PLA2G6

Chr 22

phospholipase A2 group VI

Also known as: CaI-PLA2, GVI, INAD1, IPLA2-VIA, NBIA2, NBIA2A, NBIA2B, PARK14

NCBI Gene: 8398ENSG00000184381UniProt: O60733

The protein encoded by this gene is an A2 phospholipase, a class of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, fas-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only three of them have been determined to date. [provided by RefSeq, Dec 2010]

Primary Disease Associations & Inheritance

UniProtNeurodegeneration with brain iron accumulation 2B
UniProtNeurodegeneration with brain iron accumulation 2A
UniProtParkinson disease 14
589
ClinVar variants
81
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— PLA2G6
🧬
Gene-Disease Validity (ClinGen)
PLA2G6-associated neurodegeneration · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
81 Pathogenic / Likely Pathogenic· 140 VUS of 589 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.86LOEUF
pLI 0.000
Z-score 2.20
OE 0.60 (0.42–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.21Z-score
OE missense 0.85 (0.78–0.92)
425 obs / 501.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.60 (0.42–0.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.78–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.84
0≤1.21.6
LoF obs/exp: 21 / 35.1Missense obs/exp: 425 / 501.5Syn Z: 1.83

ClinVar Variant Classifications

589 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic32
VUS140
Likely Benign352
Benign5
Conflicting11
49
Pathogenic
32
Likely Pathogenic
140
VUS
352
Likely Benign
5
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
6
21
0
49
Likely Pathogenic
16
11
5
0
32
VUS
0
132
8
0
140
Likely Benign
0
16
148
188
352
Benign
0
0
5
0
5
Conflicting
—11
Total38165187188589

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PLA2G6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PLA2G6-related infantile neuroaxonal dystrophy

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — PLA2G6
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Monogenic Parkinson's Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing.
Jia F et al.·Genes (Basel)
2022Review
Neurodegeneration with brain iron accumulation.
Hayflick SJ et al.·Handb Clin Neurol
2018Review
The mutation spectrum of Parkinson-disease-related genes in early-onset Parkinson's disease in ethnic Chinese.
Chen YP et al.·Eur J Neurol
2022
The role of the PLA2G6 gene in neurodegenerative diseases.
Deng X et al.·Ageing Res Rev
2023Review
The role of genetics in Parkinson's disease: a large cohort study in Chinese mainland population.
Zhao Y et al.·Brain
2020Cohort
Dissecting the Phenotype and Genotype of PLA2G6-Related Parkinsonism.
Magrinelli F et al.·Mov Disord
2022
Autosomal recessive parkinsonism.
Bonifati V·Parkinsonism Relat Disord
2012Review
Phospholipase iPLA(2)β averts ferroptosis by eliminating a redox lipid death signal.
Sun WY et al.·Nat Chem Biol
2021
Neurodegeneration with Brain Iron Accumulation.
Schipper DA et al.·Adv Exp Med Biol
2025Review
Axonal dystrophies.
Nardocci N et al.·Handb Clin Neurol
2013Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Generation of induced pluripotent stem cells (NIMHi027-A) from a Parkinson's disease patient harbouring a homozygous missense mutation for PLA2G6 gene (chr22:g.38112558C > T).
Banerjee R et al.·Stem Cell Res
2026
Seminal plasma extracellular vesicle-derived miR-296-3p targets PLA2G6 to enhance boar sperm motility by lowering Lys Phosphatidylcholine.
Zhao K et al.·Anim Reprod Sci
2026
Adult-Onset PLA2G6-Associated Parkinsonism With Claval Hypertrophy: A Rare Radiological-Genetic Association.
Mishra B et al.·Cureus
2026🔓 Open Access
ATG9A-PLA2G6 axis reprograms phospholipid metabolism to drive metabolic liver disease and hepatocellular carcinoma.
Zhu Q et al.·Autophagy
2026
GABAergic neurons are a key cell type in a Drosophila model of PARK14/PLA2G6-associated neurodegeneration.
Meimoun NS et al.·Front Neurosci
2025🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Parkinson Disease

Aquaporin-4 Single Nucleotide Polymorphisms in Patients With Idiopathic and Familial Parkinson's Disease

ACTIVE NOT RECRUITING
NCT04553185University of ExeterStarted 2018-11-28
Study procedure

External Resources

Links to major genomics databases and tools