PAPPA2

Chr 1

pappalysin 2

Also known as: PAPP-A2, PAPP-E, PAPPE, PLAC3, SSDA

NCBI Gene: 60676ENSG00000116183UniProt: Q9BXP8

This gene encodes a member of the pappalysin family of metzincin metalloproteinases. The encoded protein cleaves insulin-like growth factor-binding protein 5 and is thought to be a local regulator of insulin-like growth factor (IGF) bioavailability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

ResearchGenerating clinical summary…
LOEUF 0.48
Clinical Summary— PAPPA2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 246 VUS of 333 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.48LOEUF
pLI 0.000
Z-score 5.27
OE 0.35 (0.26–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.09Z-score
OE missense 0.90 (0.86–0.95)
921 obs / 1018.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.35 (0.26–0.48)
0≤0.351.4
Missense OE?0.90 (0.86–0.95)
0≤0.61.4
Synonymous OE?0.95
0≤1.21.6
LoF obs/exp: 27 / 76.8Missense obs/exp: 921 / 1018.5Syn Z: 0.71

ClinVar Variant Classifications

333 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic2
VUS246
Likely Benign36
Benign8
Conflicting3
9
Pathogenic
2
Likely Pathogenic
246
VUS
36
Likely Benign
8
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
1
0
0
9
Likely Pathogenic
1
1
0
0
2
VUS
1
243
1
1
246
Likely Benign
0
26
1
9
36
Benign
0
0
2
6
8
Conflicting
—3
Total10271416304

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap PAPPA2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

PAPPA2 · protein map & ClinVar variants

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

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