PNPLA2
Chr 11ARpatatin like domain 2, triacylglycerol lipase
Also known as: 1110001C14Rik, ATGL, FP17548, PEDF-R, TTS-2.2, TTS2, iPLA2zeta
The protein catalyzes the initial step in triglyceride hydrolysis in lipid droplets and plays a key role in energy homeostasis by breaking down stored fats. Mutations cause neutral lipid storage disease with myopathy, an autosomal recessive disorder characterized by abnormal lipid accumulation affecting muscle tissue. The gene is not highly constrained against loss-of-function variants.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
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
539 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 23 | 3 | 18 | 0 | 44 |
Likely Pathogenic | 8 | 1 | 0 | 0 | 9 |
VUS | 7 | 198 | 19 | 1 | 225 |
Likely Benign | 0 | 4 | 92 | 128 | 224 |
Benign | 0 | 2 | 7 | 4 | 13 |
Conflicting | — | 9 | |||
| Total | 38 | 208 | 136 | 133 | 524 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PNPLA2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools