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.

Clinical significance

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

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. A later review from 2024 found that SETD1A mutations been associated with development of schizophrenia at a later age. 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.

History

The protein was first described in man in 2003 by Wysocka et al.

See also

• SETDB1 - highly homologous to SETD1A
• SET domain