Krüppel‐like factor 1: hematologic phenotypes associated with KLF1 gene mutations

Krüppel-like factor 1 (KLF1) is a pleiotropic erythroid transcription factor that is essential for hematopoiesis. KLF1 mutations have been associated with severe hematologic disorders, including congenital dyserythropoietic anemia type IV (CDAN4) due to a dominant-negative missense mutation (c.973G>A, p.Glu325Lys) and transfusion-dependent hemolytic anemia in compound heterozygotes for loss-of-function mutations. In addition, several benign hematologic conditions are due to KLF1 haploinsufficiency. Herein, we review the genotype-phenotype relationship associated with KLF1 mutations and discuss the utility of KLF1 gene testing in laboratory hematology.