PAPPA
Pappalysin 1 (Pregnancy-Associated Plasma Protein A)
Gene Information Card
| Symbol | PAPPA |
|---|---|
| Full Name | Pappalysin 1 (Pregnancy-Associated Plasma Protein A) |
| Gene Type | Protein-coding |
| Chromosomal Location | 9q33.1 |
| NCBI Gene ID | 5069 ncbi.nlm.nih.gov/gene/5069 |
| Ensembl ID | ENSG00000182752 |
| UniProt ID | Q13219 |
| OMIM ID | 176385 |
| HGNC ID | 8600 |
| Aliases | PAPP-A, ASBABP2, DIPLA1, IGFBP-4ase, PAPA |
Description
The PAPPA gene encodes pappalysin 1, a secreted metalloproteinase that cleaves insulin-like growth factor binding protein 4 (IGFBP-4), thereby regulating local bioavailability of insulin-like growth factors (IGFs). It is highly expressed in the placenta and is involved in fetal development, growth regulation, and pregnancy maintenance. Elevated serum levels are used as a biomarker for first-trimester aneuploidy screening. The protein also has roles in bone metabolism, atherosclerosis, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pregnancy-associated disorders (e.g., preeclampsia, fetal growth restriction) | Altered PAPPA expression affects IGFBP-4 cleavage, disrupting IGF signaling and placental function. | ClinVar, OMIM #176385 |
| Coronary artery disease | PAPPA is expressed in atherosclerotic plaques; its proteolytic activity may promote plaque instability. | NCBI Gene, PubMed |
| Ovarian cancer | Overexpression of PAPPA enhances IGF bioavailability, promoting tumor cell proliferation. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Placenta | 104.8 | High |
| Fallopian tube | 12.3 | Medium |
| Endometrium | 8.9 | Medium |
| Prostate | 6.2 | Medium |
| Kidney | 3.1 | Low |
| Liver | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 2.3 | Low expression |
| MCF7 (breast) | 1.8 | Low expression |
| A549 (lung) | 0.9 | Not detected |
| K-562 (leukemia) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.173C>T (p.Thr58Ile) | Missense | <0.01% | Unknown functional effect; rare population variant |
| c.2024G>A (p.Arg675Gln) | Missense | <0.01% | Reported in ClinVar as uncertain significance |
| c.3445C>T (p.Arg1149Cys) | Missense | <0.01% | Associated with reduced proteolytic activity in vitro |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants (e.g., p.Arg1149Cys) reduce IGFBP-4 cleavage activity.
Gain of Function (GOF)
Not well documented; overexpression in cancer may be considered gain-of-function at the expression level.
Dominant Negative (DN)
No known dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • Metalloendopeptidase activity (GO:0004222) | • Insulin-like growth factor binding (GO:0005520) |
| • Proteolysis (GO:0006508) | • Extracellular region (GO:0005576) |
| • Pregnancy (GO:0007565) |
Pathways
• Insulin-like growth factor (IGF) signaling pathway (Reactome: R-HSA-381866)
• Metalloproteinase activity (Reactome: R-HSA-1442490)
Protein Summary
Pappalysin 1 (PAPP-A) is a 1627-amino-acid secreted zinc metalloproteinase belonging to the metzincin superfamily. It is synthesized as a proenzyme and activated by proteolytic cleavage. The protein specifically cleaves IGFBP-4, releasing IGFs to bind their receptors. PAPP-A is heavily glycosylated and forms a heterotetrameric complex with the proform of eosinophil major basic protein (proMBP) in pregnancy serum. Its expression is highest in placenta, and it is used clinically as a first-trimester maternal serum marker for Down syndrome screening.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PAPPA Knockout HEK293 Cell Line | EDJ-KQ4630 | Human | 5069 | Details Get a Quote |
| PAPPA2 Knockout HEK293 Cell Line | EDJ-KQ13887 | Human | 60676 | Details Get a Quote |
| PAPPA Knockout A-549 Cell Line | EDJ-KQ28548 | Human | 5069 | Details Get a Quote |
| PAPPA Knockout HeLa Cell Line | EDJ-KQ28550 | Human | 5069 | Details Get a Quote |
| PAPPA2 Knockout HeLa Cell Line | EDJ-KQ56986 | Human | 60676 | Details Get a Quote |
| PAPPA2 Knockout A-549 Cell Line | EDJ-KQ65489 | Human | 60676 | Details Get a Quote |
| PAPPA Knockout HCT 116 Cell Line | EDJ-KQ71037 | Human | 5069 | Details Get a Quote |
| PAPPA2 Knockout HCT 116 Cell Line | EDJ-KQ73927 | Human | 60676 | Details Get a Quote |
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