SETBP1

The gene is located on Chromosome 18, specifically on the long (q) arm of the chromosome at position 12.3. This is also written as 18q12.3.

The SETBP1 gene provides instructions for making a protein known as the SET binding protein 1, which is widely distributed throughout somatic cells. The protein is known to bind to another protein called SET. SETBP1 is a DNA-binding protein that forms part of a group of proteins that act together on histone methylation to make chromatin more accessible and regulate gene expression.{{cite journal | vauthors = Piazza R, Magistroni V, Redaelli S, Mauri M, Massimino L, Sessa A, Peronaci M, Lalowski M, Soliymani R, Mezzatesta C, Pirola A, Banfi F, Rubio A, Rea D, Stagno F, Usala E, Martino B, Campiotti L, Merli M, Passamonti F, Onida F, Morotti A, Pavesi F, Bregni M, Broccoli V, Baumann M, Gambacorti-Passerini C | title = SETBP1 induces transcription of a network of development genes by acting as an epigenetic hub | journal = Nature Communications | volume = 9 | issue = 1 | pages = 2192 | date = June 2018 | pmid = 29875417 | pmc = 5989213 | doi = 10.1038/s41467-018-04462-8 | bibcode = 2018NatCo...9.2192P }} There is still more to learn about the overall function of the SETBP1 protein

and the effect of SET binding.

Gain-of-function mutations in the SETBP1 gene are associated with Schinzel–Giedion syndrome.{{cite journal | vauthors = Acuna-Hidalgo R, Deriziotis P, Steehouwer M, Gilissen C, Graham SA, van Dam S, Hoover-Fong J, Telegrafi AB, Destree A, Smigiel R, Lambie LA, Kayserili H, Altunoglu U, Lapi E, Uzielli ML, Aracena M, Nur BG, Mihci E, Moreira LM, Ferreira VB, Horovitz DD, da Rocha KM, Jezela-Stanek A, Brooks AS, Reutter H, Cohen JS, Fatemi A, Smitka M, Grebe TA, Di Donato N, Deshpande C, Vandersteen A, Lourenço CM, Dufke A, Rossier E, Andre G, Baumer A, Spencer C, McGaughran J, Franke L, Veltman JA, De Vries BB, Schinzel A, Fisher SE, Hoischen A, van Bon BW | title = Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies | journal = PLOS Genetics | volume = 13 | issue = 3 | pages = e1006683 | date = Mar 2017 | doi = 10.1371/journal.pgen.1006683| pmid = 28346496 | pmc = 5386295 | doi-access = free }}

Loss-of-function mutations in the SETBP1 gene are associated with a SETBP1-related developmental delay called SETBP1 disorder which causes a spectrum of symptoms including absent speech/expressive language delays, mild-severe intellectual disability, autistic-traits/autism, developmental delays, ADHD, and seizures.{{cite journal | vauthors = Filges I, Shimojima K, Okamoto N, Röthlisberger B, Weber P, Huber AR, Nishizawa T, Datta AN, Miny P, Yamamoto T | title = Reduced expression by SETBP1 haploinsufficiency causes developmental and expressive language delay indicating a phenotype distinct from Schinzel-Giedion syndrome | journal = Journal of Medical Genetics | volume = 48 | issue = 2 | date = Feb 2011 | pages = 117–22 | pmid = 21037274 | doi = 10.1136/jmg.2010.084582| s2cid = 38823269 }}

{{cite journal | vauthors = Coe BP, Witherspoon K, Rosenfeld JA, van Bon BW, Vulto-van Silfhout AT, Bosco P, Friend KL, Baker C, Buono S, Vissers LE, Schuurs-Hoeijmakers JH, Hoischen A, Pfundt R, Krumm N, Carvill GL, Li D, Amaral D, Brown N, Lockhart PJ, Scheffer IE, Alberti A, Shaw M, Pettinato R, Tervo R, de Leeuw N, Reijnders MR, Torchia BS, Peeters H, Thompson E, O'Roak BJ, Fichera M, Hehir-Kwa JY, Shendure J, Mefford HC, Haan E, Gécz J, de Vries BB, Romano C, Eichler EE | title = Refining analyses of copy number variation identifies specific genes associated with developmental delay | journal = Nature Genetics | volume = 46 | issue = 10 | pages= 1063–71 | date = October 2014 | pmid=25217958 | doi = 10.1038/ng.3092| pmc = 4177294 }}

