PI16

Chr 6

peptidase inhibitor 16

Also known as: CD364, CRISP9, MSMBBP, PSPBP

NCBI Gene: 221476ENSG00000164530UniProt: Q6UXB8

Predicted to enable peptidase inhibitor activity. Predicted to act upstream of or within negative regulation of cell growth involved in cardiac muscle cell development. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

{Prostate cancer, hereditary, 13}MIM #611928
72
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PI16
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 59 VUS of 72 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.
1.31LOEUF
pLI 0.000
Z-score 0.60
OE 0.84 (0.55–1.31)
Tolerant

Highly tolerant — LoF variants common in population

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.
1.05Z-score
OE missense 0.82 (0.74–0.92)
227 obs / 276.3 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.0.84 (0.55–1.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.74–0.92)
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.0.93
0≤1.21.6
LoF obs/exp: 14 / 16.7Missense obs/exp: 227 / 276.3Syn Z: 0.62

ClinVar Variant Classifications

72 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS59
Likely Benign5
7
Pathogenic
1
Likely Pathogenic
59
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
0
55
4
0
59
Likely Benign
0
4
1
0
5
Benign
0
0
0
0
0
Total05913072

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

View in ClinVar →

Protein Context — Lollipop Plot

PI16 · 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

{Prostate cancer, hereditary, 13}

MIM #611928

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Cross-tissue human fibroblast atlas reveals myofibroblast subtypes with distinct roles in immune modulation.
Gao Y et al.·Cancer Cell
2024
TWIST1+FAP+ fibroblasts in the pathogenesis of intestinal fibrosis in Crohn's disease.
Zhang Y et al.·J Clin Invest
2024
Exome-wide association study identifies KDELR3 mutations in extreme myopia.
Yuan J et al.·Nat Commun
2024
Fibroblast-derived PI16 sustains inflammatory pain via regulation of CD206(+) myeloid cells.
Garrity R et al.·Brain Behav Immun
2023
Fibroblast Subpopulations in Systemic Sclerosis: Functional Implications of Individual Subpopulations and Correlations with Clinical Features.
Zhu H et al.·J Invest Dermatol
2024Functional
PI16 attenuates response to sorafenib and represents a predictive biomarker in hepatocellular carcinoma.
Wang P et al.·Cancer Med
2020
PI16 is expressed by a subset of human memory Treg with enhanced migration to CCL17 and CCL20.
Nicholson IC et al.·Cell Immunol
2012
High-resolution subtyping of fibroblasts in gastric cancer reveals diversity among fibroblast subsets and an association between the MFAP5-fibroblast subset and immunotherapy.
Wang H et al.·Front Immunol
2024
Residual homing of α4β7-expressing β1(+)PI16(+) regulatory T cells with potent suppressive activity correlates with exposure-efficacy of vedolizumab.
Becker E et al.·Gut
2022
Differential cellular origins of the extracellular matrix of tumor and normal tissues according to colorectal cancer subtypes.
Lee HJ et al.·Br J Cancer
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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