HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
BCL11A
BCL11 transcription factor A
Chromosome 2 Β· 2p16.1
NCBI Gene: 53335Ensembl: ENSG00000119866.22HGNC: HGNC:13221UniProt: A0A2R8Y2E8
189PubMed Papers
21Diseases
1Drugs
92Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneTranscription Factor
RESEARCH IMPACT
Variant-Rich
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
nuclear bodySWI/SNF complexnucleoplasmRNA polymerase II cis-regulatory region sequence-specific DNA bindingDias-Logan syndromeIntellectual disabilitybenign prostatic hyperplasiagenetic disorder
✦AI Summary

BCL11A is a transcription factor that binds the DNA motif 5'-TGACCA-3' in regulatory regions and associates with the BAF SWI/SNF chr2 remodeling complex 123. Its primary function is repression of fetal hemoglobin (HbF) through direct repression of the HBG1 gamma-globin gene, regulating the developmental switch from fetal to adult hemoglobin 42. BCL11A operates specifically through an erythroid-specific enhancer region containing critical GATA1 binding sites 56. Clinically, BCL11A mutations cause intellectual developmental disorder with persistence of fetal hemoglobin. More significantly, BCL11A has become a major therapeutic target for sickle cell disease (SCD) and transfusion-dependent Ξ²-thalassemia (TDT). CRISPR-Cas9 editing of the BCL11A erythroid enhancer in autologous CD34+ hematopoietic stem cells reactivates HbF production, achieving clinical benefits: 97% of SCD patients achieved freedom from vaso-occlusive crises for β‰₯12 months 7, while 91% of TDT patients achieved transfusion independence with sustained hemoglobin levels of 13.1 g/dL 8. Both therapies demonstrated excellent safety profiles with no off-target editing detected and no cancer development 95.

Sources cited
1
BCL11A functions as a transcription factor
PMID: 16704730
2
BCL11A binds 5'-TGACCA-3' sequence motif and directly represses HBG1 to regulate fetal hemoglobin
PMID: 29606353
3
BCL11A associates with the BAF SWI/SNF chromatin remodeling complex
PMID: 23644491
4
BCL11A regulates the developmental switch from gamma- to beta-globin via repression of HBG1
PMID: 26375765
5
CRISPR-Cas9 editing at the BCL11A erythroid enhancer GATA1 site induces fetal hemoglobin in patient-derived hematopoietic stem cells with high efficiency and no genotoxicity
PMID: 30911135
6
BCL11A has an erythroid-specific enhancer with critical primate-specific sequences subject to common genetic variation
PMID: 26375006
7
BCL11A editing therapy (exa-cel) achieved 97% freedom from vaso-occlusive crises in sickle cell disease patients for β‰₯12 months
PMID: 38661449
8
BCL11A editing therapy achieved 91% transfusion independence in Ξ²-thalassemia patients with mean hemoglobin 13.1 g/dL
PMID: 38657265
9
CRISPR-Cas9 targeting of BCL11A enhancer achieved ~80% allelic modification with no off-target editing and clinical efficacy in sickle cell and Ξ²-thalassemia patients
PMID: 33283989
Disease Associationsβ“˜21
Dias-Logan syndromeOpen Targets
0.79Strong
Intellectual disabilityOpen Targets
0.66Moderate
benign prostatic hyperplasiaOpen Targets
0.52Moderate
genetic disorderOpen Targets
0.51Moderate
cancerOpen Targets
0.51Moderate
intelligenceOpen Targets
0.51Moderate
schizophreniaOpen Targets
0.49Moderate
sickle cell diseaseOpen Targets
0.47Moderate
mathematical abilityOpen Targets
0.46Moderate
Neurodevelopmental delayOpen Targets
0.44Moderate
COVID-19Open Targets
0.43Moderate
lower urinary tract symptomOpen Targets
0.42Moderate
neurodegenerative diseaseOpen Targets
0.42Moderate
Beta-thalassemiaOpen Targets
0.40Weak
risk-taking behaviourOpen Targets
0.39Weak
ThalassemiaOpen Targets
0.38Weak
breast ductal adenocarcinomaOpen Targets
0.37Weak
Endometrial Endometrioid AdenocarcinomaOpen Targets
0.37Weak
esophageal adenocarcinomaOpen Targets
0.37Weak
nodular melanomaOpen Targets
0.37Weak
Intellectual developmental disorder with persistence of fetal hemoglobinUniProt
Pathogenic Variants92
