KLF1 Gene - Erythroid Kruppel-like Factor 1 | Function, Mutations & Diseases

KLF1 (Kruppel-like factor 1, also known as EKLF) is a zinc-finger transcription factor essential for erythroid development and differentiation. It directly activates beta-globin gene expression and regulates the switch from fetal (gamma) to adult (beta) hemoglobin. KLF1 also controls expression of many erythroid-specific genes involved in membrane stability, heme synthesis, and cell cycle regulation. Loss-of-function mutations cause congenital dyserythropoietic anemia type IV and the In(Lu) blood group phenotype, while gain-of-function variants are associated with hereditary persistence of fetal hemoglobin (HPFH).

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Erythropoiesis (Reactome: R-HSA-1266738)

• Hemoglobin switching (Reactome: R-HSA-983231)

• Transcriptional regulation by KLF1 (Reactome: R-HSA-983232)

KLF1 (EKLF) is a 362-amino acid zinc-finger transcription factor that binds to CACCC boxes in the beta-globin locus control region and promoters. It is essential for definitive erythropoiesis, activating beta-globin and repressing gamma-globin expression. The protein contains three C-terminal C2H2 zinc fingers that mediate DNA binding and an N-terminal transactivation domain. Post-translational modifications include acetylation and phosphorylation, which modulate its activity. KLF1 also interacts with chromatin remodeling complexes (e.g., SWI/SNF) to regulate erythroid gene expression.