GATA1 (GATA binding protein 1 (globin transcription factor1))

2019-07-01   Winston Y. Lee , Olga K. Weinberg 

Lee, WY : Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, (WYL); Department of Pathology, Brigham and Womens Hospital, Harvard Medical School, Boston, MA, (OKW) USA




We provide a survey of the disease entities associated with GATA1 mutations.



Genomic sequence 7,757 bases, mRNA six exons (five coding); Plus strand


mRNA 1497bp


Atlas Image
Alternative models for generation of GATA1 isoforms. The full GATA1 protein can only be translated from the full GATA1 mRNA, whereas the GATA1s protein can be translated either from the full gata-1mRNA or from the shorter splice variant in which exon 2 is skipped.


GATA1 is physiologically present as two protein isoforms that are derived from alternative splicing of the mRNA and the usage of an alternative translation initiation sites as shown in the Figure. The full length GATA1 protein is comprised of 413 amino acids with a predicted molecular weight of 42.7 KDa. The shorter form of the GATA1 protein (GATA1s) lacks the first 83 amino acid residues, which contains the so-called N-terminal activation domain (AD) (Gruber TA et al., 2015). Both proteins contain two Zinc finger domains mediating protein interactions and DNA binding. The expression level and ratio of both GATA1 isoforms are thought to be important in directing the appropriate erythromegakaryocytic development.


Bone marrow: erythroid, megakaryocytic, mast cell and eosonophillic precursors. Testis: Sertoli cells




Transcription Factor, essential for erythroid and megakaryocytic development


A member of the GATA-binding factor (GATA) family.



Implicated dyserythropoietic anemia with thrombocytopenia/ Macrothrombocytopenia. and in Diamond-Blackfan anemia


Myeloid proliferation associated with Down syndrome, including:
  • transient abnormal myelopoiesis associated with Down syndrome, and
  • myeloid leukemia associated with Down syndrome
  • Implicated in

    Acquired somatic mutations resulting in the exclusive production of the short-form GATA1 protein (GATA1s) are pathognomonic in myeloid proliferation associated with Down syndrome (MP-DS) (Ahmed M et al, 2004; Groet J et al, 2003; Rainis L et al, 2003; Wechsler J et al, 2002). These mutations are often in the forms of nonsense or frame-shift mutations that result in premature stop codons in exon 2 or 3, while sparing the alternative start codon further downstream in the exon 3. GATA1 mutations can be detected in umbilical cord blood of DS patients and in fetal liver of aborted DS embryos; therefore, these mutations are thought to occur in-utero, likely during fetal liver hematopoiesis (Ahmed M et al, 2004; Taub JW et al, 2004). The presence of GATA1s in the absence of full length GATA1 is thought to block megakaryocytic differentiation and promote the proliferation of megakaryoblasts (Vyas P et al, 1999; Li Z et al, 2005; Lee WY et al, 2018). This disease entity only occurs in DS patients; however, the genes on chromosome 21 that enables the development of this disease are not known. MP-DS mostly occurs in children with DS younger than 5 years of age and manifests initially as transient abnormal myelopoiesis (TAM) within 7 days of birth. TAM is characterized by increased circulating megakaryocytic blasts, thrombocytopenia, and leukocytosis. The majority of cases of TAM undergo clonal extinction and spontaneously remit. However, about a third of the cases eventually recur within 3 years as myeloid leukemia associated with Down syndrome (ML-DS), which phenotypically resembles acute megakaryocytic leukemia and requires therapy. Next generation sequencing studies comparing the genomic landscape of TAM and ML-DS have established the GATA1 mutations as the first-hit mutations that presents phenotypically as TAM, and the subsequent gain of additional hits leads to the progression as ML-DS (Nikolaev SI et al, 2013; Yoshida K et al, 2013).
    Atlas Image
    Example to the distribution of the mutations in children with M7 and DS described in Rainis et al.
    Entity name
    Diamond-Blackfan anemia
    Diamond-Blackfan anemia (DBA) is a congenital condition characterized by isolated erythroid hypoplasia. Approximately half of the DBA cases are associated with germline mutations that result in haploinsufficiency of ribosomal proteins. A smaller subset of DBA cases, all of which are X-linked, is associated with germline GATA1 mutations, including substitution or splice site mutations involving exon 2 or 3 (Ludwig LS et al, 2014; Parrella S et al, 2014; Klar J et al, 2014; Sankaran VG, 2012). These mutations, similar to those seen in MP-DS (see above), create missense or nonsense mutations at the first start codon or premature stop codons before the second alternative start codon, thereby precluding the production of the full length GATA1 and leading to the exclusive production of the short form of GATA1 (GATA1s). Interestingly, several studies have suggested that in DBA with ribosomal protein haploinsufficiency exhibits altered translation of GATA1 mRNA, providing a possible converging mechanism of DBA (Ludwig LS et al, 2014; Khajuria RK et al, 2018).
    Entity name
    Dyserythropoietic anemia
    Dyserythropoietic anemia (DA), is a rare congenital red blood cell disorder characterized by anemia with erythrodysplasia (often abnormal forms with multinucleated nuclei) and varying degrees of macrothrombocytopenia with dysplastic megakaryocytes. There are several isolated case reports describing the roles of GATA1 mutations in a subset of DA, which often presents as severe fetal anemia requiring intrauterine transfusion (Zucker J et al , 2016; Abdulhay NJ et al, 2019; Kratz CP et al, 2008; Freson K et al, 2002; Nichols KE et al, 2000; Del Vecchio GC et al, 2005). Based on the limited case reports, there appears to be two different classes of GATA1 mutations that can cause DA. The first class of mutations (such as, V205M, G208R, and D218Y/G) appears to affect interaction with FOG-1 (Friends of GATA1), a transcriptional co-factor required for normal erythroid and megakaryocytic differentiation. The second class of mutations appears to affect the splicing of GATA1 transcripts that result in the preferential production of the short form of GATA1 protein, in a similar manner seen in DBA (see above). Mutations altering the pattern of splicing were described to involve the 5 untranslated region and in the fifth intron. Of note, these cases are distinctly different from congenital dyserythropoietic anemia type I, II, and III. Some have proposed to include the GATA1 mutated DA cases as congenital dyserythropoietic anemia variants.