NM_022893.4(BCL11A):c.1417G>T (p.Glu473Ter)Pathogenic
Dias-Logan syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 473
NM_022893.4(BCL11A):c.1078del (p.Leu360fs)Pathogenic
not provided|Dias-Logan syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 360
NM_022893.4(BCL11A):c.1078dup (p.Leu360fs)Pathogenic
not provided|Dias-Logan syndrome|Neurodevelopmental delay|See cases
β˜…β˜…β˜†β˜†2025β†’ Residue 360
NM_022893.4(BCL11A):c.793dup (p.Leu265fs)Pathogenic
not provided|Inborn genetic diseases|Dias-Logan syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 265
NM_022893.4(BCL11A):c.1118dup (p.Val374fs)Pathogenic
Dias-Logan syndrome|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 374
NM_022893.4(BCL11A):c.1847del (p.Gly616fs)Likely pathogenic
Dias-Logan syndrome|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 616
NM_022893.4(BCL11A):c.488-1G>APathogenic
Dias-Logan syndrome
β˜…β˜…β˜†β˜†2024
NM_022893.4(BCL11A):c.1A>G (p.Met1Val)Pathogenic
Dias-Logan syndrome|Neurodevelopmental delay
β˜…β˜…β˜†β˜†2021β†’ Residue 1
NM_022893.4(BCL11A):c.370C>T (p.Gln124Ter)Pathogenic
not provided|Dias-Logan syndrome
β˜…β˜…β˜†β˜†2020β†’ Residue 124
NM_022893.4(BCL11A):c.385+2T>CPathogenic
Inborn genetic diseases|Dias-Logan syndrome
β˜…β˜…β˜†β˜†2018
NM_022893.4(BCL11A):c.28C>T (p.Gln10Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 10
NM_022893.4(BCL11A):c.793_794del (p.Leu265fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 265
NM_022893.4(BCL11A):c.1847dup (p.Leu617fs)Likely pathogenic
Dias-Logan syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 617
NM_022893.4(BCL11A):c.575del (p.Thr192fs)Pathogenic
Dias-Logan syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 192
NM_022893.4(BCL11A):c.793del (p.Leu265fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 265
NM_022893.4(BCL11A):c.384A>G (p.Ala128=)Pathogenic
Dias-Logan syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 128
NM_022893.4(BCL11A):c.174_175dup (p.Asp59fs)Likely pathogenic
Dias-Logan syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 59
NM_022893.4(BCL11A):c.10C>T (p.Arg4Cys)Likely pathogenic
Dias-Logan syndrome|not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 4
NM_022893.4(BCL11A):c.1230C>A (p.Cys410Ter)Likely pathogenic
Dias-Logan syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 410
NM_022893.4(BCL11A):c.1453G>T (p.Glu485Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 485
View on ClinVar β†—
Drug Targets1
EXAGAMGLOGENE AUTOTEMCELApproved
B-cell lymphoma/leukemia 11A gene editing negative modulator
sickle cell disease
Related Genes
HDAC2Protein interaction100%RBBP7Protein interaction100%PHF10Protein interaction99%NR2F2Protein interaction99%SMARCA4Protein interaction98%ARID2Protein interaction97%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
13%
Heart
8%
Lung
1%
Liver
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
BCL11AHDAC2RBBP7PHF10NR2F2SMARCA4ARID2
PROTEIN STRUCTURE
Preparing viewer…
PDB6U9Q Β· 1.83 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.13Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.04 [0.01–0.13]
RankingsWhere BCL11A stands among ~20K protein-coding genes
  • #2,262of 20,598
    Most Researched189 Β· top quartile
  • #875of 1,025
    FDA-Approved Drug Targets1
  • #831of 5,498
    Most Pathogenic Variants92 Β· top quartile
  • #123of 17,882
    Most Constrained (LOEUF)0.13 Β· top 1%
Genes detectedBCL11A
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
CRISPR-Cas9 Gene Editing for Sickle Cell Disease and Ξ²-Thalassemia.
PMID: 33283989
N Engl J Med Β· 2021
1.00
2
Exagamglogene Autotemcel for Severe Sickle Cell Disease.
PMID: 38661449
N Engl J Med Β· 2024
0.90
3
Sickle Cell Anemia and Its Phenotypes.
PMID: 29641911
Annu Rev Genomics Hum Genet Β· 2018
0.80
4
Exagamglogene Autotemcel for Transfusion-Dependent Ξ²-Thalassemia.
PMID: 38657265
N Engl J Med Β· 2024
0.70
5
Post-Transcriptional Genetic Silencing of
PMID: 33283990
N Engl J Med Β· 2021
0.68