Biology:SETD1A
 Generic protein structure example |
Histone-lysine N-methyltransferase 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 lysine 4 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
- Methyllysine
- SETDB1 - highly homologous to SETD1A
- SET domain
References
- ↑ "SET1/MLL family of proteins: functions beyond histone methylation". Epigenetics 16 (5): 469–487. May 2021. doi:10.1080/15592294.2020.1809873. PMID 32795105.
- ↑ "Characterization of SETD1A haploinsufficiency in humans and Drosophila defines a novel neurodevelopmental syndrome". Molecular Psychiatry 26 (6): 2013–24. June 2021. doi:10.1038/s41380-020-0725-5. PMID 32346159. https://www.zora.uzh.ch/id/eprint/192403/1/SETD1A_patients_paper_pre_print_Mol_Psych.pdf.
- ↑ "De Novo and Inherited SETD1A Variants in Early-onset Epilepsy". Neuroscience Bulletin 35 (6): 1045–57. December 2019. doi:10.1007/s12264-019-00400-w. PMID 31197650.
- ↑ "Mini-review: Update on the genetics of schizophrenia". Annals of Human Genetics 82 (5): 239–243. September 2018. doi:10.1111/ahg.12259. PMID 29923609. https://discovery.ucl.ac.uk/id/eprint/10064654/.
- ↑ "SETD1A variant-associated psychosis: A systematic review of the clinical literature and description of two new cases". Prog Neuropsychopharmacol Biol Psychiatry 129. February 2024. doi:10.1016/j.pnpbp.2023.110888. PMID 37918557.
- ↑ "Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders". Nat Neurosci 19 (4): 571–7. April 2016. doi:10.1038/nn.4267. PMID 26974950.
- ↑ "Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1". Genes Dev 17 (7): 896–911. April 2003. doi:10.1101/gad.252103. PMID 12670868.
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