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GeneE
25 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.
PLA2G6
phospholipase A2 group VI
Chromosome 22 Β· 22q13.1
NCBI Gene: 8398Ensembl: ENSG00000184381.21HGNC: HGNC:9039UniProt: O60733
185PubMed Papers
23Diseases
0Drugs
176Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
phosphatidylcholine catabolic processphosphatidylcholine lysophospholipase A1 activityA2-type glycerophospholipase activityprotein bindingneurodegeneration with brain iron accumulation 2AAdult-onset dystonia-parkinsonismautosomal recessive Parkinson disease 14neurodegeneration with brain iron accumulation 2B
✦AI Summary

PLA2G6 (phospholipase A2 group VI) encodes a calcium-independent phospholipase involved in lipid metabolism and mitochondrial homeostasis 1. The protein mediates detoxification of oxidized phospholipids by cleaving acyl tails from the glycerol backbone, converting oxidized phosphatidylethanolamine to lyso-phosphatidylethanolamine and regulating ferroptosis and mitochondrial function 23. PLA2G6 is activated by the mitochondrial protease LACTB, which cleaves and activates the phospholipase to control lipid-mediated kidney and metabolic dysfunction 2. Pathogenic PLA2G6 variants cause PLA2G6-associated neurodegeneration (PLAN), a clinically heterogeneous spectrum of autosomal recessive disorders 1. These include infantile neuroaxonal dystrophy/neurodegeneration with brain iron accumulation (NBIA) 2A, atypical neuronal dystrophy/NBIA2B, and adult-onset dystonia-parkinsonism (PARK14) 41. PLA2G6 mutations are a recognized cause of early-onset Parkinson's disease, particularly in autosomal recessive inheritance patterns 567. The pathophysiology involves mitochondrial dysfunction, Ξ±-synuclein aggregation, and impaired membrane homeostasis 1. Genetic testing is clinically important for differential diagnosis in early-onset and familial parkinsonian syndromes 8.

Sources cited
1
PLA2G6 encodes phospholipase A2 involved in membrane homeostasis, signal transduction, mitochondrial dysfunction, and Ξ±-synuclein aggregation; mutations cause PLAN spectrum including NBIA2A, NBIA2B, and PARK14
PMID: 37236368
2
LACTB is a mitochondrial protease that cleaves and activates PLA2G6; LACTB-PLA2G6 pathway converts oxidized phosphatidylethanolamine to lyso-phosphatidylethanolamine regulating mitochondrial function and ferroptosis
PMID: 39561766
3
iPLA2Ξ² (PLA2G6) mediates detoxification of peroxidized lipids by cleaving acyl tails from phospholipids and acts as a ferroptosis repressor
PMID: 34131139
4
PLA2G6 mutations cause phospholipase A2-associated neurodegeneration, one of four most common NBIA disorders
PMID: 29325618
5
PLA2G6 mutations cause atypical or complex parkinsonism and are recognized monogenic Parkinson's disease genes
PMID: 35328025
6
PLA2G6 variants contribute to early-onset Parkinson's disease risk in ethnic Chinese populations
PMID: 35861376
7
PLA2G6 pathogenic variants are associated with significantly earlier age of Parkinson's disease onset compared to non-carriers
PMID: 32613234
8
PLA2G6 variants account for 1.89% of early-onset Parkinson's disease cases and genetic testing is important for differential diagnosis
PMID: 37198191
Disease Associationsβ“˜23
neurodegeneration with brain iron accumulation 2AOpen Targets
0.85Strong
Adult-onset dystonia-parkinsonismOpen Targets
0.77Strong
autosomal recessive Parkinson disease 14Open Targets
0.73Strong
neurodegeneration with brain iron accumulation 2BOpen Targets
0.73Strong
PLA2G6-associated neurodegenerationOpen Targets
0.73Strong
Parkinson diseaseOpen Targets
0.72Strong
Iron accumulation in brainOpen Targets
0.55Moderate
neurodegeneration with brain iron accumulationOpen Targets
0.55Moderate
genetic disorderOpen Targets
0.54Moderate
Abnormality of the nervous systemOpen Targets
0.48Moderate
cutaneous melanomaOpen Targets
0.40Moderate
skin cancerOpen Targets
0.34Weak
spastic ataxiaOpen Targets
0.34Weak
cerebellar ataxiaOpen Targets
0.34Weak
Global developmental delayOpen Targets
0.33Weak
microcephalyOpen Targets
0.33Weak
Abnormal brain morphologyOpen Targets
0.33Weak
Developmental regressionOpen Targets
0.33Weak
isolated cerebellar hypoplasia/agenesisOpen Targets
0.33Weak
Subdural hemorrhageOpen Targets
0.33Weak
Neurodegeneration with brain iron accumulation 2AUniProt
Neurodegeneration with brain iron accumulation 2BUniProt
Parkinson disease 14UniProt
Pathogenic Variants176
NM_003560.4(PLA2G6):c.1186+1G>TPathogenic
not provided|Infantile neuroaxonal dystrophy|Autosomal recessive Parkinson disease 14;Infantile neuroaxonal dystrophy;Neurodegeneration with brain iron accumulation 2B
β˜…β˜…β˜†β˜†2026
NM_003560.4(PLA2G6):c.2035-926G>ALikely pathogenic
not provided|PLA2G6-associated neurodegeneration|Infantile neuroaxonal dystrophy
β˜…β˜…β˜†β˜†2026
NM_003560.4(PLA2G6):c.1799G>A (p.Arg600Gln)Pathogenic
Iron accumulation in brain|not provided|Neurodegeneration with brain iron accumulation 2B|Inborn genetic diseases|Infantile neuroaxonal dystrophy|PLA2G6-associated neurodegeneration|Infantile neuroaxonal dystrophy;Neurodegeneration with brain iron accumulation 2B;Autosomal recessive Parkinson disease 14|Neurodegeneration with brain iron accumulation|Infantile osteopetrosis with neuroaxonal dysplasia|PLA2G6-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 600
NM_003560.4(PLA2G6):c.217C>T (p.Gln73Ter)Pathogenic
not provided|Infantile neuroaxonal dystrophy
β˜…β˜…β˜†β˜†2026β†’ Residue 73
NM_003560.4(PLA2G6):c.1547_1548dup (p.Gly517fs)Pathogenic
Infantile neuroaxonal dystrophy|not provided|Neurodegeneration with brain iron accumulation
β˜…β˜…β˜†β˜†2026β†’ Residue 517
NM_003560.4(PLA2G6):c.1903C>T (p.Arg635Ter)Pathogenic
Iron accumulation in brain|not provided|PLA2G6-associated neurodegeneration|Infantile neuroaxonal dystrophy|Infantile neuroaxonal dystrophy;Neurodegeneration with brain iron accumulation 2B;Autosomal recessive Parkinson disease 14|Neurodegeneration with brain iron accumulation
β˜…β˜…β˜†β˜†2026β†’ Residue 635
NM_003560.4(PLA2G6):c.755del (p.Asn252fs)Pathogenic
Iron accumulation in brain|not provided|Infantile neuroaxonal dystrophy|PLA2G6-associated neurodegeneration|Infantile neuroaxonal dystrophy;Neurodegeneration with brain iron accumulation 2B;Autosomal recessive Parkinson disease 14
β˜…β˜…β˜†β˜†2026β†’ Residue 252
NM_003560.4(PLA2G6):c.1894C>T (p.Arg632Trp)Pathogenic
Karak syndrome|not provided|Neurodegeneration with brain iron accumulation|PLA2G6-associated neurodegeneration|Infantile neuroaxonal dystrophy|Infantile neuroaxonal dystrophy;Autosomal recessive Parkinson disease 14;Neurodegeneration with brain iron accumulation 2B
β˜…β˜…β˜†β˜†2026β†’ Residue 632
NM_003560.4(PLA2G6):c.991G>T (p.Asp331Tyr)Pathogenic
Autosomal recessive Parkinson disease 14|not provided|Infantile neuroaxonal dystrophy|PLA2G6-associated neurodegeneration|Autosomal recessive Parkinson disease 14;Infantile neuroaxonal dystrophy;Neurodegeneration with brain iron accumulation 2B
β˜…β˜…β˜†β˜†2025β†’ Residue 331
NM_003560.4(PLA2G6):c.1904G>A (p.Arg635Gln)Pathogenic
Autosomal recessive Parkinson disease 14|PLA2G6-associated neurodegeneration|not provided|Autosomal recessive Parkinson disease 14;Infantile neuroaxonal dystrophy;Neurodegeneration with brain iron accumulation 2B|Infantile neuroaxonal dystrophy
β˜…β˜…β˜†β˜†2025β†’ Residue 635
NM_003560.4(PLA2G6):c.1117G>C (p.Gly373Arg)Pathogenic
Infantile neuroaxonal dystrophy|Neurodegeneration with brain iron accumulation
β˜…β˜…β˜†β˜†2025β†’ Residue 373
NM_003560.4(PLA2G6):c.109C>T (p.Arg37Ter)Pathogenic
Infantile neuroaxonal dystrophy|Iron accumulation in brain|not provided|Neurodegeneration with brain iron accumulation 2B|PLA2G6-associated neurodegeneration|Autosomal recessive Parkinson disease 14;Infantile neuroaxonal dystrophy;Neurodegeneration with brain iron accumulation 2B
