PRSS16

Chr 6

serine protease 16

Also known as: TSSP

NCBI Gene: 10279ENSG00000112812UniProt: Q9NQE7

This gene encodes a serine protease expressed exclusively in the thymus. It is thought to play a role in the alternative antigen presenting pathway used by cortical thymic epithelial cells during the positive selection of T cells. The gene is found in the large histone gene cluster on chromosome 6, near the major histocompatibility complex (MHC) class I region. A second transcript variant has been described, but its full length nature has not been determined. [provided by RefSeq, Jul 2008]

82
ClinVar variants
4
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PRSS16
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
4 Pathogenic / Likely Pathogenic· 76 VUS of 82 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.
0.81LOEUF
pLI 0.000
Z-score 2.33
OE 0.53 (0.35–0.81)
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.
1.25Z-score
OE missense 0.79 (0.71–0.89)
232 obs / 292.2 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.0.53 (0.35–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.71–0.89)
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.0.79
0≤1.21.6
LoF obs/exp: 15 / 28.4Missense obs/exp: 232 / 292.2Syn Z: 1.84

ClinVar Variant Classifications

82 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
VUS76
Likely Benign1
Benign1
4
Pathogenic
76
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
0
0
0
VUS
0
72
4
0
76
Likely Benign
0
1
0
0
1
Benign
0
0
1
0
1
Total0739082

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

View in ClinVar →

Protein Context — Lollipop Plot

PRSS16 · 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
Expression, genomic structure and mapping of the thymus specific protease prss16: a candidate gene for insulin dependent diabetes mellitus susceptibility.
Cheunsuk S et al.·J Autoimmun
2002
Gene signature based on degradome-related genes can predict distal metastasis in cervical cancer patients.
Fernandez-Retana J et al.·Tumour Biol
2017Cohort
The clinicopathological significance of thymic epithelial markers expression in thymoma and thymic carcinoma.
Li H et al.·BMC Cancer
2023
[Mechanism of pregnancy-induced thymus involution and regeneration and medication rules of postpartum prescriptions].
Shu YY et al.·Zhongguo Zhong Yao Za Zhi
2023Functional
Heterozygous FOXN1 Variants Cause Low TRECs and Severe T Cell Lymphopenia, Revealing a Crucial Role of FOXN1 in Supporting Early Thymopoiesis.
Bosticardo M et al.·Am J Hum Genet
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Schizophrenia‑associated microRNA‑148b‑3p regulates COMT and PRSS16 expression by targeting the ZNF804A gene in human neuroblastoma cells.
Wu S et al.·Mol Med Rep
2020🔓 Open Access
A novel actor in antitumoral immunity: The thymus-specific serine protease TSSP/PRSS16 involved in CD4+ T-cell maturation.
Brisson L et al.·Oncoimmunology
2015🔓 Open Access
The thymus-specific serine protease TSSP/PRSS16 is crucial for the antitumoral role of CD4(+) T cells.
Brisson L et al.·Cell Rep
2015
No associations found between the genes situated at 6p22.1, HIST1H2BJ, PRSS16, and PGBD1 in Japanese patients diagnosed with schizophrenia.
Kitazawa M et al.·Am J Med Genet B Neuropsychiatr Genet
2012Cohort
ZNF804a regulates expression of the schizophrenia-associated genes PRSS16, COMT, PDE4B, and DRD2.
Girgenti MJ et al.·PLoS One
2012🔓 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.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools