Biology:SETBP1

Generic protein structure example

SET binding protein 1 is a protein that in humans is encoded by the SETBP1 gene.

Gene

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.

Function

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. There is still more to learn about the overall function of the SETBP1 protein and the effect of SET binding.

Clinical significance

Gain-of-function mutations in the SETBP1 gene are associated with Schinzel–Giedion syndrome.

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.

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.

Further reading

• "Identification and characterization of SEB, a novel protein that binds to the acute undifferentiated leukemia-associated protein SET". European Journal of Biochemistry / FEBS 268 (5): 1340–51. Mar 2001. doi:10.1046/j.1432-1327.2001.02000.x. PMID 11231286. 
• "SETBP1 mutations in two Thai patients with Schinzel-Giedion syndrome". Clinical Genetics 79 (4): 391–3. Apr 2011. doi:10.1111/j.1399-0004.2010.01552.x. PMID 21371013. 
• "Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1". Nature Medicine 12 (4): 401–9. Apr 2006. doi:10.1038/nm1393. PMID 16582916. 
• "Reduced expression by SETBP1 haploinsufficiency causes developmental and expressive language delay indicating a phenotype distinct from Schinzel-Giedion syndrome". Journal of Medical Genetics 48 (2): 117–22. Feb 2011. doi:10.1136/jmg.2010.084582. PMID 21037274. 
• "372 kb microdeletion in 18q12.3 causing SETBP1 haploinsufficiency associated with mild mental retardation and expressive speech impairment". European Journal of Medical Genetics 55 (3): 216–21. Mar 2012. doi:10.1016/j.ejmg.2012.01.005. PMID 22333924. 
• "Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases". PLOS Genetics 8 (5): e1002746. May 2012. doi:10.1371/journal.pgen.1002746. PMID 22693459. 
• "Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro". DNA Research 4 (5): 307–13. Oct 1997. doi:10.1093/dnares/4.5.307. PMID 9455477. 
• "Recurrent SETBP1 mutations in atypical chronic myeloid leukemia". Nature Genetics 45 (1): 18–24. Jan 2013. doi:10.1038/ng.2495. PMID 23222956. 
• "Broad spectrum identification of SUMO substrates in melanoma cells". Proteomics 7 (13): 2216–21. Jun 2007. doi:10.1002/pmic.200600971. PMID 17549794. 

External links

• OMIM entry on Schinzel-Giedion Midface Retraction Syndrome

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

• 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.