Gene: SMN1

Alternate names for this Gene: BCD541|GEMIN1|SMA|SMA1|SMA2|SMA3|SMA4|SMA@|SMN|SMNT|T-BCD541|TDRD16A

Gene Summary: This 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 and centromeric copies of this gene are nearly identical and encode the same protein. However, mutations in this gene, the telomeric copy, are associated with spinal muscular atrophy; mutations in the centromeric copy do not lead to disease. The centromeric copy may be a modifier of disease caused by mutation in the telomeric copy. The critical sequence difference between the two genes is a single nucleotide in exon 7, which is thought to be an exon splice enhancer. 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. The protein encoded by this gene localizes to both the cytoplasm and the nucleus. Within the nucleus, the protein localizes to subnuclear bodies called gems which are found near coiled bodies containing high concentrations of small ribonucleoproteins (snRNPs). This protein forms heteromeric complexes with proteins such as SIP1 and GEMIN4, and also interacts with several proteins known to be involved in the biogenesis of snRNPs, such as hnRNP U protein and the small nucleolar RNA binding protein. Multiple transcript variants encoding distinct isoforms have been described.

Gene is located in Chromosome: 5

Location in Chromosome : 5q13.2

Description of this Gene: survival of motor neuron 1, telomeric

Type of Gene: protein-coding

Gene: SMN2

Alternate names for this Gene: BCD541|C-BCD541|GEMIN1|SMNC|TDRD16B

Gene Summary: This 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 and centromeric copies of this gene are nearly identical and encode the same protein. 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. The critical sequence difference between the two genes is a single nucleotide in exon 7, which is thought to be an exon splice enhancer. 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. The full length protein encoded by this gene localizes to both the cytoplasm and the nucleus. Within the nucleus, the protein localizes to subnuclear bodies called gems which are found near coiled bodies containing high concentrations of small ribonucleoproteins (snRNPs). This protein forms heteromeric complexes with proteins such as SIP1 and GEMIN4, and also interacts with several proteins known to be involved in the biogenesis of snRNPs, such as hnRNP U protein and the small nucleolar RNA binding protein. Four transcript variants encoding distinct isoforms have been described.

Gene is located in Chromosome: 5

Location in Chromosome : 5q13.2

Description of this Gene: survival of motor neuron 2, centromeric

Type of Gene: protein-coding

rs1561498701 in SMN1;SMN2 gene and Absent reflex PMID 24498607 2013 A homozygous double mutation in SMN1: a complicated genetic diagnosis of SMA.

rs1554066397 in SMN1;SMN2 gene and Atrophic PMID 9837824 1998 Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number.

rs1561498701 in SMN1;SMN2 gene and Fasciculation, Tongue PMID 24498607 2013 A homozygous double mutation in SMN1: a complicated genetic diagnosis of SMA.

rs1561498701 in SMN1;SMN2 gene and Generalized hypotonia PMID 24498607 2013 A homozygous double mutation in SMN1: a complicated genetic diagnosis of SMA.

PMID 17761649 2007 Spinal muscular atrophy diagnostics.

rs104893922 in SMN1;SMN2 gene and HMN (Hereditary Motor Neuropathy) Proximal Type I PMID 10732817 1997 Molecular diagnosis of non-deletion SMA patients using quantitative PCR of SMN exon 7.

PMID 15580564 2005 Molecular and functional analysis of intragenic SMN1 mutations in patients with spinal muscular atrophy.

PMID 14715275 2004 Rpp20 interacts with SMN and is re-distributed into SMN granules in response to stress.

PMID 21088113 2011 HuD interacts with survival motor neuron protein and can rescue spinal muscular atrophy-like neuronal defects.

PMID 15249625 2004 Detection of novel mutations in the SMN Tudor domain in type I SMA patients.

PMID 7813012 1995 Identification and characterization of a spinal muscular atrophy-determining gene.

PMID 21389246 2011 The survival of motor neuron (SMN) protein interacts with the mRNA-binding protein HuD and regulates localization of poly(A) mRNA in primary motor neuron axons.

PMID 9147655 1997 Missense mutation clustering in the survival motor neuron gene: a role for a conserved tyrosine and glycine rich region of the protein in RNA metabolism?

PMID 17761659 2007 Consensus statement for standard of care in spinal muscular atrophy.

PMID 22510849 2012 Clinical utility gene card for: proximal spinal muscular atrophy.

PMID 27939059 2016 Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study.

PMID 8922999 1996 An 11 base pair duplication in exon 6 of the SMN gene produces a type I spinal muscular atrophy (SMA) phenotype: further evidence for SMN as the primary SMA-determining gene.

rs104893932 in SMN1;SMN2 gene and Juvenile Spinal Muscular Atrophy PMID 14715275 2004 Rpp20 interacts with SMN and is re-distributed into SMN granules in response to stress.

PMID 9158159 1997 Missense mutations in exon 6 of the survival motor neuron gene in patients with spinal muscular atrophy (SMA).

PMID 10732817 1997 Molecular diagnosis of non-deletion SMA patients using quantitative PCR of SMN exon 7.

PMID 17761659 2007 Consensus statement for standard of care in spinal muscular atrophy.

PMID 9837824 1998 Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number.

rs1561498701 in SMN1;SMN2 gene and Muscular Atrophy, Spinal, Type II PMID 24498607 2013 A homozygous double mutation in SMN1: a complicated genetic diagnosis of SMA.

PMID 14715275 2004 Rpp20 interacts with SMN and is re-distributed into SMN granules in response to stress.

PMID 21088113 2011 HuD interacts with survival motor neuron protein and can rescue spinal muscular atrophy-like neuronal defects.

PMID 9837824 1998 Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number.

PMID 10732802 1998 Identification of a novel missense mutation of the SMN(T) gene in two siblings with spinal muscular atrophy.

PMID 9158159 1997 Missense mutations in exon 6 of the survival motor neuron gene in patients with spinal muscular atrophy (SMA).

rs1554066397 in SMN1;SMN2 gene and Proximal muscle weakness PMID 9837824 1998 Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number.

rs772466166 in SMN1;SMN2 gene and Proximal weakness PMID 21542063 2011 A leaky splicing mutation affecting SMN1 exon 7 inclusion explains an unexpected mild case of spinal muscular atrophy.

rs1561500885 in SMN1;SMN2 gene and Respiratory Failure PMID 17761649 2007 Spinal muscular atrophy diagnostics.

rs772466166 in SMN1;SMN2 gene and SPINAL MUSCULAR ATROPHY, TYPE IV PMID 21542063 2011 A leaky splicing mutation affecting SMN1 exon 7 inclusion explains an unexpected mild case of spinal muscular atrophy.

rs1561498701 in SMN1;SMN2 gene and Severe muscular hypotonia PMID 24498607 2013 A homozygous double mutation in SMN1: a complicated genetic diagnosis of SMA.