SETBP1 is an oncogene; specific somatic mutations of this gene were discovered in patients affected by atypical Chronic Myeloid Leukemia (aCML) and related diseases. These mutations, which are identical to the ones present in SGS as germ line mutations, impair the degradation of SETBP1 and therefore cause increased cellular levels of the protein.{{cite journal | vauthors = Piazza R, Valletta S, Winkelmann N, Redaelli S, Spinelli R, Pirola A, Antolini L, Mologni L, Donadoni C, Papaemmanuil E, Schnittger S, Kim DW, Boultwood J, Rossi F, Gaipa G, De Martini GP, di Celle PF, Jang HG, Fantin V, Bignell GR, Magistroni V, Haferlach T, Pogliani EM, Campbell PJ, Chase AJ, Tapper WJ, Cross NC, Gambacorti-Passerini C | title = Recurrent SETBP1 mutations in atypical chronic myeloid leukemia | journal = Nature Genetics | volume = 45 | issue = 1 | date = Jan 2013 | pmid = 23222956 | doi = 10.1038/ng.2495 | pages=18–24 | pmc=3588142}}

{{reflist}}

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• {{cite journal | vauthors = Suphapeetiporn K, Srichomthong C, Shotelersuk V | title = SETBP1 mutations in two Thai patients with Schinzel-Giedion syndrome | journal = Clinical Genetics | volume = 79 | issue = 4 | date = Apr 2011 | pmid = 21371013 | doi = 10.1111/j.1399-0004.2010.01552.x | pages=391–3| s2cid = 29575566 }}
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• {{cite journal | vauthors = Filges I, Shimojima K, Okamoto N, Röthlisberger B, Weber P, Huber AR, Nishizawa T, Datta AN, Miny P, Yamamoto T | title = Reduced expression by SETBP1 haploinsufficiency causes developmental and expressive language delay indicating a phenotype distinct from Schinzel-Giedion syndrome | journal = Journal of Medical Genetics | volume = 48 | issue = 2 | date = Feb 2011 | pmid = 21037274 | doi = 10.1136/jmg.2010.084582 | pages=117–22| s2cid = 38823269 }}
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• {{cite journal | vauthors = Ishikawa K, Nagase T, Nakajima D, Seki N, Ohira M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro | journal = DNA Research | volume = 4 | issue = 5 | date = Oct 1997 | pmid = 9455477 | doi=10.1093/dnares/4.5.307 | pages=307–13| doi-access = free }}
• {{cite journal | vauthors = Piazza R, Valletta S, Winkelmann N, Redaelli S, Spinelli R, Pirola A, Antolini L, Mologni L, Donadoni C, Papaemmanuil E, Schnittger S, Kim DW, Boultwood J, Rossi F, Gaipa G, De Martini GP, di Celle PF, Jang HG, Fantin V, Bignell GR, Magistroni V, Haferlach T, Pogliani EM, Campbell PJ, Chase AJ, Tapper WJ, Cross NC, Gambacorti-Passerini C | title = Recurrent SETBP1 mutations in atypical chronic myeloid leukemia | journal = Nature Genetics | volume = 45 | issue = 1 | date = Jan 2013 | pmid = 23222956 | doi = 10.1038/ng.2495 | pages=18–24 | pmc=3588142}}
• {{cite journal | vauthors = Ganesan AK, Kho Y, Kim SC, Chen Y, Zhao Y, White MA | title = Broad spectrum identification of SUMO substrates in melanoma cells | journal = Proteomics | volume = 7 | issue = 13 | date = Jun 2007 | pmid = 17549794 | doi = 10.1002/pmic.200600971 | pages=2216–21| s2cid = 46295254 }}

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• [http://www.omim.org/entry/269150?search=number%3A%28269150%20OR%20611060%29&highlight=611060%20269150 OMIM entry on Schinzel-Giedion Midface Retraction Syndrome]

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• [http://www.setbp1.org SETBP1 Society - Non-profit providing support to individuals with SETBP1 disorder and their families, to promote discussion and fund research, and to bring awareness and education to the public.]

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