PRSS27

Chr 16

serine protease 27

Also known as: CAPH2, MPN

NCBI Gene: 83886 ENSG00000172382 UniProt: Q9BQR3 OMIM: 608018

The encoded protein is a secreted tryptic serine protease expressed mainly in the pancreas. Mutations in this gene cause autosomal recessive enterokinase deficiency, a rare disorder presenting in infancy with failure to thrive, diarrhea, and malabsorption due to impaired pancreatic enzyme activation. The gene is highly tolerant to loss-of-function variants in the general population (pLI = 0.00008), consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq

This gene is located within a large protease gene cluster on chromosome 16. It belongs to the group-1 subfamily of serine proteases. The encoded protein is a secreted tryptic serine protease and is expressed mainly in the pancreas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.18

Clinical Summary— PRSS27

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.18LOEUF

pLI 0.000

Z-score 1.13

OE 0.65 (0.38–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.78Z-score

OE missense 0.83 (0.73–0.96)

145 obs / 173.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.38–1.18)

0≤0.351.4

Missense OE?0.83 (0.73–0.96)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 8 / 12.3Missense obs/exp: 145 / 173.9Syn Z: 0.57

This gene — mechanism propensity

0.7228th %ile

GOF

0.6737th %ile

LOF

0.3067th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.