MLL2

MLL2 is a historical name for a human gene now commonly referred to as KMT2D (lysine methyltransferase 2D). The MLL2 designation reflects its membership in the mixed-lineage leukemia (MLL) family of histone methyltransferases. The gene encodes a large nuclear enzyme that contains a catalytic SET domain and mediates methylation of histone H3 on lysine 4 (H3K4), a modification associated with active transcription.

Biological role and molecular function: MLL2/KMT2D is part of COMPASS-like multi-subunit complexes that regulate gene expression during development and differentiation. It participates in establishing and maintaining transcriptional programs by depositing H3K4 methyl marks at promoter and regulatory regions of target genes. Its activity is often coordinated with core components such as WDR5, ASH2L, RbBP5, and DPY30, among others, enabling proper chromatin remodeling and gene activation.

Clinical significance: Germline mutations in KMT2D (historically MLL2) cause Kabuki syndrome type 1, a congenital disorder characterized by distinctive facial features, growth delay, and developmental anomalies. The gene can also acquire somatic alterations in various cancers, where changes in H3K4 methylation contribute to altered transcriptional landscapes and tumor biology.

Nomenclature and history: The alias MLL2 reflects early naming within the MLL gene family. With standardized gene symbols, the official name is KMT2D, though the historical term MLL2 remains widely encountered in older literature and some research contexts.

See also: Kabuki syndrome, COMPASS complex, histone methyltransferases, KMT2D.