PNPLA8
Patatin-like phospholipase domain-containing protein 8 (calcium-independent phospholipase A2 gamma)
Gene Information Card
| Symbol | PNPLA8 |
|---|---|
| Full Name | Patatin-like phospholipase domain containing 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q31.33 |
| NCBI Gene ID | 50640 ncbi.nlm.nih.gov/gene/50640 |
| Ensembl ID | ENSG00000106524 |
| UniProt ID | Q9NP80 |
| OMIM ID | 612123 |
| HGNC ID | 16259 |
| Aliases | IPLA2-GAMMA, iPLA2γ, PNPLA8, MMT1 |
Description
PNPLA8 encodes calcium-independent phospholipase A2 gamma (iPLA2γ), a mitochondrial phospholipase that catalyzes the hydrolysis of membrane phospholipids to release free fatty acids and lysophospholipids. It plays a key role in mitochondrial membrane remodeling, cardiolipin metabolism, and cellular signaling. Mutations in PNPLA8 are associated with neurodegenerative disorders and metabolic diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodegeneration with brain iron accumulation (NBIA) | Loss-of-function mutations impair mitochondrial phospholipid remodeling, leading to iron accumulation and oxidative stress | ClinVar, OMIM |
| Mitochondrial myopathy | Defective iPLA2γ disrupts cardiolipin homeostasis, causing mitochondrial dysfunction | OMIM, PubMed |
| Spastic paraplegia | PNPLA8 variants linked to axonal degeneration via altered lipid signaling | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 18.3 | High |
| Skeletal muscle | 15.7 | High |
| Liver | 8.2 | Medium |
| Kidney | 10.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.0 | Neuronal model |
| HepG2 (hepatocellular carcinoma) | 9.5 | Liver model |
| HeLa (cervical carcinoma) | 7.8 | Epithelial model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1072C>T (p.Arg358*) | Nonsense | Rare | Loss of function; truncated protein |
| c.1546G>A (p.Gly516Arg) | Missense | Rare | Impaired phospholipase activity |
| c.2020_2021del (p.Leu674fs) | Frameshift | Rare | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Most PNPLA8 mutations are loss-of-function, reducing iPLA2γ activity and disrupting mitochondrial lipid metabolism.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Not described; recessive inheritance pattern suggested.
View complete mutation data：
Gene Ontology (GO)
| • phospholipase A2 activity | • calcium-independent phospholipase A2 activity |
| • mitochondrial membrane | • lipid metabolic process |
| • cardiolipin metabolic process |
Pathways
• Glycerophospholipid metabolism
• Mitochondrial phospholipid remodeling
• Arachidonic acid metabolism
Protein Summary
iPLA2γ is a 782-amino acid protein localized to the inner mitochondrial membrane. It contains a patatin-like phospholipase domain and a C-terminal transmembrane region. The enzyme preferentially hydrolyzes phosphatidylcholine and cardiolipin, contributing to mitochondrial membrane dynamics and signaling lipid production.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PNPLA8 Knockout HEK293 Cell Line | EDJ-KQ10790 | Human | 50640 | Details Get a Quote |
| PNPLA8 Knockout A-549 Cell Line | EDJ-KQ38425 | Human | 50640 | Details Get a Quote |
| PNPLA8 Knockout HCT 116 Cell Line | EDJ-KQ38426 | Human | 50640 | Details Get a Quote |
| PNPLA8 Knockout HeLa Cell Line | EDJ-KQ38427 | Human | 50640 | Details Get a Quote |
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