GeneID: 15


Common Name: BCL11A Type: Gene
Chromosome: 2 (NC_000002.12) Locus: NG_011968.1 (BCL11A)
HUGO Symbol: BCL11A Full Name: B-cell CLL/lymphoma 11A
Exons: 5 Introns: 4

This gene encodes a C2H2 type zinc-finger protein of which expression is downregulated during haematopoietic cell differentiation. 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. Abundant expression of full-length forms of BCL11A is developmentally restricted to adult erythroid cells. Downregulation of BCL11A expression in primary adult erythroid cells lead to robust fetal haemoglobin (HbF) expression. Consistent with its direct role in globin gene regulation, BCL11A occupies several discrete sites in the beta-globin gene cluster. Genetic variation in BCL11A gene on chromosome 2p15 underlies the HbF quantitative trait locus, accounting for approximately 15.1% of the trait variance. The strongest associations for genome-wide variants are located in a region spanning 14 kb in the second intron of the BCL11A gene. It exhibited strong association with HbF levels and with quantitative variation in the production of F cells (erythrocytes containing measurable amounts of HbF). BCL11A binds the γ-globin gene proximal promoters to a region at –115 bp upstream of the transcription start site. The TGACCA motif emerged as the preferred binding site of BCL11A and its recognition is mediated through zinc finger ZnF456. HPFH-associated substitutions, such as -114, -115 and -117 disrupt binding of BCL11A to the γ-globin gene promoters.

Synonyms: BCL11A-L , BCL11A-S , BCL11A-XL , CTIP1 , HBFQTL5 , ZNF856 , EVI9


Sequence Viewer

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Publications / Origin

  1. Satterwhite E, Sonoki T, Willis TG, Harder L, Nowak R, Arriola EL, Liu H, Price HP, Gesk S, Steinemann D, Schlegelberger B, Oscier DG, Siebert R, Tucker PW, Dyer MJ, The BCL11 gene family: involvement of BCL11A in lymphoid malignancies., Blood , 98(12), 3413-20, 2001 PubMed
  2. Menzel S, Garner C, Gut I, Matsuda F, Yamaguchi M, Heath S, Foglio M, Zelenika D, Boland A, Rooks H, Best S, Spector TD, Farrall M, Lathrop M, Thein SL, A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15., Nat. Genet. , 39(10), 1197-9, 2007 PubMed
  3. Uda M, Galanello R, Sanna S, Lettre G, Sankaran VG, Chen W, Usala G, Busonero F, Maschio A, Albai G, Piras MG, Sestu N, Lai S, Dei M, Mulas A, Crisponi L, Naitza S, Asunis I, Deiana M, Nagaraja R, Perseu L, Satta S, Cipollina MD, Sollaino C, Moi P, Hirschhorn JN, Orkin SH, Abecasis GR, Schlessinger D, Cao A, Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia., Proc. Natl. Acad. Sci. U.S.A. , 105(5), 1620-5, 2008 PubMed
  4. Sankaran VG, Menne TF, Xu J, Akie TE, Lettre G, Van Handel B, Mikkola HK, Hirschhorn JN, Cantor AB, Orkin SH, Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A., Science , 322(5909), 1839-42, 2008 PubMed
  5. Martyn GE, Wienert B, Yang L, Shah M, Norton LJ, Burdach J, Kurita R, Nakamura Y, Pearson RCM, Funnell APW, Quinlan KGR, Crossley M, Natural regulatory mutations elevate the fetal globin gene via disruption of BCL11A or ZBTB7A binding., Nat. Genet. , 50(4), 498-503, 2018 PubMed
  6. Liu N, Hargreaves VV, Zhu Q, Kurland JV, Hong J, Kim W, Sher F, Macias-Trevino C, Rogers JM, Kurita R, Nakamura Y, Yuan GC, Bauer DE, Xu J, Bulyk ML, Orkin SH, Direct Promoter Repression by BCL11A Controls the Fetal to Adult Hemoglobin Switch., Cell, 173(2), 430-442.e17, 2018 PubMed
  7. Weber L, Frati G, Felix T, Hardouin G, Casini A, Wollenschlaeger C, Meneghini V, Masson C, De Cian A, Chalumeau A, Mavilio F, Amendola M, Andre-Schmutz I, Cereseto A, El Nemer W, Concordet JP, Giovannangeli C, Cavazzana M, Miccio A, Editing a γ-globin repressor binding site restores fetal hemoglobin synthesis and corrects the sickle cell disease phenotype., Sci Adv . , 6(7), 0, 2020 PubMed
Created on 2014-04-01 14:19:10, Last reviewed on 2020-10-08 13:53:42 (Show full history)

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