PLA2G6 Gene (Phospholipase A2 Group VI)
Calcium-independent phospholipase A2 beta (iPLA2β) – key roles in phospholipid remodeling, mitochondrial function, and neurodegeneration.
Gene Information Card
| Symbol | PLA2G6 |
|---|---|
| Full Name | Phospholipase A2 Group VI |
| Gene Type | Protein coding |
| Chromosomal Location | 22q13.1 |
| NCBI Gene ID | 8398 ncbi.nlm.nih.gov/gene/8398 |
| Ensembl ID | ENSG00000100360 |
| UniProt ID | O60733 |
| OMIM ID | 603604 |
| HGNC ID | 9040 |
| Aliases | iPLA2, iPLA2beta, NBIA2, PARK14, PNPLA9, PLA2G6 |
Description
PLA2G6 encodes calcium-independent phospholipase A2 beta (iPLA2β), an enzyme that catalyzes the hydrolysis of glycerophospholipids at the sn-2 position to release lysophospholipids and free fatty acids. It plays critical roles in membrane phospholipid remodeling, arachidonic acid release, cell signaling, and mitochondrial function. Loss-of-function mutations in PLA2G6 cause a spectrum of neurodegenerative disorders collectively termed PLA2G6-associated neurodegeneration (PLAN), including infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (NAD), and adult-onset dystonia-parkinsonism (PARK14).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Infantile Neuroaxonal Dystrophy (INAD) | Biallelic loss-of-function mutations lead to impaired phospholipid metabolism and axonal swelling with spheroid bodies. | ClinVar, OMIM #256600 |
| Atypical Neuroaxonal Dystrophy (NAD) | Partial loss of iPLA2β activity results in later-onset neurodegeneration with cerebellar atrophy. | ClinVar, OMIM #610217 |
| Parkinson Disease 14 (PARK14) | Missense mutations cause adult-onset levodopa-responsive dystonia-parkinsonism with cognitive decline. | ClinVar, OMIM #612953 |
| Neurodegeneration with Brain Iron Accumulation (NBIA) | PLA2G6 mutations are a major cause of NBIA, with iron deposition in basal ganglia. | OMIM #256600, #610217 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Testis | 8.7 | Medium |
| Heart | 6.5 | Low |
| Skeletal Muscle | 5.9 | Low |
| Liver | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.1 | High expression |
| HeLa (cervical carcinoma) | 9.8 | Medium |
| HEK293 (embryonic kidney) | 7.3 | Medium |
| HepG2 (hepatocellular carcinoma) | 4.5 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2222G>A (p.Arg741Gln) | Missense | <1% | Reduced enzymatic activity; associated with PARK14 |
| c.1077delG (p.Leu360Trpfs*28) | Frameshift | Rare | Loss of function; causes INAD |
| c.1634A>G (p.Tyr545Cys) | Missense | <0.5% | Impaired calcium-independent phospholipase activity; linked to atypical NAD |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein; severe INAD phenotype |
Mutation functional classification
Loss of Function (LOF)
Biallelic truncating, frameshift, and start-loss mutations cause complete or near-complete loss of iPLA2β activity, leading to infantile neuroaxonal dystrophy (INAD).
Gain of Function (GOF)
No evidence of gain-of-function mutations in PLA2G6.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg741Gln) may exert dominant-negative effects in heterozygous state, contributing to adult-onset parkinsonism.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Phospholipid metabolism (Reactome: R-HSA-1483206)
• Glycerophospholipid biosynthesis (Reactome: R-HSA-1483191)
• Arachidonic acid metabolism (KEGG: hsa00590)
• Autophagy (inferred from mitochondrial dysfunction in PLAN)
Protein Summary
The PLA2G6 protein (iPLA2β) is a 806-amino acid calcium-independent phospholipase A2 that localizes to the cytoplasm, mitochondria, and plasma membrane. It contains ankyrin repeats and a patatin-like phospholipase domain. The enzyme preferentially hydrolyzes phosphatidylcholine and phosphatidylethanolamine, releasing lysophospholipids and free fatty acids, including arachidonic acid. iPLA2β is essential for membrane homeostasis, mitochondrial integrity, and synaptic vesicle recycling. Loss of function leads to lipid dysregulation, mitochondrial dysfunction, and axonal degeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PLA2G6 Knockout HEK293 Cell Line | EDJ-KQ1270 | Human | 8398 | Details Get a Quote |
| PLA2G6 Knockout HeLa Cell Line | EDJ-KQ19299 | Human | 8398 | Details Get a Quote |
| PLA2G6 Knockout A-549 Cell Line | EDJ-KQ20648 | Human | 8398 | Details Get a Quote |
| PLA2G6 Knockout HCT 116 Cell Line | EDJ-KQ20649 | Human | 8398 | Details Get a Quote |
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