BCL11B

BCL11 transcription factor B, the group of Zinc fingers C2H2-type|BAF complex

Basic information

Region (hg38): 14:99169286-99272197

Previous symbols: [ "ZNF856B" ]

Links

ENSG00000127152 ∙ NCBI:64919 ∙ OMIM:606558 ∙ HGNC:13222 ∙ Uniprot:Q9C0K0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 49 (Limited), mode of inheritance: AD
• intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities (Moderate), mode of inheritance: AD
• intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities (Definitive), mode of inheritance: AD
• immunodeficiency 49 (Strong), mode of inheritance: AD
• immunodeficiency 49 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 49; Intellectual developmental disorder with speech delay, dysmorphic facies, and T-cell abnormalities	AD	Allergy/Immunology/Infectious	Among other features, individuals have been described as susceptible to severe or frequent infections, and awareness may allow preventative measures and early and aggressive treatment of infections; In Immunodeficiency 49, HSCT has been described	Allergy/Immunology/Infectious; Craniofacial; Dental; Dermatologic; Neurologic; Musculoskeletal	27959755; 29985992

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BCL11B gene.

• not provided (449 variants)
• Inborn genetic diseases (32 variants)
• Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities (25 variants)
• BCL11B-related condition (10 variants)
• Immunodeficiency 49 (9 variants)
• BCL11B-related BAFopathy (7 variants)
• not specified (5 variants)
• See cases (3 variants)
• Immunodeficiency 49;Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities (2 variants)
• Autism (1 variants)
• Microcephaly (1 variants)
• Autism spectrum disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BCL11B gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	175	9	186
missense		4	204	8	10	226
nonsense	5	2	1			8
start loss						0
frameshift	20	10	5			35
inframe indel			15	6	2	23
splice donor/acceptor (+/-2bp)						0
splice region				3	2	5
non coding				14	3	17
Total	25	16	227	203	24

Variants in BCL11B

This is a list of pathogenic ClinVar variants found in the BCL11B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-99174149-G-A		BCL11B-related disorder	Likely benign (Apr 25, 2019)
14-99174156-T-G			Uncertain significance (Feb 01, 2023)
14-99174164-GC-G		Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities	Pathogenic (Aug 28, 2018)
14-99174172-G-C			Uncertain significance (Jul 28, 2023)
14-99174174-T-C			Uncertain significance (Jan 01, 2023)
14-99174183-C-T			Uncertain significance (Jan 01, 2024)
14-99174183-CGTTA-C			Uncertain significance (May 16, 2023)
14-99174190-C-A			Likely benign (Dec 02, 2021)
14-99174195-A-C			Uncertain significance (Sep 26, 2022)
14-99174196-G-C			Benign (Nov 28, 2022)
14-99174199-C-G			Uncertain significance (Dec 11, 2023)
14-99174201-C-T			Uncertain significance (Mar 23, 2023)
14-99174204-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 22, 2023)
14-99174211-C-T			Likely benign (Jul 16, 2023)
14-99174214-T-C			Benign (Sep 20, 2023)
14-99174218-ATG-A			Likely pathogenic (Aug 13, 2019)
14-99174229-C-T			Likely benign (Mar 29, 2023)
14-99174230-AG-A		Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities	Pathogenic (-)
14-99174232-G-C			Likely benign (Jan 04, 2022)
14-99174240-AG-A		BCL11B-related disorder	Likely pathogenic (Apr 17, 2023)
14-99174265-G-A			Likely benign (May 31, 2021)
14-99174271-G-A			Likely benign (Jan 19, 2024)
14-99174277-C-T			Likely benign (Jun 27, 2022)
14-99174281-T-A			Uncertain significance (Nov 15, 2022)
14-99174294-G-A			Uncertain significance (Dec 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BCL11B	protein_coding	protein_coding	ENST00000357195	4	102238

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.989	0.0112	124392	0	2	124394	0.00000804

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.71	237	547	0.433	0.0000408	5691
Missense in Polyphen		21	95.167	0.22066		966
Synonymous	-1.35	314	285	1.10	0.0000265	1827
Loss of Function	3.99	2	22.4	0.0895	0.00000110	259

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000298	0.0000298
Ashkenazi Jewish	0.000102	0.000100
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key regulator of both differentiation and survival of T- lymphocytes during thymocyte development in mammals. Essential in controlling the responsiveness of hematopoietic stem cells to chemotactic signals by modulating the expression of the receptors CCR7 and CCR9, which direct the movement of progenitor cells from the bone marrow to the thymus (PubMed:27959755). Is a regulator of IL2 promoter and enhances IL2 expression in activated CD4(+) T- lymphocytes (PubMed:16809611). Tumor-suppressor that represses transcription through direct, TFCOUP2-independent binding to a GC- rich response element (By similarity). May also function in the P53-signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q99PV8, ECO:0000269|PubMed:16809611, ECO:0000269|PubMed:27959755}.
• Disease: DISEASE: Immunodeficiency 49 (IMD49) [MIM:617237]: A form of severe combined immunodeficiency characterized by severe T-cell lymphopenia, no detectable T-cell receptor excision circles, no naive helper CD4+ T-cells, and impaired T-cell proliferative response. In addition to primary immunodeficiency, affected individuals manifest multiple abnormal systemic features, including severe delayed psychomotor development, intellectual disability, spastic quadriplegia, and craniofacial abnormalities. {ECO:0000269|PubMed:27959755}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Transcriptional misregulation in cancer - Homo sapiens (human);Development and heterogeneity of the ILC family (Consensus)

Recessive Scores

• pRec: 0.162

Haploinsufficiency Scores

• pHI: 0.701
• hipred: Y
• hipred_score: 0.853
• ghis: 0.570

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Bcl11b
• Phenotype: craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; growth/size/body region phenotype; vision/eye phenotype; skeleton phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm

Gene ontology

• Biological process: keratinocyte development;epithelial cell morphogenesis;regulation of transcription, DNA-templated;negative regulation of cell population proliferation;regulation of keratinocyte proliferation;regulation of lipid metabolic process;striatal medium spiny neuron differentiation;commitment of neuronal cell to specific neuron type in forebrain;post-embryonic camera-type eye development;T cell differentiation in thymus;T cell receptor V(D)J recombination;hematopoietic stem cell migration;odontogenesis of dentin-containing tooth;negative regulation of apoptotic process;positive T cell selection;regulation of neuron differentiation;positive regulation of transcription by RNA polymerase II;alpha-beta T cell differentiation;thymus development;olfactory bulb axon guidance;lymphoid lineage cell migration into thymus
• Cellular component: nucleus;neuron projection
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;sequence-specific DNA binding;metal ion binding