BCL10
negative regulation of mature B cell apoptotic process	1	4213.0×	0.003	BCL10
positive regulation of mast cell cytokine production	1	3370.4×	0.003	BCL10
quinolinate biosynthetic process	1	1532.0×	0.004	BCL10
B cell apoptotic process	1	1404.3×	0.004	BCL10
programmed cell death	1	1296.3×	0.004	BCL10
T cell apoptotic process	1	1296.3×	0.004	BCL10
antifungal innate immune response	1	936.2×	0.004	BCL10
non-canonical NF-kappaB signal transduction	1	842.6×	0.004	BCL10
positive regulation of phosphorylation	1	842.6×	0.004	BCL10
positive regulation of T cell receptor signaling pathway	1	766.0×	0.004	BCL10
immunoglobulin mediated immune response	1	702.2×	0.004	BCL10
toll-like receptor signaling pathway	1	601.9×	0.004	BCL10
lipopolysaccharide-mediated signaling pathway	1	526.6×	0.004	BCL10
response to food	1	495.6×	0.004	BCL10
positive regulation of extrinsic apoptotic signaling pathway	1	455.5×	0.004	BCL10
positive regulation of T cell activation	1	443.5×	0.004	BCL10
cellular defense response	1	318.0×	0.006	BCL10
positive regulation of interleukin-8 production	1	244.2×	0.007	BCL10
apoptotic signaling pathway	1	224.7×	0.007	BCL10
cellular response to mechanical stimulus	1	216.1×	0.007	BCL10
positive regulation of protein ubiquitination	1	213.3×	0.007	BCL10
obsolete positive regulation of NF-kappaB transcription factor activity	1	205.5×	0.007	BCL10
neural tube closure	1	187.2×	0.007	BCL10
positive regulation of interleukin-6 production	1	166.8×	0.008	BCL10
T cell receptor signaling pathway	1	151.8×	0.008	BCL10
protein homooligomerization	1	122.1×	0.010	BCL10
cellular response to lipopolysaccharide	1	98.0×	0.012	BCL10
adaptive immune response	1	84.3×	0.014	BCL10
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.015	BCL10

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BCL10	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	BCL10

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
BCL10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.