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

Summary 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.