PRSS21
Chr 16serine protease 21
Also known as: ESP-1, ESP1, TEST1, TESTISIN
The protein is a cell-surface anchored serine protease of the trypsin family that cleaves peptide bonds at lysine or arginine residues and may regulate proteolytic events during testicular germ cell maturation. This gene is highly constrained against loss-of-function variants (pLI ~0, LOEUF 1.32), but no established Mendelian diseases have been associated with PRSS21 mutations in current medical literature. The protein localizes to premeiotic testicular germ cells and may be involved in testicular tumor progression.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
PRSS21 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools