Survival of motor neuron 2 (''SMN2'') is a
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
that encodes the
SMN protein (full and truncated) in humans.
Gene
The ''SMN2'' gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and
repetitive element
Repeated sequences (also known as repetitive elements, repeating units or repeats) are short or long patterns of nucleic acids (DNA or RNA) that occur in multiple copies throughout the genome
In the fields of molecular biology and geneti ...
s 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
A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...
(''
SMN1
Survival of motor neuron 1 (''SMN1''), also known as component of gems 1 or ''GEMIN1'', is a gene that encodes the SMN protein in humans.
Gene
''SMN1'' is the telomeric copy of the gene encoding the SMN protein; the centromeric copy is terme ...
'') and
centromeric
The centromere links a pair of sister chromatids together during cell division. This constricted region of chromosome connects the sister chromatids, creating a short arm (p) and a long arm (q) on the chromatids. During mitosis, spindle fibers ...
(''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
In molecular biology, an exonic splicing enhancer (ESE) is a DNA sequence motif consisting of 6 bases within an exon that directs, or enhances, accurate splicing of heterogeneous nuclear RNA ( hnRNA) or pre-mRNA into messenger RNA (mRNA). Introd ...
. 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).
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.
Clinical significance
While mutations in the telomeric copy are associated with
spinal muscular atrophy
Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting. It is usually diagnosed in infancy or early childhood and if left untreated it is the most common genetic ...
, 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.
References
Further reading
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{{NLM content
Spinal muscular atrophy