PRSS33

Chr 16

serine protease 33

Also known as: EOS

The protein is a serine protease with amidolytic activity that cleaves substrates before arginine residues and is involved in proteolysis. Mutations in this gene have been associated with developmental disorders, though the specific phenotypic spectrum and inheritance pattern require further clinical characterization. The gene shows minimal constraint against loss-of-function variants (very low pLI score), suggesting tolerance to such mutations.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.44
Clinical SummaryPRSS33
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.44LOEUF
pLI 0.000
Z-score 0.42
OE 0.87 (0.551.44)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.78Z-score
OE missense 0.83 (0.720.95)
139 obs / 167.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.87 (0.551.44)
00.351.4
Missense OE0.83 (0.720.95)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 11 / 12.6Missense obs/exp: 139 / 167.6Syn Z: 1.01
DN
0.7132th %ile
GOF
0.6931th %ile
LOF
0.3452th %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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PRSS33 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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