β˜…β˜…β˜†β˜†2025β†’ Residue 37
NM_003560.4(PLA2G6):c.319del (p.Leu107fs)Pathogenic
Neurodegeneration with brain iron accumulation 2B|not provided|PLA2G6-associated neurodegeneration|Infantile neuroaxonal dystrophy;Neurodegeneration with brain iron accumulation 2B;Autosomal recessive Parkinson disease 14|Infantile neuroaxonal dystrophy
β˜…β˜…β˜†β˜†2025β†’ Residue 107
NM_003560.4(PLA2G6):c.1427+1G>APathogenic
Infantile neuroaxonal dystrophy|Infantile neuroaxonal dystrophy;Neurodegeneration with brain iron accumulation 2B;Autosomal recessive Parkinson disease 14|not provided|PLA2G6-associated neurodegeneration|Familial prostate cancer
β˜…β˜…β˜†β˜†2025
NM_003560.4(PLA2G6):c.2370_2371del (p.Tyr790_Glu791delinsTer)Pathogenic
Infantile neuroaxonal dystrophy|Neurodegeneration with brain iron accumulation 2B|not provided|Iron accumulation in brain|Inborn genetic diseases|PLA2G6-associated neurodegeneration|Infantile neuroaxonal dystrophy;Autosomal recessive Parkinson disease 14;Neurodegeneration with brain iron accumulation 2B
β˜…β˜…β˜†β˜†2025β†’ Residue 790
NM_003560.4(PLA2G6):c.238G>A (p.Ala80Thr)Pathogenic
Neurodegeneration with brain iron accumulation 2B|Infantile neuroaxonal dystrophy|Infantile neuroaxonal dystrophy;Autosomal recessive Parkinson disease 14;Neurodegeneration with brain iron accumulation 2B|not provided|PLA2G6-associated neurodegeneration
β˜…β˜…β˜†β˜†2025β†’ Residue 80
NM_003560.4(PLA2G6):c.1061T>C (p.Leu354Pro)Pathogenic
Infantile neuroaxonal dystrophy|Autosomal recessive Parkinson disease 14|Neurodegeneration with brain iron accumulation 2B|Neurodegeneration with brain iron accumulation
β˜…β˜…β˜†β˜†2025β†’ Residue 354
NM_003560.4(PLA2G6):c.1435C>G (p.His479Asp)Pathogenic
Infantile neuroaxonal dystrophy|not provided|Neurodegeneration with brain iron accumulation
β˜…β˜…β˜†β˜†2025β†’ Residue 479
NM_003560.4(PLA2G6):c.2239C>T (p.Arg747Trp)Pathogenic
Autosomal recessive Parkinson disease 14|Infantile neuroaxonal dystrophy;Autosomal recessive Parkinson disease 14;Neurodegeneration with brain iron accumulation 2B|not provided|PLA2G6-associated neurodegeneration|Infantile neuroaxonal dystrophy
β˜…β˜…β˜†β˜†2025β†’ Residue 747
NM_003560.4(PLA2G6):c.673C>T (p.His225Tyr)Pathogenic
Iron accumulation in brain|not provided|Infantile neuroaxonal dystrophy
β˜…β˜…β˜†β˜†2025β†’ Residue 225
View on ClinVar β†—
Related Genes
PINK1Protein interaction99%CALML5Protein interaction96%CALML3Protein interaction96%CALML4Protein interaction96%PRKCAProtein interaction95%PTGS2Protein interaction95%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
55%
Liver
51%
Lung
41%
Brain
38%
Heart
26%
Gene Interaction Network
Click a node to explore
PLA2G6PINK1CALML5CALML3CALML4PRKCAPTGS2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O60733
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.97LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.78 [0.63–0.97]
RankingsWhere PLA2G6 stands among ~20K protein-coding genes
  • #2,332of 20,598
    Most Researched185 Β· top quartile
  • #409of 5,498
    Most Pathogenic Variants176 Β· top 10%
  • #9,226of 17,882
    Most Constrained (LOEUF)0.97
Genes detectedPLA2G6
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Monogenic Parkinson's Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing.
PMID: 35328025
Genes (Basel) Β· 2022
1.00
2
Neurodegeneration with brain iron accumulation.
PMID: 29325618
Handb Clin Neurol Β· 2018
0.90
3
Human genetics identify convergent signals in mitochondrial LACTB-mediated lipid metabolism in cardiovascular-kidney-metabolic syndrome.
PMID: 39561766
Cell Metab Β· 2025
0.80
4
Phospholipase iPLA
PMID: 33542532
Nat Chem Biol Β· 2021
0.72
5
The mutation spectrum of Parkinson-disease-related genes in early-onset Parkinson's disease in ethnic Chinese.
PMID: 35861376
Eur J Neurol Β· 2022
0.70