DPP3

Chr 11

dipeptidyl peptidase 3

Also known as: DPPIII

NCBI Gene: 10072ENSG00000254986UniProt: Q9NY33

This gene encodes a protein that is a member of the M49 family of metallopeptidases. This cytoplasmic protein binds a single zinc ion with its zinc-binding motif (HELLGH) and has post-proline dipeptidyl aminopeptidase activity, cleaving Xaa-Pro dipeptides from the N-termini of proteins. Increased activity of this protein is associated with endometrial and ovarian cancers. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2012]

165
ClinVar variants
13
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— DPP3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 140 VUS of 165 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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 2.54
OE 0.57 (0.41–0.81)
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.
1.29Z-score
OE missense 0.83 (0.77–0.91)
387 obs / 465.1 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.0.57 (0.41–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.77–0.91)
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.0.94
0≤1.21.6
LoF obs/exp: 23 / 40.4Missense obs/exp: 387 / 465.1Syn Z: 0.62

ClinVar Variant Classifications

165 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic3
VUS140
Likely Benign1
Benign10
Conflicting1
10
Pathogenic
3
Likely Pathogenic
140
VUS
1
Likely Benign
10
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
3
0
3
VUS
1
132
7
0
140
Likely Benign
0
0
0
1
1
Benign
0
3
3
4
10
Conflicting
—1
Total1135235165

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

View in ClinVar →

Protein Context — Lollipop Plot

DPP3 · 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
Involvement of DPP3 in modulating oncological features and oxidative stress response in esophageal squamous cell carcinoma.
Arora M et al.·Biosci Rep
2023
An outlook on biomarkers in cardiogenic shock.
Iborra-Egea O et al.·Curr Opin Crit Care
2020Review
DPP3 promotes breast cancer tumorigenesis by stabilizing FASN and promoting lipid synthesis.
Fu X et al.·Acta Biochim Biophys Sin (Shanghai)
2024
Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women.
Menale C et al.·Molecules
2022
Novel Methods for the Quantification of Dipeptidyl Peptidase 3 (DPP3) Concentration and Activity in Human Blood Samples.
Rehfeld L et al.·J Appl Lab Med
2019
Absence of Dipeptidyl Peptidase 3 Increases Oxidative Stress and Causes Bone Loss.
Menale C et al.·J Bone Miner Res
2019
Dipeptidyl peptidase 3, a marker of the antagonist pathway of the renin-angiotensin-aldosterone system in patients with heart failure.
Boorsma EM et al.·Eur J Heart Fail
2021Cohort
Method Validation of Dipeptidyl Peptidase 3 Assay.
Donato LJ et al.·J Appl Lab Med
2026
Biomarker guided immunomodulatory precision medicine to improve prognostic, predictive and adaptive enrichment strategies in sepsis trials.
Alevizou A et al.·Expert Rev Mol Diagn
2025Review
Bio-Adrenomedullin and Dipeptidyl Peptidase 3 as Novel Sepsis Biomarkers in the Emergency Department and the Intensive Care Unit: A Narrative Review.
Ventoulis I et al.·Medicina (Kaunas)
2025Review
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
Osteoarthritis, Knee

Immuno-based Profiling of knEe OA Patients to Predict reSponse to Regenerative Treatment

RECRUITING
NCT06384040Istituto Clinico HumanitasStarted 2021-11-01
platelet-rich plasma knee injection

External Resources

Links to major genomics databases and tools