PPFIA2
Chr 12PPFI scaffold protein A2
The protein is a scaffolding protein that regulates the localization of receptor-like tyrosine phosphatases and recruits vesicles to dendritic spines, playing a critical role in synaptic function. Mutations cause autosomal dominant neurodevelopmental disorders affecting brain function. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to cause significant clinical effects.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
153 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 9 | 0 | 9 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 109 | 9 | 0 | 118 |
Likely Benign | 0 | 1 | 0 | 3 | 4 |
Benign | 0 | 1 | 2 | 1 | 4 |
| Total | 0 | 111 | 21 | 4 | 136 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PPFIA2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools