Mechanisms linking mutations in the EKLF/KLF1 gene with the impact that they have on erythrocyte phenotypes. The flow of gene expression from each of the 2 EKLF/KLF1 alleles at the top is shown as it progresses through transcript and protein expression, ultimately leading to the resultant phenotype and disorder as described in “EKLF mutations related to hematologic parameters and disease.” Selected examples from Table 1 are shown at the bottom that illustrate each mechanistic subtype. (A) A mutation (red) changes a functionally important amino acid (aa) and leads to an EKLF protein with altered properties that even in the presence of the WT allele causes a dominant mutant phenotype on a select subset of target genes. (B) Haploinsufficiency of EKLF follows as a consequence of: B(1), a mutation (green) that causes a premature stop codon in one allele, and the defective transcript undergoes nonsense mediated decay, leaving transcript from only a single WT allele to be translated into functional protein; B(2), a mutation (yellow) changes a structurally important amino acid and results in expression of a functionally impaired protein that decreases the pool of active EKLF to haploinsufficient levels. Positions of the mutations in the schematic are symbolic and do not relate to any precise amino acids.