    Pubmed IDLast YearTitleAuthors
    309144382019Impaired human hematopoiesis due to a cryptic intronic GATA1 splicing mutation.Abdulhay NJ et al
    146568752004Natural history of GATA1 mutations in Down syndrome.Ahmed M et al
    161036362005Dyserythropoietic anemia and thrombocytopenia due to a novel mutation in GATA-1.Del Vecchio GC et al
    118097232002Different substitutions at residue D218 of the X-linked transcription factor GATA1 lead to altered clinical severity of macrothrombocytopenia and anemia and are associated with variable skewed X inactivation.Freson K et al
    147447912004The role of cytidine deaminase and GATA1 mutations in the increased cytosine arabinoside sensitivity of Down syndrome myeloblasts and leukemia cell lines.Ge Y et al
    127478842003Acquired mutations in GATA1 in neonates with Down's syndrome with transient myeloid disorder.Groet J et al
    261869392015The biology of pediatric acute megakaryoblastic leukemia.Gruber TA et al
    145123212004Recent insights into the mechanisms of myeloid leukemogenesis in Down syndrome.Gurbuxani S et al
    150707112004The GATA1 mutation in an adult patient with acute megakaryoblastic leukemia not accompanying Down syndrome.Harigae H et al
    156304112005Origins of leukaemia in children with Down syndrome.Hitzler JK et al
    239402842013Congenital dyserythropoietic anemias: molecular insights and diagnostic approach.Iolascon A et al
    151987272004Leukaemia -- a developmental perspective.Izraeli S et al
    295512692018Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis.Khajuria RK et al
    247662962014Recurrent GATA1 mutations in Diamond-Blackfan anaemia.Klar J et al
    177135522008Congenital transfusion-dependent anemia and thrombocytopenia with myelodysplasia due to a recurrent GATA1(G208R) germline mutation.Kratz CP et al
    294815792018Loss of Full-Length GATA1 Expression in Megakaryocytes Is a Sensitive and Specific Immunohistochemical Marker for the Diagnosis of Myeloid Proliferative Disorder Related to Down Syndrome.Lee WY et al
    158950802005Developmental stage-selective effect of somatically mutated leukemogenic transcription factor GATA1.Li Z et al
    121725492002A leukemogenic twist for GATA1.Look AT et al
    249526482014Altered translation of GATA1 in Diamond-Blackfan anemia.Ludwig LS et al
    107001802000Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1.Nichols KE et al
    237333392013Exome sequencing identifies putative drivers of progression of transient myeloproliferative disorder to AMKL in infants with Down syndrome.Nikolaev SI et al
    244530672014Loss of GATA-1 full length as a cause of Diamond-Blackfan anemia phenotype.Parrella S et al
    126491312003Mutations in exon 2 of GATA1 are early events in megakaryocytic malignancies associated with trisomy 21.Rainis L et al
    227063012012Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia.Sankaran VG et al
    153177362004Prenatal origin of GATA1 mutations may be an initiating step in the development of megakaryocytic leukemia in Down syndrome.Taub JW et al
    102160811999Consequences of GATA-1 deficiency in megakaryocytes and platelets.Vyas P et al
    121725472002Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome.Wechsler J et al
    240567182013The landscape of somatic mutations in Down syndrome-related myeloid disorders.Yoshida K et al
    267134102016A Child With Dyserythropoietic Anemia and Megakaryocyte Dysplasia Due to a Novel 5'UTR GATA1s Splice Mutation.Zucker J et al

    Other Information

    Locus ID:

    NCBI: 2623
    MIM: 305371
    HGNC: 4170
    Ensembl: ENSG00000102145


    dbSNP: 2623
    ClinVar: 2623
    TCGA: ENSG00000102145


    Gene IDTranscript IDUniprot

    Expression (GTEx)



    PathwaySourceExternal ID
    Factors involved in megakaryocyte development and platelet productionREACTOMER-HSA-983231

    Protein levels (Protein atlas)

    Not detected


    Pubmed IDYearTitleCitations
    121725472002Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome.181
    128579542003GATA-1-dependent transcriptional repression of GATA-2 via disruption of positive autoregulation and domain-wide chromatin remodeling.162
    156843762005GATA1 function, a paradigm for transcription factors in hematopoiesis.129
    227063012012Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia.122
    215712182011Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators.116
    125763322003RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation.103
    249526482014Altered translation of GATA1 in Diamond-Blackfan anemia.102
    158950802005Developmental stage-selective effect of somatically mutated leukemogenic transcription factor GATA1.99
    171674222007Hsp70 regulates erythropoiesis by preventing caspase-3-mediated cleavage of GATA-1.80
    267664402016Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis.70


    Winston Y. Lee ; Olga K. Weinberg

    GATA1 (GATA binding protein 1 (globin transcription factor1))

    Atlas Genet Cytogenet Oncol Haematol. 2019-07-01

    Online version:

    Historical Card

    2005-02-01 GATA1 (GATA binding protein 1 (globin transcription factor1)) by  Shai Izraeli 

    Pediatric Hemato-Oncology, Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel 52621