Fibronectin Type III Domain-Containing Protein 5

Alternative Names

  • FNDC5
  • FRCP2
  • Irisin

Associated Diseases

Type 2 Diabetes Mellitus
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OMIM Number

611906

Gene Map Locus
1p35.1

Description

The FNDC5 gene encodes a protein that is secreted from muscle cells during exercise.  This protein is called Fibronectin type III domain-containing protein 5, and it is thought to play a role in fat development.  The protein is actually a prohormone that undergoes post-translational processing to produce a protein called Irisin.  Because of its release by muscle cells in response to muscular contraction, Irisin is classed as a myokine.  There is evidence to show that Irisin may be involved in the development of brown fat, weight loss, and protection against diabetes, at least in mice. 

It has been postulated that Irisin could be used for therapeutic intervention for metabolic disease and other disorders that are improved with exercise.  Mutations in this gene cause type 2 diabetes.

Molecular Genetics

The FNDC5 gene contains six exons and spans 8.47 kb.  The encoded protein has 212 amino acids with a molecular mass of 23 KDa.  FNDC5 is a membrane protein, and is made up of a short cytoplasmic hydrophobic domain that is anchored in the cell membrane, a transmembrane segment, and an ectodomain consisting of a ~100 kDa fibronectin type III (FNIII) domain.  Post translational processing involves the removal of the N-terminal signal peptide, proteolytic cleavage of the peptide from the C-terminal moiety, and glycosylation.  The remaining 112 residue Irisin is released as a peptide hormone.  

Epidemiology in the Arab World

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Other Reports

Saudi Arabia

Al-Daghri et al., (2016) randomly selected 814 Saudi adults, 394 of whom had type 2 diabetes, from a biomarker screening project in Riyadh.  The aim was to examine the possible role of the following five FNDC5 polymorphisms; rs3480A/G, rs1746661G/T, rs1298190A/G, rs726344A/G and rs1570569G/T in type 2 diabetes and obesity since both were common in Saudi Arabia.  DNA samples from all subjects were genotyped for the five SNPs using TaqMan genotyping assay.  Authors found that serum Irisin levels were higher in patients with type 2 diabetes compared to controls.  The analyses of the 5 SNPs showed that rs3480 GG associated with decreased risk of obesity and low body mass index.  The rs1746661 G allele was associated with high levels of triglyceride.  The rs157069 TT genotype was associated with high levels of fasting insulin and HOMA-IR, while it was associated with lower levels of circulating Irisin.  Authors suggested that further analysis was needed to understand the underlying mechanisms.  

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