SETD1A
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.[5]
Clinical significance
Mutations of the SETD1A gene can cause neurodevelopmental disorder with speech impairment and dysmorphic facies (NEDSID) discovered in 2021,[6] and early-onset epilepsy with or without developmental delay, first described in 2019.[7]
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.[8] A later review from 2024 found that SETD1A mutations been associated with development of schizophrenia at a later age.[9] 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.[10]
History
The protein was first described in man in 2003 by Wysocka et al.[11]
See also
- Methyllysine
- SETDB1 - highly homologous to SETD1A
- SET domain
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000099381 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000042308 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Sugeedha J, Gautam J, Tyagi S (May 2021). "SET1/MLL family of proteins: functions beyond histone methylation". Epigenetics. 16 (5): 469–487. doi:10.1080/15592294.2020.1809873. PMC 8078731. PMID 32795105.
- ^ Kummeling J, Stremmelaar DE, Raun N, Reijnders MR, Willemsen MH, Ruiterkamp-Versteeg M, Schepens M, Man CC, Gilissen C, Cho MT, McWalter K, Sinnema M, Wheless JW, Simon ME, Genetti CA, Casey AM, Terhal PA, van der Smagt JJ, van Gassen KL, Joset P, Bahr A, Steindl K, Rauch A, Keller E, Raas-Rothschild A, Koolen DA, Agrawal PB, Hoffman TL, Powell-Hamilton NN, Thiffault I, Engleman K, Zhou D, Bodamer O, Hoefele J, Riedhammer KM, Schwaibold EM, Tasic V, Schubert D, Top D, Pfundt R, Higgs MR, Kramer JM, Kleefstra T (June 2021). "Characterization of SETD1A haploinsufficiency in humans and Drosophila defines a novel neurodevelopmental syndrome" (PDF). Molecular Psychiatry. 26 (6): 2013–24. doi:10.1038/s41380-020-0725-5. PMID 32346159. S2CID 212792900.
- ^ Yu X, Yang L, Li J, Li W, Li D, Wang R, Wu K, Chen W, Zhang Y, Qiu Z, Zhou W (December 2019). "De Novo and Inherited SETD1A Variants in Early-onset Epilepsy". Neuroscience Bulletin. 35 (6): 1045–57. doi:10.1007/s12264-019-00400-w. PMC 6864154. PMID 31197650.
- ^ Coelewij L, Curtis D (September 2018). "Mini-review: Update on the genetics of schizophrenia". Annals of Human Genetics. 82 (5): 239–243. doi:10.1111/ahg.12259. PMID 29923609. S2CID 49311660.
- ^ Colijn MA, Carrion P, Poirier-Morency G, Rogic S, Torres I, Menon M, Lisonek M, Cook C, DeGraaf A, Thammaiah SP, Neelakant H, Willaeys V, Leonova O, White RF, Yip S, Mungall AJ, MacLeod PM, Gibson WT, Sullivan PF, Honer WG, Pavlidis P, Stowe RM (February 2024). "SETD1A variant-associated psychosis: A systematic review of the clinical literature and description of two new cases". Prog Neuropsychopharmacol Biol Psychiatry. 129 110888. doi:10.1016/j.pnpbp.2023.110888. PMID 37918557.
- ^ Singh T, Kurki MI, Curtis D, Purcell SM, Crooks L, McRae J, Suvisaari J, Chheda H, Blackwood D, Breen G, Pietiläinen O, Gerety SS, Ayub M, Blyth M, Cole T, Collier D, Coomber EL, Craddock N, Daly MJ, Danesh J, DiForti M, Foster A, Freimer NB, Geschwind D, Johnstone M, Joss S, Kirov G, Körkkö J, Kuismin O, Holmans P, Hultman CM, Iyegbe C, Lönnqvist J, Männikkö M, McCarroll SA, McGuffin P, McIntosh AM, McQuillin A, Moilanen JS, Moore C, Murray RM, Newbury-Ecob R, Ouwehand W, Paunio T, Prigmore E, Rees E, Roberts D, Sambrook J, Sklar P, St Clair D, Veijola J, Walters JT, Williams H, Sullivan PF, Hurles ME, O'Donovan MC, Palotie A, Owen MJ, Barrett JC (April 2016). "Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders". Nat Neurosci. 19 (4): 571–7. doi:10.1038/nn.4267. PMC 6689268. PMID 26974950.
- ^ Wysocka J, Myers MP, Laherty CD, Eisenman RN, Herr W (April 2003). "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. doi:10.1101/gad.252103. PMC 196026. PMID 12670868.