PAPPA

Chr 9

pappalysin 1

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

The protein is a secreted metalloproteinase that cleaves insulin-like growth factor binding proteins (IGFBPs) to release IGF and activate the IGF pathway, playing roles in bone formation, inflammation, wound healing, and fertility. Mutations cause autosomal recessive short stature with microcephaly and distinctive facies, typically presenting in early childhood. The gene is highly constrained against loss-of-function variants (LOEUF 0.354), suggesting that complete loss of protein function has severe developmental consequences.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.35
Clinical SummaryPAPPA
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

Moderate LoF intolerance
LoF Constraint
0.35LOEUF
pLI 0.161
Z-score 6.01
OE 0.24 (0.160.35)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.21Z-score
OE missense 0.79 (0.740.84)
710 obs / 896.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.24 (0.160.35)
00.351.4
Missense OE0.79 (0.740.84)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 17 / 72.1Missense obs/exp: 710 / 896.6Syn Z: 0.09

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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