SET domain containing protein 1A

SET domain containing protein 1A (SETD1A) is a protein that serves as a component of a histone methyltransferase (HMT) complex that produces mono-, di-, and trimethylated histone H3 at the lys4 residue (K4). SETD1A is highly homologous with SETDB1 but has a distinct subnuclear distribution.^[1]

Clinical significance

Mutations of the SETD1A gene can cause neurodevelopmental disorder with speech impairment and dysmorphic facies (NEDSID) discovered in 2021,^[2] and early-onset epilepsy with or without developmental delay, first described in 2019.^[3]

According to a review published in 2018, mutations of the SETD1A gene may increase the risk of schizophrenia, based on studies available up to that date.^[4] A later review from 2024 found that SETD1A mutations been associated with development of schizophrenia at a later age.^[5] Loss of function (LoF) variants in SETD1A and epigenetic dysregulations of the gene are therefore thought to play an important role in the pathogenesis of schizophrenia.^[6]

History

The protein was first described in man in 2003 by Wysocka et al.^[7]

See also

• SETDB1 - highly homologous to SETD1A
• SET domain