MLLT3 Gene: Function, Expression, and Disease Associations

MLLT3 (also known as AF9) encodes a nuclear protein that functions as a component of the super elongation complex (SEC), which facilitates transcriptional elongation by releasing RNA polymerase II from promoter-proximal pausing. The protein contains a YEATS domain that recognizes histone acetylation marks and an AHD (AF9/ENL homology domain) that mediates interactions with DOT1L and other elongation factors. MLLT3 is frequently involved in chromosomal translocations with the MLL gene (KMT2A) in acute leukemias, producing oncogenic fusion proteins that drive aberrant gene expression.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Super elongation complex (SEC) pathway

• MLL (KMT2A) complex-mediated transcriptional regulation

• RNA polymerase II transcription elongation

• HOX gene activation in hematopoiesis

MLLT3 (AF9) is a 568-amino acid nuclear protein that contains an N-terminal YEATS domain (binds acetylated histones) and a C-terminal AHD domain (interacts with DOT1L and ENL). It is a core component of the super elongation complex (SEC), which promotes RNA polymerase II pause release and transcriptional elongation. MLLT3 is essential for normal hematopoiesis and is frequently fused to MLL in acute leukemias via t(9;11). The fusion protein aberrantly recruits DOT1L to MLL target genes, leading to H3K79 methylation and overexpression of leukemogenic genes such as HOXA9 and MEIS1.