Histone lysine acetyltransferase 6A (KAT6A)

Histone lysine acetyltransferase 6A (KAT6A), also known as MOZ or MYST3, is a member of the MYST family of histone acetyltransferases that plays a critical role in epigenetic regulation [UniProt, 2024]. It functions as the catalytic subunit of a multi-protein complex (including BRPF1/2/3, ING5, and MEAF6) that acetylates lysine residues on histone H3, particularly H3K9, H3K14, and H3K23, thereby promoting an open chromatin state and activating gene transcription [NIH, 2023]. KAT6A is essential for normal development, including hematopoiesis and neurodevelopment, and its dysregulation is linked to several human diseases [Wikipedia, 2024]. In oncology, KAT6A is frequently involved in chromosomal translocations in acute myeloid leukemia (AML) and is amplified or overexpressed in approximately 15% of estrogen receptor-positive (ER+) breast cancers, where it drives oncogenic signaling [Nature, 2023]. Therapeutic strategies focus on small-molecule inhibitors, such as PF-07248144 and PF-9363, which target the catalytic domain to suppress tumor growth by inducing cellular senescence or inhibiting ER-driven gene expression [ClinicalTrials.gov, 2024]. Beyond cancer, germline mutations in KAT6A cause Arboleda-Tham syndrome, a neurodevelopmental disorder characterized by intellectual disability and cardiac anomalies [NIH, 2025].

Other names

MOZMYST3RUNXBP2ZC2HC6AZNF220MRD32MYST-3ARTHSMonocytic leukemia zinc finger protein

Small molecule inhibition of the KAT6A/B catalytic MYST domain, which prevents the acetylation of histone H3 (specifically H3K23), leading to chromatin condensation, downregulation of oncogenic transcription factors (such as ER and Myc), and induction of cellular senescence [NIH, 2023; Nature, 2023].