PRSS8

Chr 16

serine protease 8

Also known as: CAP1, PROSTASIN

NCBI Gene: 5652ENSG00000052344UniProt: Q16651

This gene encodes a member of the peptidase S1 or chymotrypsin family of serine proteases. The encoded preproprotein is proteolytically processed to generate light and heavy chains that associate via a disulfide bond to form the heterodimeric enzyme. This enzyme is highly expressed in prostate epithelia and is one of several proteolytic enzymes found in seminal fluid. This protease exhibits trypsin-like substrate specificity, cleaving protein substrates at the carboxyl terminus of lysine or arginine residues. The encoded protease partially mediates proteolytic activation of the epithelial sodium channel, a regulator of sodium balance, and may also play a role in epithelial barrier formation. [provided by RefSeq, Feb 2016]

57
ClinVar variants
14
Pathogenic / LP
0.10
pLI score
0
Active trials
Clinical Summary— PRSS8
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 37 VUS of 57 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.
0.69LOEUF
pLI 0.100
Z-score 2.37
OE 0.30 (0.15–0.69)
Tolerant

Typical tolerance to LoF variation

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.
1.17Z-score
OE missense 0.77 (0.67–0.88)
154 obs / 200.8 exp
Tolerant

Mild missense constraint

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.0.30 (0.15–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.67–0.88)
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.0.90
0≤1.21.6
LoF obs/exp: 4 / 13.3Missense obs/exp: 154 / 200.8Syn Z: 0.74

ClinVar Variant Classifications

57 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic3
VUS37
Likely Benign5
Benign1
11
Pathogenic
3
Likely Pathogenic
37
VUS
5
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
3
0
3
VUS
0
31
6
0
37
Likely Benign
0
4
0
1
5
Benign
0
1
0
0
1
Total03620157

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

View in ClinVar →

Protein Context — Lollipop Plot

PRSS8 · 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
Plasma proteomic profiles identify biomarkers predicting Crohn's disease up to 16 years before onset.
Feng J et al.·Nat Commun
2025
PRSS8 methylation and its significance in esophageal squamous cell carcinoma.
Bao Y et al.·Oncotarget
2016
PRSS8 is Downregulated and Suppresses Tumour Growth and Metastases in Hepatocellular Carcinoma.
Zhang L et al.·Cell Physiol Biochem
2016
Tumor suppressor PRSS8 targets Sphk1/S1P/Stat3/Akt signaling in colorectal cancer.
Bao Y et al.·Oncotarget
2016
Integrative multi-omics analysis identifies genetically supported druggable targets and immune cell specificity for myasthenia gravis.
Li J et al.·J Transl Med
2024
Structure and chromosomal localization of the human prostasin (PRSS8) gene.
Yu JX et al.·Genomics
1996
PRSS8, encoding prostasin, is mutated in patients with autosomal recessive ichthyosis.
Shamseldin HE et al.·Hum Genet
2023Cohort
The serine protease prostasin (PRSS8) is a potential biomarker for early detection of ovarian cancer.
Tamir A et al.·J Ovarian Res
2016
Unraveling a difficult diagnosis: the tricks for early recognition of ovarian cancer.
Giampaolino P et al.·Minerva Med
2019Review
Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value.
Hong S et al.·J Ovarian Res
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
m6A Modification Destabilizes Prss8 and Activates Hepatic Stellate Cells via TLR4-Mediated Inflammatory Responses.
Chen H et al.·DNA Cell Biol
2025
Dietary K+ supplementation restores normal aldosterone level in Na+-deprived renal tubule-specific CAP1/Prss8-deficient mice.
Ehret E et al.·Am J Physiol Renal Physiol
2025
Circ_0001741 exerts as a tumor promoter in ovarian cancer through the regulation of miR-491-5p/PRSS8 axis.
Wang D et al.·Discov Oncol
2024🔓 Open Access
Potential Plasma Proteins (LGALS9, LAMP3, PRSS8 and AGRN) as Predictors of Hospitalisation Risk in COVID-19 Patients.
McLarnon T et al.·Biomolecules
2024🔓 Open AccessCohort
YTHDF2 protein stabilization by the deubiquitinase OTUB1 promotes prostate cancer cell proliferation via PRSS8 mRNA degradation.
Zhao X et al.·J Biol Chem
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools