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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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PRSS1
serine protease 1
Chromosome 7 Β· 7q34
NCBI Gene: 5644Ensembl: ENSG00000204983.15HGNC: HGNC:9475UniProt: P07477
251PubMed Papers
1Diseases
0Drugs
16Pathogenic Variants
FUNCTIONAL ROLE
Protease
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
extracellular matrixblood microparticleproteolysisGO:0005615Pancreatitis, hereditary
✦AI Summary

PRSS1 encodes cationic trypsinogen, a serine protease with endopeptidase activity against multiple synthetic substrates, with the single-chain form demonstrating greater activity than the two-chain form 1. As a secreted enzyme, PRSS1 functions in protein digestion and extracellular matrix proteolysis within the pancreas 2. Pathogenic PRSS1 variants cause hereditary pancreatitis through gain-of-function mechanisms. Most high-penetrance variants increase intrapancreatic trypsin activity by enhancing trypsinogen autoactivation and/or inhibiting chymotrypsin C-mediated degradation, while others induce trypsinogen misfolding causing endoplasmic reticulum stress 1. The R122H mutation exemplifies this, promoting pancreatic inflammation and exacerbating acute and chr7 pancreatitis induced by multiple triggers including lipopolysaccharide, ethanol, and high-fat diet 3. Clinically, approximately 1% of chr7 pancreatitis patients carry PRSS1 mutations associated with hereditary pancreatitis 2. PRSS1 variants are classified as disease-causing genes (distinct from disease-predisposing genes like CFTR), and mutation-positive patients show significantly earlier disease onset and faster progression to pancreatic complications including diabetes and steatorrhea 4. Beyond pancreatic disease, emerging evidence suggests PRSS1 differential expression may serve as a biomarker in gestational diabetes mellitus 5. Additionally, PRSS1 has been identified as a regulatory protein in innate immunity, where L-alanine-mediated PRSS1 inhibition affects NF-ΞΊB pathway activation relevant to antimicrobial defense 6.

Sources cited
1
PRSS1 mutations cause approximately 1% of chronic pancreatitis cases, classified as hereditary pancreatitis
PMID: 31860051
2
PRSS1 pathogenic variants significantly influence age of disease onset and clinical outcomes in chronic pancreatitis patients
PMID: 30420730
3
PRSS1 encodes cationic trypsinogen; pathogenic variants increase intrapancreatic trypsin activity through enhanced autoactivation and/or impaired degradation
PMID: 24458023
4
PRSS1-R122H mutation promotes pancreatic inflammation and increases severity of pancreatitis induced by multiple triggers
PMID: 31419436
5
PRSS1 differential coverage emerges as a valuable biomarker for gestational diabetes mellitus
PMID: 39059385
6
PRSS1 regulates NF-ΞΊB pathway activation through interaction with L-alanine and TAK1/TAB1 complex formation in innate immunity
PMID: 38760394
Disease Associationsβ“˜1
Pancreatitis, hereditaryUniProt
Pathogenic Variants16
NM_002769.5(PRSS1):c.365G>A (p.Arg122His)Pathogenic
Hereditary pancreatitis|not provided|PRSS1-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 122
NM_002769.5(PRSS1):c.364C>T (p.Arg122Cys)Pathogenic
Hereditary pancreatitis|not provided|PRSS1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 122
NM_002769.5(PRSS1):c.47C>T (p.Ala16Val)Pathogenic
Hereditary pancreatitis|Recurrent pancreatitis|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 16
NM_002769.5(PRSS1):c.346C>T (p.Arg116Cys)Pathogenic
Hereditary pancreatitis|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 116
NM_002769.5(PRSS1):c.86A>C (p.Asn29Thr)Pathogenic
Hereditary pancreatitis
β˜…β˜…β˜†β˜†2023β†’ Residue 29
NM_002769.5(PRSS1):c.68A>G (p.Lys23Arg)Likely pathogenic
Hereditary pancreatitis
β˜…β˜…β˜†β˜†2021β†’ Residue 23
NC_000007.13:g.(?_142457132)_(142457395_?)dupPathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2021
NC_000007.13:g.(?_142457132)_(142460891_?)dupLikely pathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2021
NM_002769.5(PRSS1):c.116T>C (p.Val39Ala)Pathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2021β†’ Residue 39
NC_000007.13:g.(?_142459615)_(142460881_?)dupLikely pathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2019
NC_000007.13:g.(?_142459605)_(142460891_?)dupLikely pathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2018
NM_002769.5(PRSS1):c.416G>T (p.Cys139Phe)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2018β†’ Residue 139
NC_000007.13:g.(?_142457319)_(142460927_?)dupLikely pathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2016
NC_000007.13:g.(?_142457330)_(142460424_?)dupPathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2016
NM_002769.5(PRSS1):c.365_366delinsAT (p.Arg122His)Pathogenic
Hereditary pancreatitis
β˜†β˜†β˜†β˜†2006β†’ Residue 122
NM_002769.5(PRSS1):c.347G>C (p.Arg116Pro)Likely pathogenic
Hereditary pancreatitis
β˜†β˜†β˜†β˜†β†’ Residue 116
View on ClinVar β†—
Related Genes
TMPRSS15Protein interaction92%PLGProtein interaction91%SPINK1Protein interaction89%CPA1Protein interaction86%CTRB1Protein interaction86%PNLIPProtein interaction86%
Tissue Expression

No tissue expression data available for this gene.

Gene Interaction Network
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PRSS1TMPRSS15PLGSPINK1CPA1CTRB1PNLIP
PROTEIN STRUCTURE
Preparing viewer…
PDB2RA3 Β· 1.46 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.30LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.93 [0.67–1.30]
RankingsWhere PRSS1 stands among ~20K protein-coding genes
  • #1,530of 20,598
    Most Researched251 Β· top 10%
  • #2,381of 5,498
    Most Pathogenic Variants16
  • #13,690of 17,882
    Most Constrained (LOEUF)1.30
Genes detectedPRSS1
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
Diagnosis and Management of Chronic Pancreatitis: A Review.
PMID: 31860051
JAMA Β· 2019
1.00
2
SPINK1, PRSS1, CTRC, and CFTR Genotypes Influence Disease Onset and Clinical Outcomes in Chronic Pancreatitis.
PMID: 30420730
Clin Transl Gastroenterol Β· 2018
0.90
3
Expanding ACMG variant classification guidelines into a general framework.
PMID: 35974416
Hum Genomics Β· 2022
0.80
4
Mycobacterium tuberculosis suppresses host antimicrobial peptides by dehydrogenating L-alanine.
PMID: 38760394
Nat Commun Β· 2024
0.70
5
Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond.
PMID: 26182300
JAMA Oncol Β· 2015
0.68