PAPPA2: Pappalysin 2 Gene
A metalloproteinase involved in insulin-like growth factor (IGF) bioavailability and growth regulation
Gene Information Card
| Symbol | PAPPA2 |
|---|---|
| Full Name | pappalysin 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q25.2 |
| NCBI Gene ID | 60676 ncbi.nlm.nih.gov/gene/60676 |
| Ensembl ID | ENSG00000116183 |
| UniProt ID | Q9BXP8 |
| OMIM ID | 606226 |
| HGNC ID | 14663 |
| Aliases | PAPP-A2, PAPP-E, PLAC3 |
Description
PAPPA2 (pappalysin 2) encodes a secreted metalloproteinase that specifically cleaves insulin-like growth factor binding protein 5 (IGFBP-5), thereby releasing IGF-I and IGF-II from their binding complexes. This proteolytic activity increases local IGF bioavailability, promoting growth and development. PAPPA2 is predominantly expressed in the placenta, ovary, and bone, and plays a critical role in postnatal linear growth. Loss-of-function mutations cause autosomal recessive short stature with elevated circulating IGF-I and IGFBP-5 levels.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Short stature due to PAPPA2 deficiency (OMIM #619489) | Loss-of-function mutations impair IGFBP-5 cleavage, reducing IGF bioavailability and causing growth failure. | Multiple reports in ClinVar and OMIM; confirmed by functional studies. |
| Intrauterine growth restriction (IUGR) | Reduced PAPPA2 expression in placenta limits IGF release, contributing to fetal growth restriction. | Case-control studies; placental expression data. |
| Osteoporosis (potential association) | Altered IGFBP-5 proteolysis may affect bone matrix turnover and mineralization. | GWAS and candidate gene studies; moderate evidence. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Placenta | 45.2 | High |
| Ovary | 12.8 | Medium |
| Bone | 8.5 | Medium |
| Kidney | 3.1 | Low |
| Liver | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (umbilical vein endothelial) | 22.4 | High expression |
| hTERT-HM (mammary epithelial) | 6.7 | Moderate |
| MCF7 (breast cancer) | 3.5 | Low |
| HeLa (cervical cancer) | 1.8 | Very low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1927C>T (p.Arg643*) | Nonsense | Rare (MAF <0.01%) | Loss of function; truncated protein lacking catalytic domain. |
| c.305C>T (p.Pro102Leu) | Missense | Rare | Reduced proteolytic activity; associated with short stature. |
| c.1118G>A (p.Arg373His) | Missense | Rare | Impaired IGFBP-5 cleavage; reported in familial short stature. |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that abolish or severely reduce IGFBP-5 proteolysis, leading to decreased IGF bioavailability and growth impairment.
Gain of Function (GOF)
Not reported in PAPPA2.
Dominant Negative (DN)
Not reported; PAPPA2 functions as a homodimer, but dominant-negative effects have not been documented.
View complete mutation data：
Gene Ontology (GO)
Pathways
• IGF-IGFBP axis (Reactome: R-HSA-381866)
• Metalloproteinase-mediated IGFBP cleavage (Reactome: R-HSA-1474228)
Protein Summary
PAPPA2 is a 1,791-amino-acid secreted metalloproteinase belonging to the pappalysin family. It contains a zinc-binding catalytic domain and multiple complement control protein (CCP) modules. The enzyme specifically cleaves IGFBP-5, and to a lesser extent IGFBP-3, liberating IGFs to bind their receptors. PAPPA2 is essential for normal postnatal growth; deficiency results in short stature with elevated serum IGF-I and IGFBP-5. The protein is also implicated in placental function and bone metabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PAPPA2 Knockout HEK293 Cell Line | EDJ-KQ13887 | Human | 60676 | 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 |
| PAPPA2 Knockout HCT 116 Cell Line | EDJ-KQ73927 | Human | 60676 | Details Get a Quote |
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