PLA2G6

Chr 22AR

phospholipase A2 group VI

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

NCBI Gene: 8398ENSG00000184381UniProt: O60733OMIM: 603604

This gene encodes an A2 phospholipase that catalyzes the release of fatty acids from phospholipids and functions in phospholipid remodeling, arachidonic acid release, and prostaglandin synthesis. Mutations cause autosomal recessive infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation 2B, and Parkinson disease 14. The pathogenic mechanism appears to involve gain-of-function effects.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.863 OMIM phenotypes
Clinical Summary— PLA2G6
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Gene-Disease Validity (ClinGen)
PLA2G6-associated neurodegeneration · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
63 unique Pathogenic / Likely Pathogenic· 110 VUS of 500 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — PLA2G6
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.000
Z-score 2.20
OE 0.60 (0.42–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.21Z-score
OE missense 0.85 (0.78–0.92)
425 obs / 501.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.42–0.86)
0≤0.351.4
Missense OE0.85 (0.78–0.92)
0≤0.61.4
Synonymous OE0.84
0≤1.21.6
LoF obs/exp: 21 / 35.1Missense obs/exp: 425 / 501.5Syn Z: 1.83
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePLA2G6-related infantile neuroaxonal dystrophyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6646th %ile
GOF
0.6735th %ile
LOF
0.2774th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic24
VUS110
Likely Benign261
Benign41
Conflicting14
39
Pathogenic
24
Likely Pathogenic
110
VUS
261
Likely Benign
41
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
23
3
13
0
39
Likely Pathogenic
13
9
2
0
24
VUS
1
103
6
0
110
Likely Benign
0
16
109
136
261
Benign
0
0
41
0
41
Conflicting
—14
Total37131171136489

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients