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Published on: August 28, 2018
Genetic and functional characterization of PCSK1
Hélène Choquet1, Pieter Stijnen, John W M Creemers
1CNRS-8090-Institute of Biology, Pasteur Institute, Lille, France. hchoquet@gallo.ucsf.edu
Mutations in the PCSK1 gene, encoding proprotein convertase subtilisin/kexin type 1 (PC1/3), are linked to obesity. Further research may uncover more genetic variants contributing to obesity risk.
Area of Science:
- Biochemistry
- Genetics
- Neuroendocrinology
Background:
- Proprotein convertase subtilisin/kexin type 1 (PC1/3) is a neuroendocrine enzyme crucial for processing precursor proteins.
- PC1/3 is synthesized as a zymogen (proPC1/3) and undergoes autocatalytic cleavage in the endoplasmic reticulum.
- The mature PC1/3 protein is stored in secretory vesicles alongside its substrates.
Purpose of the Study:
- To investigate the role of PC1/3 in obesity.
- To examine the genetic basis of obesity related to PCSK1 gene variants.
Main Methods:
- Analysis of the PCSK1 gene and its encoded protein, PC1/3.
- Review of existing literature on PCSK1 mutations and obesity.
- Identification of monogenic and polygenic obesity links to PCSK1 variants.
Main Results:
- Compound-inactivating mutations in PCSK1 cause monogenic obesity.
- Common nonsynonymous PCSK1 variants contribute to polygenic obesity risk.
- Rare PCSK1 variants have been found in extremely obese individuals, requiring functional characterization.
Conclusions:
- The PCSK1 gene, encoding PC1/3, is a significant factor in obesity development.
- Both rare and common variants in PCSK1 are associated with obesity risk.
- Further sequencing in larger obese cohorts may identify additional risk-conferring variants.
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