PRSS1

Chr 7

serine protease 1

Also known as: TRP1, TRY1, TRY4, TRYP1

NCBI Gene: 5644ENSG00000204983UniProt: P07477

This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is secreted by the pancreas and cleaved to its active form in the small intestine. It is active on peptide linkages involving the carboxyl group of lysine or arginine. Mutations in this gene are associated with hereditary pancreatitis. This gene and several other trypsinogen genes are localized to the T cell receptor beta locus on chromosome 7. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtPancreatitis, hereditary
287
ClinVar variants
5
Pathogenic / LP
0.00
pLI score
7
Active trials
Clinical Summary— PRSS1
🧬
Gene-Disease Validity (ClinGen)
hereditary chronic pancreatitis · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 207 VUS of 287 total submissions
💊
Clinical Trials
7 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.86LOEUF
pLI 0.000
Z-score -0.94
OE 1.31 (0.86–1.86)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-2.01Z-score
OE missense 1.50 (1.33–1.69)
194 obs / 129.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.31 (0.86–1.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.50 (1.33–1.69)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.56
0≤1.21.6
LoF obs/exp: 14 / 10.7Missense obs/exp: 194 / 129.7Syn Z: -3.10

ClinVar Variant Classifications

287 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
VUS207
Likely Benign68
Benign3
Conflicting4
5
Pathogenic
207
VUS
68
Likely Benign
3
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
0
0
0
VUS
6
183
16
2
207
Likely Benign
0
2
8
58
68
Benign
0
0
3
0
3
Conflicting
—4
Total61853260287

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PRSS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — PRSS1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SPINK1, PRSS1, CTRC, and CFTR Genotypes Influence Disease Onset and Clinical Outcomes in Chronic Pancreatitis.
Zou WB et al.·Clin Transl Gastroenterol
2018
Expanding ACMG variant classification guidelines into a general framework.
Masson E et al.·Hum Genomics
2022
Longitudinal integrative cell-free DNA analysis in gestational diabetes mellitus.
Tang Z et al.·Cell Rep Med
2024Natural history
AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review.
Aslanian HR et al.·Gastroenterology
2020Review
Hereditary pancreatic cancer.
Abe K et al.·Int J Clin Oncol
2021Review
Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond.
Hansford S et al.·JAMA Oncol
2015
A conservative assessment of the major genetic causes of idiopathic chronic pancreatitis: data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR genes in 253 young French patients.
Masson E et al.·PLoS One
2013Cohort
Clinical interpretation of PRSS1 variants in patients with pancreatitis.
Girodon E et al.·Clin Res Hepatol Gastroenterol
2021Review
Human cationic trypsinogen (PRSS1) variants and chronic pancreatitis.
Németh BC et al.·Am J Physiol Gastrointest Liver Physiol
2014Review
Hereditary chronic pancreatitis.
Teich N et al.·Best Pract Res Clin Gastroenterol
2008Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A Case of Pancreatic Ductal Adenocarcinoma in PRSS1-Associated Hereditary Pancreatitis in the Absence of High-Grade PanIN: Suggestive of Chromothripsis-Like Tumor Evolution.
Norose T et al.·Pathol Int
2025
Case Report: a family report of hereditary pancreatitis caused by SPINK1 and PRSS1 gene mutations.
Xu J et al.·Front Genet
2025🔓 Open AccessCase report
PRSS1, SPINK1 Mutations and Associated Factors in Vietnamese Patients With Chronic Pancreatitis.
Vo TTL et al.·JGH Open
2025🔓 Open AccessCohort
Next generation sequencing misguided the clinical interpretation of the PRSS1 variant in pediatric pancreatitis: a case report.
Liu Y et al.·Front Pediatr
2025🔓 Open AccessCase report
Assessment of the Relationship of Cationic Trypsinogen (PRSS1) Gene Polymorphism with Prediabetes and Type 2 Diabetes in the Bangladeshi Population.
Parial R et al.·Indian J Endocrinol Metab
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Pancreas CancerPancreas CystPancreatic Ductal Adenocarcinoma

Pancreatic Cancer Early Detection Consortium

RECRUITING
NCT04970056Arbor Research Collaborative for HealthStarted 2020-09-18
Hereditary PancreatitisPRSS1 Gene Mutation

French National Cohort of Patients With PRSS1 Mutations

RECRUITING
NCT07413029Assistance Publique - Hôpitaux de ParisStarted 2024-11-10
collecting their health data from their medical file and completing questionnaires.
Hereditary Pancreatic Cancer

The PREPAIRD Study: Personalized Surveillance for Early Detection of Pancreatic Cancer in High Risk Individuals

ENROLLING BY INVITATION
NCT05740111Phase NAOslo University HospitalStarted 2022-09-01
Annual surveillance
Pancreas CancerExosomesExtracellular Vesicles

ExoLuminate Study for Early Detection of Pancreatic Cancer

RECRUITING
NCT05625529Biological DynamicsStarted 2022-12-19
Pancreas CancerPeutz-Jeghers Syndrome (PJS)Gene Mutation

The Cancer of the Pancreas Screening-5 CAPS5)Study

RECRUITING
NCT02000089Phase PHASE3Johns Hopkins UniversityStarted 2014-01-06
SecretinMRITumor marker gene test with CA19-9
Pancreatic CancerPancreatic Ductal AdenocarcinomaPDAC

A Prospective Registry for Patients at High-Risk for Pancreatic Cancer

RECRUITING
NCT06151223Mayo ClinicStarted 2021-07-13
Bio-specimen Collection: BloodBio-specimen Collection: Pancreatic JuiceMRI
Chronic PancreatitisGenetic MutationSmoking, Tobacco

An Observational Study on the Natural Course of Chronic Pancreatitis

ACTIVE NOT RECRUITING
NCT04574297Changhai HospitalStarted 2011-01-01
smoking and alcohol assumptiongenetic sequencing

External Resources

Links to major genomics databases and tools