BCL11A

Chr 2AD

BCL11 transcription factor A

Also known as: CTIP1, DILOS, EVI9, HBFQTL5, SMARCM1, ZNF856

This gene encodes a C2H2 type zinc-finger protein by its similarity to the mouse Bcl11a/Evi9 protein. The corresponding mouse gene is a common site of retroviral integration in myeloid leukemia, and may function as a leukemia disease gene, in part, through its interaction with BCL6. During hematopoietic cell differentiation, this gene is down-regulated. It is possibly involved in lymphoma pathogenesis since translocations associated with B-cell malignancies also deregulates its expression. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
LOFmechanismADLOEUF 0.321 OMIM phenotype
Clinical SummaryBCL11A
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Gene-Disease Validity (ClinGen)
Dias-Logan syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 57 VUS of 96 total submissions
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Clinical Trials
10 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?
0.32LOEUF
pLI 0.970
Z-score 3.98
OE 0.12 (0.060.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
3.84Z-score
OE missense 0.54 (0.490.59)
296 obs / 548.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.12 (0.060.32)
00.351.4
Missense OE?0.54 (0.490.59)
00.61.4
Synonymous OE?0.83
01.21.6
LoF obs/exp: 3 / 24.1Missense obs/exp: 296 / 548.8Syn Z: 2.10
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveBCL11A-related intellectual disabilityLOFAD

This gene — mechanism propensity

DN
0.3296th %ile
GOF
0.2099th %ile
LOF
0.85top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 93% of P/LP variants are LoF · LOEUF 0.32 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFThus, our work implicates BCL11A haploinsufficiency in neurodevelopmental disorders and defines additional targets regulated by this gene, with broad relevance for our understanding of ID and related syndromes.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

  1. 1.PMID 27453576

ClinVar Variant Classifications

96 submitted variants in ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic9
VUS57
Likely Benign7
Benign1
Conflicting1
5
Pathogenic
9
Likely Pathogenic
57
VUS
7
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
0
0
5
Likely Pathogenic
8
1
0
0
9
VUS
2
51
3
1
57
Likely Benign
0
4
0
3
7
Benign
0
0
0
1
1
Conflicting
1
Total15563580

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

3 pathogenic / likely-pathogenic (of 4) ClinVar copy-number / structural variants overlap BCL11A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

BCL11A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10
Beta-ThalassemiaThalassemiaGenetic Diseases, Inborn

Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Transfusion-Dependent β-Thalassemia (TDT)

ACTIVE NOT RECRUITING
NCT05356195Phase PHASE3Vertex Pharmaceuticals IncorporatedStarted 2022-05-03
CTX001
Sickle Cell Disease

A Gene Transfer Study Inducing Fetal Hemoglobin in Sickle Cell Disease (GRASP, BMT CTN 2001)

ACTIVE NOT RECRUITING
NCT05353647Phase PHASE2David WilliamsStarted 2022-07-12
Autologous CD34+ HSC cells transduced with the lentiviral vector containing a shRNA targeting BCL11a
Sickle Cell Disease

Long-term Follow-up (LTFU) of Patients Treated With Genome-edited Autologous Hematopoietic Stem and Progenitor Cells (HSPC)

ACTIVE NOT RECRUITING
NCT06155500Phase PHASE1Novartis PharmaceuticalsStarted 2024-04-16
OTQ923
Sickle Cell DiseaseHydroxyurea FailureHydroxyurea Intolerance

Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Severe Sickle Cell Disease (SCD)

ACTIVE NOT RECRUITING
NCT05329649Phase PHASE3Vertex Pharmaceuticals IncorporatedStarted 2022-05-02
CTX001
Beta-ThalassemiaThalassemiaHematologic Diseases

Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease

RECRUITING
NCT05477563Phase PHASE3Vertex Pharmaceuticals IncorporatedStarted 2022-08-02
CTX001
Beta-Thalassemia

Safety and Efficacy Evaluation of BRL-101 in Subjects With Transfusion-Dependent β-Thalassemia

ENROLLING BY INVITATION
NCT05577312Phase PHASE1, PHASE2Bioray LaboratoriesStarted 2022-11-01
BRL-101
Sickle Cell DiseaseSickle Cell Anemia (HbSS, or HbSβ-thalassemia0)Beta-Thalassemia

Hematopoietic Stem Cell BCL11A Enhancer Gene Editing for Severe β-Hemoglobinopathies

RECRUITING
NCT06647979Phase PHASE1Daniel BauerStarted 2025-12-01
autologous bone marrow derived CD34+ HSPCs electroporated with BCL11A enhancer targeting Cas9 ribonucleoproteinSequencing Assay for Variant rs114518452
Sickle Cell Disease

Gene Transfer for Sickle Cell Disease

ACTIVE NOT RECRUITING
NCT03282656Phase PHASE1David WilliamsStarted 2018-02-13
single infusion of autologous bone marrow derived CD34+ HSC cells transduced with the lentiviral vector containing a short-hairpin RNA targeting BCL11a
Fetal HemoglobinThalassemia MajorGenetic Disease

Unraveling the Impact of Thalidomide at Diverse Doses in Transfusion Dependent Beta Thalassemia

RECRUITING
NCT06490627Phase PHASE2National Institute of Blood and Marrow Transplant (NIBMT), PakistanStarted 2024-04-22
ThalidomideThalidomide