ArticlePloS one2013
Functional consequences of a novel variant of PCSK1.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.
- Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals.Human molecular genetics · 2015Pooled it
- Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus.PLoS genetics · 2015Pooled it
- A patient with ROHHAD syndrome and leptin-melanocortin pathway gene variations. Correlation or just a coincidence? Case report.Hormones (Athens, Greece) · 2026Review
- Cardiometabolic Risk Markers in Children With Obesity and Variants inJournal of the Endocrine Society · 2024Article
- Association ofGenes · 2023Article
- Detection of lineage-reprogramming efficiency of tumor cells in a 3D-printed liver-on-a-chip model.Theranostics · 2023Article
- Testing for rare genetic causes of obesity: findings and experiences from a pediatric weight management program.International journal of obesity (2005) · 2022Article
- The G209R mutant mouse as a model for human PCSK1 polyendocrinopathy.Endocrinology · 2022Article
- Modulation of PC1/3 activity by a rare double-site homozygous mutation.Frontiers in pediatrics · 2022Article
- Gene expression atlas of energy balance brain regions.JCI insight · 2021Article
- Molecular evolution of PCSK family: Analysis of natural selection rate and gene loss.PloS one · 2021Article
- Functional and clinical relevance of novel and knownMolecular metabolism · 2017Article
- Endoplasmic reticulum-associated degradation of the mouse PC1/3-N222D hypomorph and human PCSK1 mutations contributes to obesity.International journal of obesity (2005) · 2016Article
- Revisiting PC1/3 Mutants: Dominant-Negative Effect of Endoplasmic Reticulum-Retained Mutants.Endocrinology · 2015Article
- Mechanism of Fine-tuning pH Sensors in Proprotein Convertases: IDENTIFICATION OF A pH-SENSING HISTIDINE PAIR IN THE PROPEPTIDE OF PROPROTEIN CONVERTASE 1/3.The Journal of biological chemistry · 2015Article
- Biochemical and cell biological properties of the human prohormone convertase 1/3 Ser357Gly mutation: a PC1/3 hypermorph.Endocrinology · 2014Article
- Defective transport of the obesity mutant PC1/3 N222D contributes to loss of function.Endocrinology · 2014Article
- Article
- Genetics of the first seven proprotein convertase enzymes in health and disease.Current genomics · 2013Article
- Proprotein convertases in high-density lipoprotein metabolism.Biomarker research · 2013Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCommon single nucleotide polymorphisms (SNPs) in proprotein convertase subtilisin/kexin type 1 with modest effects on PC1/3 in vitro have been associated with obesity in five genome-wide association studies and with diabetes in one genome-wide association study. We here present a novel SNP and compare its biosynthesis, secretion and catalytic activity to wild-type enzyme and to SNPs that have been linked to obesity. METHODOLOGY/PRINCIPAL
findingsA novel PC1/3 variant introducing an Arg to Gln amino acid substitution at residue 80 (within the secondary cleavage site of the prodomain) (rs1799904) was studied. This novel variant was selected for analysis from the 1000 Genomes sequencing project based on its predicted deleterious effect on enzyme function and its comparatively more frequent allele frequency. The actual existence of the R80Q (rs1799904) variant was verified by Sanger sequencing. The effects of this novel variant on the biosynthesis, secretion, and catalytic activity were determined; the previously-described obesity risk SNPs N221D (rs6232), Q665E/S690T (rs6234/rs6235), and the Q665E and S690T SNPs (analyzed separately) were included for comparative purposes. The novel R80Q (rs1799904) variant described in this study resulted in significantly detrimental effects on both the maturation and in vitro catalytic activity of PC1/3. CONCLUSION/SIGNIFICANCE: Our findings that this novel R80Q (rs1799904) variant both exhibits adverse effects on PC1/3 activity and is prevalent in the population suggests that further biochemical and genetic analysis to assess its contribution to the risk of metabolic disease within the general population is warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.