AFF1 Gene: Function, Mutations, and Role in Leukemia

AFF1 (AF4/FMR2 Family Member 1) encodes a nuclear protein that functions as a transcriptional activator and is a component of the super elongation complex (SEC). It is involved in transcriptional elongation by recruiting the positive transcription elongation factor b (P-TEFb) to chromatin. The gene is frequently rearranged in acute lymphoblastic leukemia (ALL) through chromosomal translocations, most commonly t(4;11)(q21;q23), resulting in an MLL-AFF1 fusion protein that drives leukemogenesis. Mutations in AFF1 are also associated with autosomal dominant intellectual disability.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Super elongation complex (SEC)

• Transcriptional elongation by RNA polymerase II

• MLL-AFF1 fusion in acute lymphoblastic leukemia

The AFF1 protein (also known as AF4) is a 1210-amino acid nuclear phosphoprotein that contains an N-terminal homology domain, a nuclear localization signal, and a C-terminal transactivation domain. It interacts with P-TEFb, ELL, and ENL to form the super elongation complex, which promotes RNA polymerase II pause release and transcriptional elongation. In leukemia, the MLL-AFF1 fusion retains the MLL DNA-binding domain and the AFF1 transactivation domain, leading to sustained expression of HOXA9 and MEIS1, which block differentiation.