SMG9 Nonsense-Mediated mRNA Decay Factor

Alternative Names

  • SMG9
  • Chromosome 19 Open Reading Frame 61
  • C19ORF61
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OMIM Number

613176

Gene Map Locus
19q13.31

Description

SMG9 (SMG9 Nonsense Mediated MRNA Decay Factor) is a protein coding gene that is involved in several pathways such as gene expression and viral mRNA translation.  SMG9 serves as a component of the Nonsense Mediated Decay (NMD) process, which is a transcriptional regulatory mechanism that degrades transcripts with premature stop codons.  The SMG9 protein has been shown to interact with other components of the NMD machinery to form the SURF complex.  This complex is integral for the activation of the protein UPF1, which in turn halts translation at premature stop codons. 

Mutations in most genes involved in NMD are associated with embryonic lethality or major malformation syndromes.  Mutations in SMG9 have been shown to cause Heart and Brain Malformation Syndrome. 

Molecular Genetics

SMG9 gene is located on the long arm of chromosome 19, where it spans a length of about 27 kb.  The encoded protein is composed of 520 amino acids and has a molecular mass of 57 kDa.  The protein can self-associate to form homodimers and can also form heterodimers with SMG8, another NMD component.  Four pathogenic variants in the SMG9 gene have been reported in the ClinVar database. 

Epidemiology in the Arab World

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Other Reports

Saudi Arabia

Shaheen et al., (2016) enrolled two Saudi families in which affected patients shared a similar pattern of malformations.  Both patients were born to consanguineous parents and family histories were positive for similar presentations.  Linkage analysis and exome sequencing revealed p.Pro174Argfs*12 and p.Tyr197Aspfs*10 mutations in the SMG9 gene.  Analysis of patient cells showed dysregulation of the transcriptional profile compared to controls.  However, there was no much impairment of nonsense-mediated mRNA decay.  The authors concluded that mutations in the SMG9 gene caused a distinctive congenital anomaly and that more studies were needed to further delineate associated phenotypes.

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