SETD1A

SETD1A
Identifiers
Aliases	SETD1A, KMT2F, Set1, Set1A, SET domain containing 1A, SET domain containing 1A, histone lysine methyltransferase, EPEDD, NEDSID
External IDs	OMIM: 611052; MGI: 2446244; GeneCards: SETD1A
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3S8S, 3UVN, 4EWR
Enzyme activity
Gene location (Human)
Chr.	Chromosome 16 (human)
End	30,984,664 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	127,399,294 bp
RNA expression pattern
	Top expressed in
	paraflocculus of cerebellum; ; sural nerve; ; parotid gland; ; middle frontal gyrus; ; Brodmann area 10; ; right testis; ; left testis; ; dorsal motor nucleus of vagus nerve; ; granulocyte; ; gastrocnemius muscle;
	Top expressed in
	tail of embryo; ; genital tubercle; ; secondary oocyte; ; zygote; ; Rostral migratory stream; ; tibiofemoral joint; ; neural layer of retina; ; cumulus cell; ; muscle of thigh; ; ventricular zone;
	More reference expression data
	n/a
Gene ontology
Molecular function	methyltransferase activity; transferase activity; beta-catenin binding; protein binding; RNA binding; nucleic acid binding; histone-lysine N-methyltransferase activity; transcription factor binding; histone methyltransferase activity (H3-K4 specific); euchromatin binding;
Cellular component	chromosome; nucleus; histone methyltransferase complex; nucleoplasm; nuclear speck; Set1C/COMPASS complex;
Biological process	regulation of transcription, DNA-templated; transcription, DNA-templated; methylation; histone H3-K4 methylation; regulation of hematopoietic stem cell differentiation; regulation of megakaryocyte differentiation; histone lysine methylation; regulation of chromatin organization; chromatin organization; positive regulation of gene expression; stem cell population maintenance; regulation of erythrocyte differentiation; positive regulation of neural precursor cell proliferation; positive regulation of stem cell proliferation;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	9739
	233904
	ENSG00000099381
	ENSMUSG00000042308
	O15047
	E9PYH6
	NM_014712
	NM_010940; NM_178029
	NP_055527
	NP_821172
	Wikidata
View/Edit Human	View/Edit Mouse

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.

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.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000099381 – Ensembl, May 2017
1 2 3 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.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000099381 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000042308 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid32795105-5] 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.

[pmid32346159-6] 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.

[pmid31197650-7] 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.

[pmid29923609-8] 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.

[9] 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.

[10] 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.

[11] 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.

SETD1A

Clinical significance

History

See also

References