PRSS3

Chr 9

serine protease 3

Also known as: MTG, PRSS4, T9, TRY3, TRY4

NCBI Gene: 5646ENSG00000010438UniProt: P35030

This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is expressed in the brain and pancreas and is resistant to common trypsin inhibitors. It is active on peptide linkages involving the carboxyl group of lysine or arginine. This gene is localized to the locus of T cell receptor beta variable orphans on chromosome 9. Four transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2010]

114
ClinVar variants
68
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PRSS3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
68 Pathogenic / Likely Pathogenic· 9 VUS of 114 total submissions

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.
1.90LOEUF
pLI 0.000
Z-score -1.24
OE 1.41 (0.93–1.90)
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.
-0.03Z-score
OE missense 1.01 (0.89–1.15)
159 obs / 157.8 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.1.41 (0.93–1.90)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.89–1.15)
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.0.77
0≤1.21.6
LoF obs/exp: 15 / 10.6Missense obs/exp: 159 / 157.8Syn Z: 1.44

ClinVar Variant Classifications

114 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic8
VUS9
Likely Benign2
Benign14
60
Pathogenic
8
Likely Pathogenic
9
VUS
2
Likely Benign
14
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
60
0
60
Likely Pathogenic
0
0
8
0
8
VUS
0
1
8
0
9
Likely Benign
0
0
2
0
2
Benign
0
2
11
1
14
Total0389193

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

View in ClinVar →

Protein Context — Lollipop Plot

PRSS3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Immunoassay for trypsinogen-4.
Koistinen H et al.·Anal Biochem
2022
Targeting the PRSS3-PAR2-ERK1/2 axis inhibits malignancy and regulates chemosensitivity and resistance through ferroptosis in breast cancer.
Tian R et al.·Free Radic Biol Med
2025
Understanding psoriatic disease at single-cell resolution: an update.
Do TH et al.·Curr Opin Rheumatol
2025Review
Epigenetic silencing of PRSS3 provides growth and metastasis advantage for human hepatocellular carcinoma.
Lin B et al.·J Mol Med (Berl)
2017
PRSS3 expression is associated with tumor progression and poor prognosis in epithelial ovarian cancer.
Ma R et al.·Gynecol Oncol
2015
Identifying proteomic risk factors for overall, aggressive, and early onset prostate cancer using Mendelian Randomisation and tumour spatial transcriptomics.
Desai TA et al.·EBioMedicine
2024
PRSS3 is a prognostic marker in invasive ductal carcinoma of the breast.
Qian L et al.·Oncotarget
2017
High Expression of PRSS3 Indicates Unfavorable Clinical Outcomes in Colon Adenocarcinoma.
Zhang Q et al.·Appl Immunohistochem Mol Morphol
2021Clinical trial
Host neuronal PRSS3 interacts with enterovirus A71 3A protein and its role in viral replication.
Rattanakomol P et al.·Sci Rep
2022
High-level expression of PRSS3 correlates with metastasis and poor prognosis in patients with gastric cancer.
Wang F et al.·J Surg Oncol
2019Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools