ArticlePloS one2014
A novel familial mutation in the PCSK1 gene that alters the oxyanion hole residue of proprotein convertase 1/3 and impairs its enzymatic activity.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Pathogenic Deep Intronic PCSK1 Variant Causes Proprotein Convertase 1/3 Deficiency in a Family.Clinical genetics · 2025Article
- Optimization of protocols for immunohistochemical assessment of enteric nervous system in formalin fixed human tissue.bioRxiv : the preprint server for biology · 2024Article
- New insights into the hypothalamic-pituitary-thyroid axis: a transcriptome- and proteome-wide association study.European thyroid journal · 2024Article
- The genetics of monogenic intestinal epithelial disorders.Human genetics · 2023Review
- Rare HeterozygousGenes · 2022Review
- Direct visualization of glucagon-like peptide-1 secretion by fluorescent fusion proteins.Journal of diabetes investigation · 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
- Novel Homozygous Inactivating Mutation in theGenes · 2021Article
- Long-Term Follow-up of a Case with Proprotein Convertase 1/3 Deficiency: Transient Diabetes Mellitus with Intervening Diabetic Ketoacidosis During Growth Hormone Therapy.Journal of clinical research in pediatric endocrinology · 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
- PCSK1 Variants and Human Obesity.Progress in molecular biology and translational science · 2016Review
- Revisiting PC1/3 Mutants: Dominant-Negative Effect of Endoplasmic Reticulum-Retained Mutants.Endocrinology · 2015Article
- Enteroendocrine Dysfunction in Two Saudi Sisters.Case reports in gastroenterologyArticle
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Four siblings presented with congenital diarrhea and various endocrinopathies. Exome sequencing and homozygosity mapping identified five regions, comprising 337 protein-coding genes that were shared by three affected siblings. Exome sequencing identified a novel homozygous N309K mutation in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene, encoding the neuroendocrine convertase 1 precursor (PC1/3) which was recently reported as a cause of Congenital Diarrhea Disorder (CDD). The PCSK1 mutation affected the oxyanion hole transition state-stabilizing amino acid within the active site, which is critical for appropriate proprotein maturation and enzyme activity. Unexpectedly, the N309K mutant protein exhibited normal, though slowed, prodomain removal and was secreted from both HEK293 and Neuro2A cells. However, the secreted enzyme showed no catalytic activity, and was not processed into the 66 kDa form. We conclude that the N309K enzyme is able to cleave its own propeptide but is catalytically inert against in trans substrates, and that this variant accounts for the enteric and systemic endocrinopathies seen in this large consanguineous kindred.
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