ClinGen Dosage Sensitivity Curation Page

GATA1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

GATA1 variants can result in a variety of related disease, characterized by thrombocytopenia and/or anemia. The majority of reported variants are missense variants, with some reported splicing variants. There have been no whole gene deletions of GATA1 reported. Campbell et al. 2013 (PMID 23704091) analyzed a few patients missense variants in GATA1 and suggested that mechanism was by LOF. Splice site variants have been shown to result in the production of an abnormal short form of the protein. Therefore while the mechanism may be LOF, there is no evidence of disease due to haploinsufficiency. Sankaran et al. 2012 (PMID 22706301) - boy with anemia with a 1bp deletion (332delG), predicted to impair splicing and frameshift of the full-length open reading frame. This defect lead to impaired production of the full-length form of the protein. Zucker et al. 2016 (PMID 26713410)- child with thrombocytopeniawith a germline mutation in the 5'UTR which impaired a 5'UTR splicing site, leading to the production of the shortened GATA1 isoform.

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

no evidence for triplosensitivity

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.