HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PLAA
phospholipase A2 activating protein
Chromosome 9 Β· 9p21.2
NCBI Gene: 9373Ensembl: ENSG00000137055.16HGNC: HGNC:9043UniProt: Q9Y263
88PubMed Papers
21Diseases
0Drugs
13Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cytosolcellular response to lipopolysaccharideprotein bindingmacroautophagyneurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomaliesMicrocephaly - brain defect - spasticity - hypernatremiagenetic disorderEpileptic encephalopathy
✦AI Summary

PLAA (phospholipase A2 activating protein) is a multifunctional ubiquitin-binding protein that regulates protein trafficking and degradation. As a key component of the VCP/p97 interactome, PLAA mediates ubiquitin-dependent sorting of membrane proteins to late endosomes via ESCRT-dependent mechanisms and promotes synaptic vesicle recycling 1. Beyond protein degradation pathways, PLAA regulates P-body assembly through its intrinsically disordered region, enabling mRNA processing and decapping complex recruitment 2. PLAA positively regulates cytosolic phospholipase A2 activity in response to TNF-Ξ± and lipopolysaccharide, controlling prostaglandin E2 biosynthesis 3. The protein also participates in lysophagy, facilitating clearance of damaged lysosomes during lysosomal membrane permeabilization 4. Clinically, PLAA mutations cause neurodevelopmental disorders with progressive microcephaly, spasticity, and brain anomalies 1. De novo missense variants in the PUL domain impair PLAA-p97/VCP interaction, leading to abnormal vesicle recycling and neurological phenotypes including intellectual disability, autism spectrum disorders, and psychomotor regression 15. Additionally, PLAA downregulation in ovarian cancer associates with enhanced metastasis through dysregulation of the METTL3-TRPC3 axis 6, highlighting PLAA's emerging role in cancer progression.

Sources cited
1
PLAA interacts with p97/VCP through its PUL domain to modulate synaptic vesicle recycling; de novo missense variants cause neurodevelopmental disorders with intellectual disability and autism
PMID: 38650658
2
PLAA regulates P-bodies through its intrinsically disordered region by recruiting the mRNA decapping complex regulatory subunit DCAP-1
PMID: 40560612
3
PLAA enhances cisplatin-induced apoptosis by activating phospholipase A2 and promoting mitochondrial damage
PMID: 19258036
4
PLAA participates in lysophagy by facilitating clearance of damaged lysosomes during lysosomal membrane permeabilization
PMID: 39744815
5
PLAA suppresses ovarian cancer metastasis by inhibiting METTL3 expression and reducing intracellular calcium levels
PMID: 35869392
6
PLAA variants were identified in patients with developmental delay and autism through whole-exome sequencing
PMID: 30755392
Disease Associationsβ“˜21
neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomaliesOpen Targets
0.77Strong
Microcephaly - brain defect - spasticity - hypernatremiaOpen Targets
0.51Moderate
genetic disorderOpen Targets
0.45Moderate
Epileptic encephalopathyOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.37Weak
gestational diabetesOpen Targets
0.28Weak
neoplasmOpen Targets
0.09Suggestive
ovarian cancerOpen Targets
0.08Suggestive
spinocerebellar ataxia type 35Open Targets
0.06Suggestive
Spinocerebellar ataxia type 40Open Targets
0.06Suggestive
spinocerebellar ataxia type 15/16Open Targets
0.06Suggestive
Adult-onset autosomal recessive cerebellar ataxiaOpen Targets
0.06Suggestive
spinocerebellar ataxia type 12Open Targets
0.06Suggestive
spastic ataxia 2Open Targets
0.06Suggestive
aneurysmOpen Targets
0.06Suggestive
spinocerebellar ataxia type 37Open Targets
0.06Suggestive
spinocerebellar ataxia type 20Open Targets
0.06Suggestive
X-linked intellectual disability, Hedera typeOpen Targets
0.05Suggestive
dystonia 23Open Targets
0.05Suggestive
Young adult-onset ParkinsonismOpen Targets
0.05Suggestive
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomaliesUniProt
Pathogenic Variants13
NM_001031689.3(PLAA):c.1570C>T (p.Arg524Ter)Likely pathogenic
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies
β˜…β˜…β˜†β˜†2022β†’ Residue 524
NM_001031689.3(PLAA):c.802C>T (p.Arg268Ter)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2024β†’ Residue 268
NM_001031689.3(PLAA):c.850_860del (p.Asp284fs)Likely pathogenic
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies
β˜…β˜†β˜†β˜†2022β†’ Residue 284
NM_001031689.3(PLAA):c.240_241insTAG (p.Pro81Ter)Pathogenic
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies
β˜…β˜†β˜†β˜†2019β†’ Residue 81
NM_001031689.3(PLAA):c.2350del (p.Lys783_Val784insTer)Likely pathogenic
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies
β˜…β˜†β˜†β˜†2019β†’ Residue 783
NM_001031689.3(PLAA):c.120C>G (p.Asp40Glu)Pathogenic
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies
β˜…β˜†β˜†β˜†β†’ Residue 40
NM_001031689.3(PLAA):c.1800G>A (p.Trp600Ter)Likely pathogenic
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies
β˜…β˜†β˜†β˜†β†’ Residue 600
NM_001031689.3(PLAA):c.829T>C (p.Cys277Arg)Pathogenic
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies
β˜†β˜†β˜†β˜†2020β†’ Residue 277
NM_001031689.3(PLAA):c.1049A>T (p.Glu350Val)Pathogenic
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies
β˜†β˜†β˜†β˜†2020β†’ Residue 350
NM_001031689.3(PLAA):c.68G>T (p.Gly23Val)Pathogenic
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies
β˜†β˜†β˜†β˜†2017β†’ Residue 23
NM_001031689.3(PLAA):c.2254C>T (p.Leu752Phe)Pathogenic
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies
β˜†β˜†β˜†β˜†2017β†’ Residue 752
NM_001031689.3(PLAA):c.68dup (p.Leu24fs)Pathogenic
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies
β˜†β˜†β˜†β˜†2017β†’ Residue 24
NM_001031689.3(PLAA):c.861T>A (p.Val287=)Pathogenic
not provided
β˜†β˜†β˜†β˜†β†’ Residue 287
View on ClinVar β†—
Related Genes
NPLOC4Protein interaction100%UBXN1Protein interaction100%UBXN7Protein interaction100%NSFL1CProtein interaction100%UBE4AProtein interaction99%YOD1Protein interaction99%
Tissue Expression6 tissues
Brain
100%
Heart
93%
Bone Marrow
71%
Lung
50%
Liver
49%
Ovary
33%
Gene Interaction Network
Click a node to explore
PLAANPLOC4UBXN1UBXN7NSFL1CUBE4AYOD1
PROTEIN STRUCTURE
Preparing viewer…
PDB3EBB Β· 1.90 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.68LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.49 [0.36–0.68]
RankingsWhere PLAA stands among ~20K protein-coding genes
  • #5,437of 20,598
    Most Researched88
  • #2,592of 5,498
    Most Pathogenic Variants13
  • #5,033of 17,882
    Most Constrained (LOEUF)0.68
Genes detectedPLAA
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants.
PMID: 30755392
Cold Spring Harb Mol Case Stud Β· 2019
1.00
2
Linear ubiquitination at damaged lysosomes induces local NFKB activation and controls cell survival.
PMID: 39744815
Autophagy Β· 2025
0.90
3
Identification and molecular cloning of a gene encoding Phospholipase A2 (plaA) from Aspergillus nidulans.
PMID: 16051517
Biochim Biophys Acta Β· 2005
0.80
4
Allelic heterogeneity and abnormal vesicle recycling in
PMID: 38650658
Front Mol Neurosci Β· 2024
0.70
5
PLAA/UFD-3 regulates P-bodies through its intrinsic disordered domain.
PMID: 40560612
Proc Natl Acad Sci U S A Β· 2025
0.60