Immunodeficiency 49

Summary

Immunodeficiency 49 (MONDO:0014981) is a disease caused by BCL11B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: BCL11B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 49
Mondo ID	MONDO:0014981
OMIM	617237
DOID	DOID:0111979
UMLS	C4310656
MedGen	934623
GARD	0025043
Is cancer (heuristic)	no

Also known as: BCL11B primary immunodeficiency disease · IMD49 · immunodeficiency 49; IMD49 · immunodeficiency type 49 · primary immunodeficiency disease caused by mutation in BCL11B

Data availability: 20 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › immunodeficiency 49

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 37, immunodeficiency 39, BENTA disease, primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection, 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

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

20 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 3 pathogenic, 3 conflicting classifications of pathogenicity, 1 benign/likely benign, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1275761	NM_138576.4(BCL11B):c.1887_1893del (p.Gly630fs)	BCL11B	Pathogenic	criteria provided, multiple submitters, no conflicts
1292051	NM_138576.4(BCL11B):c.2448_2461dup (p.Glu821fs)	BCL11B	Pathogenic	criteria provided, multiple submitters, no conflicts
254673	NM_138576.4(BCL11B):c.1323T>G (p.Asn441Lys)	BCL11B	Pathogenic	no assertion criteria provided
560174	NM_138576.4(BCL11B):c.2421C>G (p.Asn807Lys)	BCL11B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382096	NM_138576.4(BCL11B):c.1707del (p.Gly570fs)	BCL11B	Likely pathogenic	criteria provided, single submitter
1712805	NM_138576.4(BCL11B):c.473C>T (p.Ala158Val)	BCL11B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2089004	NM_138576.4(BCL11B):c.1996C>T (p.Pro666Ser)	BCL11B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2497802	NM_138576.4(BCL11B):c.2108C>A (p.Pro703Gln)	BCL11B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029132	NM_138576.4(BCL11B):c.1003A>G (p.Met335Val)	BCL11B	Uncertain significance	criteria provided, single submitter
1029133	NM_138576.4(BCL11B):c.296C>T (p.Pro99Leu)	BCL11B	Uncertain significance	criteria provided, single submitter
1033088	NM_138576.4(BCL11B):c.906C>A (p.His302Gln)	BCL11B	Uncertain significance	criteria provided, single submitter
1334063	NM_138576.4(BCL11B):c.908C>A (p.Pro303Gln)	BCL11B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1675189	NM_138576.4(BCL11B):c.740G>A (p.Arg247His)	BCL11B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2500080	NM_138576.4(BCL11B):c.992G>T (p.Ser331Ile)	BCL11B	Uncertain significance	criteria provided, single submitter
2671733	NM_138576.4(BCL11B):c.307C>A (p.Arg103Ser)	BCL11B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3067947	NM_138576.4(BCL11B):c.1644C>A (p.Asn548Lys)	BCL11B	Uncertain significance	criteria provided, single submitter
3576918	NM_138576.4(BCL11B):c.1219C>G (p.Pro407Ala)	BCL11B	Uncertain significance	criteria provided, single submitter
4278144	NM_138576.4(BCL11B):c.2467C>A (p.Pro823Thr)	BCL11B	Uncertain significance	criteria provided, single submitter
4293851	NM_138576.4(BCL11B):c.979C>T (p.Pro327Ser)	BCL11B	Uncertain significance	criteria provided, single submitter
1568539	NM_138576.4(BCL11B):c.1521C>T (p.Gly507=)	BCL11B	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
BCL11B	Strong	Autosomal dominant	immunodeficiency 49	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BCL11B	Orphanet:662829	Intellectual disability-speech delay-dysmorphic features-T cell abnormalities syndrome

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
BCL11B	HGNC:13222	ENSG00000127152	Q9C0K0	B-cell lymphoma/leukemia 11B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BCL11B	B-cell lymphoma/leukemia 11B	Key regulator of both differentiation and survival of T-lymphocytes during thymocyte development in mammals.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BCL11B	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Dev/Hematopoietic_TF

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
cortical plate	1
thymus	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BCL11B	211	broad	marker	thymus, upper leg skin, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BCL11B	2,523

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BCL11B	Q9C0K0	51.76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Formation of the embryonic stem cell BAF (esBAF) complex	1	601.0×	0.002	BCL11B
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	456.8×	0.002	BCL11B

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
olfactory bulb axon guidance	1	16852.0×	7e-04	BCL11B
positive T cell selection	1	8426.0×	7e-04	BCL11B
lymphoid lineage cell migration into thymus	1	8426.0×	7e-04	BCL11B
striatal medium spiny neuron differentiation	1	4213.0×	7e-04	BCL11B
post-embryonic camera-type eye development	1	4213.0×	7e-04	BCL11B
T cell receptor V(D)J recombination	1	4213.0×	7e-04	BCL11B
hematopoietic stem cell migration	1	4213.0×	7e-04	BCL11B
commitment of neuronal cell to specific neuron type in forebrain	1	2808.7×	1e-03	BCL11B
alpha-beta T cell differentiation	1	1872.4×	0.001	BCL11B
negative regulation of thymocyte apoptotic process	1	1685.2×	0.001	BCL11B
keratinocyte development	1	1532.0×	0.001	BCL11B
regulation of keratinocyte proliferation	1	1532.0×	0.001	BCL11B
thymocyte apoptotic process	1	1404.3×	0.001	BCL11B
epithelial cell morphogenesis	1	936.2×	0.002	BCL11B
regulation of neuron differentiation	1	732.7×	0.002	BCL11B
regulation of lipid metabolic process	1	432.1×	0.003	BCL11B
T cell differentiation in thymus	1	411.0×	0.003	BCL11B
thymus development	1	337.0×	0.004	BCL11B
odontogenesis of dentin-containing tooth	1	300.9×	0.004	BCL11B
transcription by RNA polymerase II	1	70.5×	0.016	BCL11B
negative regulation of cell population proliferation	1	42.1×	0.025	BCL11B
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	BCL11B

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
BCL11B	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	BCL11B

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)
BCL11B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.