ArticleGut2014
Functional effects of 13 rare PRSS1 variants presumed to cause chronic pancreatitis.
Article in Gut, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Trypsinogen (PRSS1 and PRSS2) gene dosage correlates with pancreatitis risk across genetic and transgenic studies: a systematic review and re-analysis.Human genetics · 2022Pooled it
- Scale and Scope of Gene-Alcohol Interactions in Chronic Pancreatitis: A Systematic Review.Genes · 2021Pooled it
- Patient-derived organoids reveal ductal dysfunction and CFTR-modulator responses in chronic pancreatitis.Cell stem cell · 2026Article
- High-fat diet accelerates pancreas pathology in theFrontiers in physiology · 2026Article
- From single-pathway cascade to network pathophysiology: how genetically engineered mouse models reshaped our understanding of pancreatitis.Frontiers in physiology · 2026Review
- Chronic pancreatitis patient-derived organoids reveal new paths to precision therapeutics.bioRxiv : the preprint server for biology · 2025Article
- Chymotrypsin B2 (CTRB2) Deletion Variant Induces Endoplasmic Reticulum Stress but does not Increase Risk for Chronic Pancreatitis.Pancreas · 2025Article
- The 12-Year Experience of the Hungarian Pancreatic Study Group.Journal of clinical medicine · 2025Review
- Misfolding PRSS1 variant p.Ala61Val in a case of suspected intrauterine pancreatitis.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2025Article
- Case Report: a family report of hereditary pancreatitis caused by SPINK1 and PRSS1 gene mutations.Frontiers in genetics · 2025Article
- SEC16A Variants Predispose to Chronic Pancreatitis by Impairing ER-to-Golgi Transport and Inducing ER Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Clinical and Genetic Description of Hereditary Chronic Pancreatitis in Pakistani Children.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2023Article
- Endoplasmic stress-inducing variants in carboxyl ester lipase and pancreatic cancer risk.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2022Article
- Expanding ACMG variant classification guidelines into a general framework.Human genomics · 2022Article
- Misfolding-induced chronic pancreatitis in CPA1 N256K mutant mice is unaffected by global deletion of Ddit3/Chop.Scientific reports · 2022Article
- The CEL-HYB1 Hybrid Allele Promotes Digestive Enzyme Misfolding and Pancreatitis in Mice.Cellular and molecular gastroenterology and hepatology · 2022Article
- Review
- Silencing PRSS1 suppresses the growth and proliferation of gastric carcinoma cells via the ERK pathway.International journal of biological sciences · 2021Article
- Genetic Abnormalities in Pancreatitis: An Update on Diagnosis, Clinical Features, and Treatment.Diagnostics (Basel, Switzerland) · 2020Review
- ATF6 regulates the development of chronic pancreatitis by inducing p53-mediated apoptosis.Cell death & disease · 2019Article
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveHereditary pancreatitis is caused by mutations in human cationic trypsinogen (PRSS1) which lead to increased autoactivation by altering chymotrypsin C (CTRC)-dependent trypsinogen activation and degradation. Exceptions are some cysteine mutations which cause misfolding, intracellular retention and endoplasmic reticulum stress. Clinical relevance of many PRSS1 variants found in patients with sporadic chronic pancreatitis is unknown but often assumed by analogy with known disease-causing mutations. Functional comparison of PRSS1 variants found in sporadic and hereditary cases is needed to resolve this dilemma.
designHere, we investigated the functional phenotype of 13 published PRSS1 variants with respect to autoactivation in the presence of CTRC and cellular secretion.
resultsOnly mutation p.D100H increased trypsinogen autoactivation, but this gain in function was offset by a marked reduction in secretion. Five mutants (p.P36R, p.G83E, p.I88N, p.V123M, p.S124F) showed decreased autoactivation due to increased degradation by CTRC. Five mutants exhibited strongly (p.D100H, p.C139F) or moderately (p.K92N, p.S124F, p.G208A) reduced secretion, whereas mutant p.K170E showed slightly increased secretion. Mutant p.I88N was also secreted to higher levels but was rapidly degraded by CTRC. Finally, three mutants (p.Q98K, p.T137M, p.S181G) had no phenotypic alterations relative to wild-type trypsinogen.
conclusionsRare PRSS1 variants found in sporadic chronic pancreatitis do not stimulate autoactivation but may cause increased degradation, impaired secretion or no functional change. Variants with reduced secretion are likely pathogenic due to mutation-induced misfolding and consequent endoplasmic reticulum stress.
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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.