PAPPA

Chr 9

pappalysin 1

Also known as: ASBABP2, DIPLA1, IGFBP-4ase, PAPA, PAPP-A, PAPPA1

NCBI Gene: 5069ENSG00000182752UniProt: Q13219

This gene encodes a secreted metalloproteinase which cleaves insulin-like growth factor binding proteins (IGFBPs). Following IGFBP cleavage, insulin growth factors dissociate from IGFBPs and bind to IGF receptors, resulting in activation of the IGF pathway. The encoded protein plays a role in bone formation, inflammation, wound healing and female fertility. Enhanced expression of this protein is associated with diabetic nephropathy in human patients and this protein may promote tumor invasion and growth in various human cancers. [provided by RefSeq, Aug 2017]

0
Active trials
0
Pathogenic / LP
0
ClinVar variants
3
Pubs (1 yr)
2.2
Missense Z
0.35
LOEUF
Clinical Summary— PAPPA
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.35LOEUF
pLI 0.161
Z-score 6.01
OE 0.24 (0.16–0.35)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
2.21Z-score
OE missense 0.79 (0.74–0.84)
710 obs / 896.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.24 (0.16–0.35)
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 (0.74–0.84)
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.0.99
0≤1.21.6
LoF obs/exp: 17 / 72.1Missense obs/exp: 710 / 896.6Syn Z: 0.09

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

PAPPA · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Pericardiotomy and Amiodarone for Prophylaxis Against Postoperative Atrial Fibrillation in Cardiac Surgery (PAPPA).
Makarem A et al.·Ann Thorac Surg
2025
CircPAPPA binds to PAPPA and promotes trophoblast proliferation in spontaneous abortion through the formation of circPAPPA-PAPPA complexes.
Zhou SY et al.·Gene
2025
Overexpression of metalloproteinase PAPPA accelerates cancer progression and correlates with immune cell infiltration in gastric cancer: insights from bioinformatics and in vitro investigations.
Yu S et al.·Cancer Cell Int
2025Open Access
Identification of Pappa and Sall3 as Gli3 direct target genes acting downstream of cilia signaling in corticogenesis.
Basu S et al.·Cereb Cortex
2024Open Access
Low PAPPA and Its Association with Adverse Pregnancy Outcomes in Twin Pregnancies: A Systematic Review of the Literature and Meta-Analysis.
Sapantzoglou I et al.·J Clin Med
2024Open AccessReview
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients