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SMN2
survival of motor neuron 2, centromeric
The SMN2 gene provides instructions for making the survival motor neuron (SMN) protein, which is vital for the proper function and maintenance of motor neurons throughout the body. The SMN2 gene is responsible for producing the SMN protein, which plays a critical role in the maintenance of motor neurons.
SMN2 is located on the long (q) arm of chromosome 5, at band 5q13.2. Arm ratio per GRCh38 - banding schematic.
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The SMN2 gene, also known as survival of motor neuron 2, centromeric, is crucial for producing the survival motor neuron (SMN) protein. This protein is widely distributed throughout the body, with its highest concentrations found in the spinal cord. The SMN protein is a key component of the SMN complex, which is essential for maintaining specialised nerve cells called motor neurons.
Motor neurons, located in the spinal cord and brainstem, are responsible for transmitting signals from the brain and spinal cord to skeletal muscles. These signals initiate muscle contraction, enabling body movement. Variations in the SMN2 gene, particularly the number of copies, can influence the amount of functional SMN protein produced and modify the severity of certain inherited conditions.
What the gene does
The SMN2 gene encodes the survival motor neuron (SMN) protein. This protein is a central part of the SMN complex, which has several important functions within cells. One primary role of the SMN complex is in processing messenger RNA (mRNA) molecules. mRNA acts as a genetic blueprint for creating proteins, and the complex assists in assembling the cellular machinery required to process premature mRNA into its mature, functional form.
While the SMN2 gene produces the SMN protein, only a specific isoform (isoform d) is full-sized and fully functional. Other isoforms produced by SMN2 are typically smaller and are rapidly degraded. Although the full-sized protein from SMN2 is identical to that produced by the SMN1 gene, SMN2 usually contributes only about 10-15% of the total functional SMN protein in a cell. The SMN complex is also important for the development of nerve cell extensions, known as dendrites and axons, which are crucial for transmitting impulses between neurons and from neurons to muscles.
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Chromosome location
The SMN2 gene is located on chromosome 5 at position 5q13.2. Humans typically have two copies of the SMN1 gene and one to two copies of the SMN2 gene per cell, though the number of SMN2 copies can vary, with some individuals having up to eight copies.
Protein structure
The SMN2 protein consists of 294 amino acids. Its structure includes several distinct regions and domains. An N-terminal Disordered region spans amino acids 1-32, followed by a region from amino acids 26-51 that Interacts with GEMIN2. Another Disordered region is present from amino acids 59-88. A key feature is the Tudor domain, found between amino acids 91-151. A region from amino acids 97-209 is Required for interaction with RPP20/POP7, and a Disordered region extends from amino acids 156-222. Towards the C-terminus, a P2 region (amino acids 240-267) is a binding site for SNRPB. Amino acids 252-280 are Involved in homooligomerization, and the region from amino acids 279-294 is Required for interaction with SYNCRIP.
Key variants
Genetic variations within the SMN2 gene can affect the quantity and quality of the SMN protein produced. These variations, which include differences in copy number, can influence the overall cellular levels of functional SMN protein. The specific impact of a variant can depend on its location and type.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
While extra copies of the SMN2 gene do not directly cause spinal muscular atrophy, they are known to modify the condition's severity. Spinal muscular atrophy is characterised by the loss of motor neurons, leading to progressive muscle weakness and wasting (atrophy) in muscles used for movement. The more copies of the SMN2 gene an individual possesses, the more functional SMN protein they produce, which can result in a milder presentation of spinal muscular atrophy.
No disease links recorded for this gene in our reference set.
UK clinical status
Frequently asked questions
What is the primary function of the SMN2 gene?
The SMN2 gene primarily provides instructions for making the survival motor neuron (SMN) protein. This protein is essential for the maintenance and proper functioning of motor neurons, which transmit signals for muscle movement.
How does the SMN2 gene differ from the SMN1 gene?
Both SMN1 and SMN2 genes produce the SMN protein. However, SMN2 typically produces only a small percentage (10-15%) of full-sized, functional SMN protein, while SMN1 is the primary source. SMN2 often yields smaller, less stable isoforms.
Can the number of SMN2 gene copies vary?
Yes, the number of SMN2 gene copies can vary significantly among individuals, ranging from one to eight copies. A higher number of SMN2 copies generally correlates with increased production of functional SMN protein.
References
- Fuller HR, Gillingwater TH, Wishart TM. Commonality amid diversity: Multi-study proteomic identification of conserved disease mechanisms in spinal muscular atrophy. Neuromuscular disorders : NMD. 2016. PMID: 27460344
- Farrar MA, Kiernan MC. The Genetics of Spinal Muscular Atrophy: Progress and Challenges. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2015. PMID: 25413156
- Kolb SJ, Kissel JT. Spinal Muscular Atrophy. Neurologic clinics. 2015. PMID: 26515624
- Prior TW, Krainer AR, Hua Y. A positive modifier of spinal muscular atrophy in the SMN2 gene. American journal of human genetics. 2009. PMID: 19716110
- Kolb SJ, Battle DJ, Dreyfuss G. Molecular functions of the SMN complex. Journal of child neurology. 2007. PMID: 17761654
- Cartegni L, Hastings ML, Calarco JA. Determinants of exon 7 splicing in the spinal muscular atrophy genes, SMN1 and SMN2. American journal of human genetics. 2006. PMID: 16385450
- Wirth B, Brichta L, Schrank B. Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number. Human genetics. 2006. PMID: 16508748
- Gubitz AK, Feng W, Dreyfuss G. The SMN complex. Experimental cell research. 2004. PMID: 15120993
- Prior TW, Swoboda KJ, Scott HD. Homozygous SMN1 deletions in unaffected family members and modification of the phenotype by SMN2. American journal of medical genetics. Part A. 2004. PMID: 15378550