• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
GATA2 (HGNC:4171) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
GATA binding protein 2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
NFE1B
%HI
1.46(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.98(Read more about gnomAD pLI score)
LOEUF
0.29(Read more about gnomAD LOEUF score)
Cytoband
3q21.3
Genomic Coordinates
GRCh37/hg19: chr3:128198265-128212044 NCBI Ensembl UCSC
GRCh38/hg38: chr3:128479422-128493201 NCBI Ensembl UCSC
MANE Select Transcript
NM_032638.5 ENST00000341105.7 (Read more about MANE Select)
MANE Plus Clinical Transcript(s)
NM_001145661.2 ENST00000487848.6 (Read more about MANE Plus Clinical)
Function
Transcriptional activator which regulates endothelin-1 gene expression in endothelial cells. Binds to the consensus sequence 5'- AGATAG-3'. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-21996
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
04/12/2023

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 21892158
    Ostergaard et al. (2011): Reported eight mutations of the GATA2 gene which underlies Emberger syndrome, or cause primary lymphedema associated with a predisposition to acute myeloid leukemia (AML). Eight unrelated probands were recruited, one of Chinese ancestry and seven of European ancestry. Two individuals had familial history of primary lymphedema and six were sporadic occurrences. The mutation in both families was frameshift (family 1: p.Leu105ProfsTer15, family 2: p.Arg78ProfsTer107). In the sporadic cases, there were two missense mutations, three frame shift and one nonsense. The proband of Chinese ancestry carried the nonsense mutation (p.Arg337Ter) and had bilateral lower limb and genital lymphedema and myelodysplasia. The probands with frameshift mutations (p.Ala341ProfsTer45, p.Ala341ArgfsTer38, and p.Ala194SerfsTer8) presented with left, bilateral, and right lower limb lymphedema, respectively.
  • PUBMED: 21670465
    Hsu et al. 2011 describe GATA2 variants identified in a cohort of individuals with the monoMAC phenotype, including 4 with insertion/deletion variants (c. 951_952ins, c.778_779ins, c.243_244delAinsGC, c.1–200_871+527del) predicted to result in null alleles because of nonsense mediated decay.
  • PUBMED: 22147895
    Kazenwadel et al (2012) report several patients with familial or sporadic MDS/AML who had GATA2 mutations, including a familial deletion of the first 2 coding exons (c.1-200_871+527del), a frameshift (p.Leu332ThrfsTer53) and splice site variants(c.1017+2T>G) predicted to result in loss of function, and 3 individuals with large contiguous deletions (3q13.33-q21.3 deletion) encompassing the GATA2 gene. The patients with the deletions and frameshift mutations also presented with primary lymphedema.
  • PUBMED: 33759087
    Nakazawa et al 2021 reported a novel 8 nucleotide duplicative insertion at exon 5 (c.1126_1133dup) of the GATA2 gene in a 46 yr old Japanese man with MDS. This variant results in frameshift with early stop codon and in silico analysis confirmed the variant to be deleterious.
  • PUBMED: 34893945
    Jorgensen et al 2022 reported 10 probands in Norway between 2013 and 2020 with germline GATA2 variants. Some of the novel variants reported include: c.1143+5G>A, c.1017+1G>T, c.163C>T p.Gln55Ter, c.1098_1100delGGA, p.Asp367del). This study evaluated the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in GATA2 deficient population using clinical, genetic, and bone marrow characteristics to predict end-point outcome.
  • PUBMED: 34638133
    Singh et al 2021 reported a 3 year old girl with a de novo 187-kb duplication of the entire GATA2 locus. This duplication resulted in lower expression of mRNA and loss of GATA2 protein. They found several fold increase in anti-sense noncoding RNA GATA2-AS1 (RP11-472.220) suggesting the mechanism of action. There was no detection of RNA fusion products as well. This case report reemphasizes the importance of allele count in GATA2 related syndrome
HI Evidence Comments:
Hsu et al. 2013 (PMID:23502222) provide a clear description of the phenotype associated with GATA2 deficiency and the observed mutation spectrum. From their text: "GATA2 deficiency is characterized by monocytopenia; B, natural killer (NK), and dendritic cell lymphopenia; and mycobacterial, fungal, and viral infection. It has been called both MonoMAC, for monocytopenia and Mycobacterium avium complex, and DCML deficiency, for dendritic cell, monocyte, B and NK lymphoid deficiency. Patients may present with myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) or pulmonary alveolar proteinosis. Unlike typical MDS, the marrow in patients with GATA2 deficiency is typically hypocellular and contains atypical and micro-megakaryocytes. Since GATA2 also plays a critical role in the development of the vascular and lymphatic systems, patients may present with lymphedema along with monosomy 7 and MDS, a triad known as Emberger syndrome. The GATA2 mutations reported previously cluster into 2 main groups. Mutations within the highly conserved C-terminal zinc finger include missense changes and deletions that result in loss of the C-terminus. They are predicted to allow production of a stable mRNA that is translated into an abnormal protein. In contrast, the other group of mutations includes full gene deletions, as well as frame shift or early stop mutations, predicted to cause nonsense-mediated decay (NMD) of the mRNA, as reported in both MonoMAC and Emberger syndrome." Of note, in addition to these more classic GATA2 variants, Hsu et al. report on individuals in whom no GATA2 coding region mutations were found, but who had intronic mutations or deletions in conserved enhancers. These patients also presented with monoMAC syndrome, which is characterized by lymphedema, mononuclear cytopenias, recurrent infections, and MDS/AML. Some patients may also be deaf.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000003.11) (NC_000003.12)