SET domain containing 1A, histone lysine methyltransferase (SETD1A)

SET domain containing 1A, histone lysine methyltransferase (SETD1A) is a nuclear enzyme that catalyzes mono-, di-, and trimethylation of lysine 4 on histone H3 (H3K4), a chromatin mark associated with transcriptional activation[1][2][3][4]. SETD1A functions as the principal catalytic subunit of the COMPASS complex in mammals, which coordinates histone methylation and gene expression regulation at active promoters[2][4]. It contains SET, post-SET, and RNA recognition motifs, and its activity is tightly regulated by interactions with other proteins (including WRAD, CFP1, WDR82, HCF1)[1][2][3]. SETD1A controls key processes such as DNA damage repair, cell cycle progression, neural progenitor proliferation/differentiation, and embryonic development[1][2][4]. Dysfunction or mutation of SETD1A causes neurodevelopmental disorders (developmental delay, intellectual disability), is linked to schizophrenia and epilepsy, and contributes to genome instability associated with tumorigenesis[2][3][4]. While no approved drugs currently target SETD1A directly, it is a focus of therapeutic research in cancer and neuropsychiatric diseases due to its epigenetic regulatory function[2][4].

Other names

KMT2FSET1AhSET1AKIAA0339Lysine N-methyltransferase 2FSET domain-containing protein 1ASet1Set1ASet1/Ash2 histone methyltransferase complex subunit SET1EPEDDEPEO2NEDSID

Inhibition of methyltransferase activity: Small molecules that inhibit the enzymatic function of SETD1A would decrease H3K4 methylation, altering gene expression. Modulation of COMPASS complex assembly: Agents influencing complex formation or protein-protein interactions may affect SETD1A activity. Targeting associated pathways: Modulation of downstream pathways (e.g., Wnt/β-catenin, cell cycle) through SETD1A-related network regulation.