PRSS3

Chr 9

serine protease 3

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

NCBI Gene: 5646 ENSG00000010438 UniProt: P35030 OMIM: 613578

This gene encodes a trypsinogen, a digestive serine protease that cleaves proteins preferentially after arginine residues and has activity against Kunitz-type trypsin inhibitors. Mutations cause hereditary pancreatitis with autosomal dominant inheritance, typically presenting with recurrent episodes of abdominal pain beginning in childhood or adolescence. The gene is not highly constrained against loss-of-function variants, consistent with pancreatitis being the primary manifestation rather than a severe multisystem disorder.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.90

LOEUF

Mechanism· predicted

📖

GeneReview available — PRSS3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.03Z-score

OE missense 1.01 (0.89–1.15)

159 obs / 157.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.41 (0.93–1.90)

0≤0.351.4

Missense OE?1.01 (0.89–1.15)

0≤0.61.4

Synonymous OE?0.77

0≤1.21.6

LoF obs/exp: 15 / 10.6Missense obs/exp: 159 / 157.8Syn Z: 1.44

Background carrier burden — how many people carry a rare variant somewhere in PRSS3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

299 rare PASS variants

Rare truncating (LoF)

1 in 500

49 rare PASS variants

Rare synonymous (reference)

1 in 350

114 rare PASS variants

Rare missense and truncating variants are carried at similar rates in PRSS3; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 320
South Asian	~43k	1 in 74	1 in 470
Remaining (unassigned)	~30k	1 in 150	1 in 2,800
European (Finnish)	~27k	1 in 380	1 in 500
Admixed American	~22k	1 in 83	none seen
African / African American	~21k	1 in 74	1 in 890
East Asian	~20k	1 in 150	1 in 280
Ashkenazi Jewish	~13k	1 in 270	1 in 670
Middle Eastern	~2,884	1 in 130	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