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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PPFIA2
PPFI scaffold protein A2
Chromosome 12 · 12q21.31
NCBI Gene: 8499Ensembl: ENSG00000139220.17HGNC: HGNC:9246UniProt: B7Z7Y5
39PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingdense core granule cytoskeletal transportregulation of dendritic spine developmentregulation of dendritic spine morphogenesisneurodegenerative diseasealcohol drinkingAbruptio Placentaemathematical ability
✦AI Summary

PPFIA2 encodes Liprin-α2, a scaffolding protein that plays critical roles in synaptic organization and cellular adhesion. The protein functions as a synaptic scaffold in dendritic spines, serving as an immobile postsynaptic post that recruits KIF1A-driven dense core vesicles to dendritic spines 1. PPFIA2 alters PTPRF cellular localization and induces PTPRF clustering, potentially regulating focal adhesion disassembly and localizing receptor-like tyrosine phosphatases at specific plasma membrane sites 1. The protein contains multiple functional domains including PFIH domains and three SAM domains, with regions spanning SAM1-SAM3 serving as binding domains for LAR subfamily protein tyrosine phosphatases 2. Clinically, de novo variants in PPFIA2 are associated with neurodevelopmental disorders, supported by gene constraint metrics and identification in multiple affected individuals 3. The gene shows altered expression in various pathological conditions, including increased expression in colorectal cancer where PPFIA4 serves as a prognostic marker 4, elevated expression in cannabis users correlating with decreased neuropsychological function 5, and downregulation associated with Alzheimer's disease risk in aging men 6. Additionally, PPFIA2 has been implicated as a candidate gene for high-grade myopia within the MYP3 locus 7.

Sources cited
1
PPFIA2 functions as scaffolding protein in dendritic spines and recruits KIF1A-driven dense core vesicles
PMID: 30021165
2
PPFIA2 protein structure contains PFIH and SAM domains with specific binding functions
PMID: 14612982
3
De novo variants in PPFIA2 are associated with neurodevelopmental disorders
PMID: 41044885
4
PPFIA2 expression is increased in colorectal cancer
PMID: 36605492
5
PPFIA2 expression is elevated in cannabis users and correlates with neuropsychological function
PMID: 30879928
6
PPFIA2 downregulation is associated with Alzheimer's disease risk in men
PMID: 32147245
7
PPFIA2 is a candidate gene for high-grade myopia in the MYP3 locus
PMID: 23422819
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.42Moderate
alcohol drinkingOpen Targets
0.34Weak
Abruptio PlacentaeOpen Targets
0.32Weak
mathematical abilityOpen Targets
0.28Weak
neuroinflammatory disorderOpen Targets
0.28Weak
tuberculosisOpen Targets
0.27Weak
clavicle fractureOpen Targets
0.25Weak
liver diseaseOpen Targets
0.25Weak
shoulder fractureOpen Targets
0.25Weak
ulcerative colitisOpen Targets
0.25Weak
self-injurious ideationOpen Targets
0.24Weak
pyelonephritisOpen Targets
0.23Weak
major salivary gland cancerOpen Targets
0.23Weak
type 2 diabetes mellitusOpen Targets
0.21Weak
secondary malignant neoplasmOpen Targets
0.20Weak
bone fractureOpen Targets
0.17Weak
PhlebitisOpen Targets
0.17Weak
ThrombophlebitisOpen Targets
0.17Weak
diabetic neuropathyOpen Targets
0.16Weak
obesityOpen Targets
0.13Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CASKProtein interaction100%PPP2CAProtein interaction100%RIMS1Protein interaction100%PPP2R1AProtein interaction99%LIN7AProtein interaction99%UNC13BProtein interaction93%
Tissue Expression6 tissues
Brain
100%
Ovary
7%
Heart
4%
Lung
2%
Liver
2%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PPFIA2CASKPPP2CARIMS1PPP2R1ALIN7AUNC13B
PROTEIN STRUCTURE
Preparing viewer…
PDB7D2E · 1.70 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.36Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.27 [0.20–0.36]
RankingsWhere PPFIA2 stands among ~20K protein-coding genes
  • #10,377of 20,598
    Most Researched39
  • #1,634of 17,882
    Most Constrained (LOEUF)0.36 · top 10%
Genes detectedPPFIA2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Identification of a Candidate Gene Panel for the Early Diagnosis of Prostate Cancer.
PMID: 25788493
Clin Cancer Res · 2015
1.00
2
Identification and characterization of human PPFIA4 gene in silico.
PMID: 14612982
Int J Mol Med · 2003
0.90
3
De Novo Variants in PPFIA2 in Individuals With Neurodevelopmental Disorders.
PMID: 41044885
Am J Med Genet A · 2026
0.80
4
SNAP25 variant I67N: synaptic phenotypes, drug response and proteome changes in human neurons.
PMID: 40181518
Brain · 2025
0.70
5
Clinicopathological Significances and Prognostic Value of
PMID: 36605492
J Cancer · 2023
0.60