SMN2

The SMN2 gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. The telomeric (SMN1) and centromeric (SMN2) copies of this gene are nearly identical and encode the same protein. The critical sequence difference between the two genes is a single nucleotide in exon 7, which is thought to be an exon splice enhancer. The nucleotide substitution in SMN2 results in around 80-90% of its transcripts to be a truncated, unstable protein of no biological function (Δ7SMN) and only 10-20% of its transcripts being full-length protein (fl-SMN).{{citation needed|date=August 2021}}

Note that the nine exons of both the telomeric and centromeric copies are designated historically as exon 1, 2a, 2b, and 3–8. It is thought that gene conversion events may involve the two genes, leading to varying copy numbers of each gene.

While mutations in the telomeric copy are associated with spinal muscular atrophy, mutations in this gene, the centromeric copy, do not lead to disease. This gene may be a modifier of disease caused by mutation in the telomeric copy.{{citation needed|date=August 2021}}

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• {{cite journal | vauthors = Watihayati MS, Fatemeh H, Marini M, Atif AB, Zahiruddin WM, Sasongko TH, Tang TH, Zabidi-Hussin ZA, Nishio H, Zilfalil BA | title = Combination of SMN2 copy number and NAIP deletion predicts disease severity in spinal muscular atrophy | journal = Brain & Development | volume = 31 | issue = 1 | pages = 42–5 | date = January 2009 | pmid = 18842367 | doi = 10.1016/j.braindev.2008.08.012 | s2cid = 206312220 }}
• {{cite journal | vauthors = Prior TW, Krainer AR, Hua Y, Swoboda KJ, Snyder PC, Bridgeman SJ, Burghes AH, Kissel JT | title = A positive modifier of spinal muscular atrophy in the SMN2 gene | journal = American Journal of Human Genetics | volume = 85 | issue = 3 | pages = 408–13 | date = September 2009 | pmid = 19716110 | pmc = 2771537 | doi = 10.1016/j.ajhg.2009.08.002 }}
• {{cite journal | vauthors = Coady TH, Baughan TD, Shababi M, Passini MA, Lorson CL | title = Development of a single vector system that enhances trans-splicing of SMN2 transcripts | journal = PLOS ONE | volume = 3 | issue = 10 | pages = e3468 | year = 2008 | pmid = 18941511 | pmc = 2565107 | doi = 10.1371/journal.pone.0003468 | bibcode = 2008PLoSO...3.3468C | editor1-last = Valcarcel | editor1-first = Juan | doi-access = free }}
• {{cite journal | vauthors = Elsheikh B, Prior T, Zhang X, Miller R, Kolb SJ, Moore D, Bradley W, Barohn R, Bryan W, Gelinas D, Iannaccone S, Leshner R, Mendell JR, Mendoza M, Russman B, Smith S, King W, Kissel JT | title = An analysis of disease severity based on SMN2 copy number in adults with spinal muscular atrophy | journal = Muscle & Nerve | volume = 40 | issue = 4 | pages = 652–6 | date = October 2009 | pmid = 19760790 | doi = 10.1002/mus.21350 | s2cid = 44901599 }}
• {{cite journal | vauthors = Workman E, Saieva L, Carrel TL, Crawford TO, Liu D, Lutz C, Beattie CE, Pellizzoni L, Burghes AH | title = A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice | journal = Human Molecular Genetics | volume = 18 | issue = 12 | pages = 2215–29 | date = June 2009 | pmid = 19329542 | pmc = 2685758 | doi = 10.1093/hmg/ddp157 }}
• {{cite journal | vauthors = Bose JK, Wang IF, Hung L, Tarn WY, Shen CK | title = TDP-43 overexpression enhances exon 7 inclusion during the survival of motor neuron pre-mRNA splicing | journal = The Journal of Biological Chemistry | volume = 283 | issue = 43 | pages = 28852–9 | date = October 2008 | pmid = 18703504 | pmc = 2661999 | doi = 10.1074/jbc.M805376200 | doi-access = free }}
• {{cite journal | vauthors = Hauke J, Riessland M, Lunke S, Eyüpoglu IY, Blümcke I, El-Osta A, Wirth B, Hahnen E | title = Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition | journal = Human Molecular Genetics | volume = 18 | issue = 2 | pages = 304–17 | date = January 2009 | pmid = 18971205 | pmc = 2638778 | doi = 10.1093/hmg/ddn357 }}
• {{cite journal | vauthors = Corcia P, Camu W, Praline J, Gordon PH, Vourch P, Andres C | title = The importance of the SMN genes in the genetics of sporadic ALS | journal = Amyotrophic Lateral Sclerosis | volume = 10 | issue = 5–6 | pages = 436–40 | year = 2009 | pmid = 19922137 | doi = 10.3109/17482960902759162 | s2cid = 2326464 }}
• {{cite journal | vauthors = Tiziano FD, Pinto AM, Fiori S, Lomastro R, Messina S, Bruno C, Pini A, Pane M, D'Amico A, Ghezzo A, Bertini E, Mercuri E, Neri G, Brahe C | title = SMN transcript levels in leukocytes of SMA patients determined by absolute real-time PCR | journal = European Journal of Human Genetics | volume = 18 | issue = 1 | pages = 52–8 | date = January 2010 | pmid = 19603064 | pmc = 2987170 | doi = 10.1038/ejhg.2009.116 }}
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• {{cite journal | vauthors = Arkblad E, Tulinius M, Kroksmark AK, Henricsson M, Darin N | title = A population-based study of genotypic and phenotypic variability in children with spinal muscular atrophy | journal = Acta Paediatrica | volume = 98 | issue = 5 | pages = 865–72 | date = May 2009 | pmid = 19154529 | doi = 10.1111/j.1651-2227.2008.01201.x | s2cid = 3134264 }}
• {{cite journal | vauthors = Paushkin S, Gubitz AK, Massenet S, Dreyfuss G | title = The SMN complex, an assemblyosome of ribonucleoproteins | journal = Current Opinion in Cell Biology | volume = 14 | issue = 3 | pages = 305–12 | date = June 2002 | pmid = 12067652 | doi = 10.1016/S0955-0674(02)00332-0 }}
• {{cite journal | vauthors = Farooq F, Balabanian S, Liu X, Holcik M, MacKenzie A | title = p38 Mitogen-activated protein kinase stabilizes SMN mRNA through RNA binding protein HuR | journal = Human Molecular Genetics | volume = 18 | issue = 21 | pages = 4035–45 | date = November 2009 | pmid = 19648294 | doi = 10.1093/hmg/ddp352 | doi-access = free }}
• {{cite journal | vauthors = Hasanzad M, Golkar Z, Kariminejad R, Hadavi V, Almadani N, Afroozan F, Salahshurifar I, Shafeghati Y, Kahrizi K, Najmabadi H | title = Deletions in the survival motor neuron gene in Iranian patients with spinal muscular atrophy | journal = Annals of the Academy of Medicine, Singapore | volume = 38 | issue = 2 | pages = 139–41 | date = February 2009 | doi = 10.47102/annals-acadmedsg.V38N2p139 | pmid = 19271042 }}
• {{cite journal | vauthors = Martins de Araújo M, Bonnal S, Hastings ML, Krainer AR, Valcárcel J | title = Differential 3' splice site recognition of SMN1 and SMN2 transcripts by U2AF and U2 snRNP | journal = RNA | volume = 15 | issue = 4 | pages = 515–23 | date = April 2009 | pmid = 19244360 | pmc = 2661831 | doi = 10.1261/rna.1273209 }}
• {{cite journal | vauthors = Song F, Qu YJ, Zou LP, Wang LW, Long MJ, Wang X, Yang YL, Chen Q, Wang H, Jin YW | title = [Molecular analysis of survival motor neuron gene in 338 suspicious children patients with spinal muscular atrophy] | journal = Zhonghua Er Ke Za Zhi = Chinese Journal of Pediatrics | volume = 46 | issue = 12 | pages = 919–23 | date = December 2008 | pmid = 19134255 }}
• {{cite journal | vauthors = Irimura S, Kitamura K, Kato N, Saiki K, Takeuchi A, Matsuo M, Nishio H, Lee MJ | title = HnRNP C1/C2 may regulate exon 7 splicing in the spinal muscular atrophy gene SMN1 | journal = The Kobe Journal of Medical Sciences | volume = 54 | issue = 5 | pages = E227-36 | year = 2009 | pmid = 19628962 }}
• {{cite journal | vauthors = Yong J, Wan L, Dreyfuss G | title = Why do cells need an assembly machine for RNA-protein complexes? | journal = Trends in Cell Biology | volume = 14 | issue = 5 | pages = 226–32 | date = May 2004 | pmid = 15130578 | doi = 10.1016/j.tcb.2004.03.010 }}
• {{cite journal | vauthors = Chen HH, Chang JG, Lu RM, Peng TY, Tarn WY | title = The RNA binding protein hnRNP Q modulates the utilization of exon 7 in the survival motor neuron 2 (SMN2) gene | journal = Molecular and Cellular Biology | volume = 28 | issue = 22 | pages = 6929–38 | date = November 2008 | pmid = 18794368 | pmc = 2573304 | doi = 10.1128/MCB.01332-08 }}
• {{cite journal | vauthors = Cogulu O, Durmaz B, Pehlivan S, Alpman A, Ozkinay F | title = Evaluation of the SMN and NAIP genes in a family: homozygous deletion of the SMN2 gene in the fetus and outcome of the pregnancy | journal = Genetic Testing and Molecular Biomarkers | volume = 13 | issue = 3 | pages = 287–8 | date = June 2009 | pmid = 19397406 | doi = 10.1089/gtmb.2008.0139 }}

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Category:Spinal muscular atrophy