PNPLA2

Chr 11p15.5

patatin like domain 2, triacylglycerol lipase

Aliases:: desnutrin, TTS-2.2, ATGL, FP17548, iPLA2zeta
MANE:: ENST00000336615.9

OMIM: 609059 ↗NCBI: 57104 ↗Ensembl ↗

Annotations refreshed 11 hours ago.

Predicted protein structure

AlphaFold predicted structure

PNPLA2 · Q96AD5

v62025-08-01

Predicted Aligned Error matrix for PNPLA2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

72.5/ 100

Confident

504 residues

Confidence breakdown

Very high(≥ 90)37%
Confident(70–90)27%
Low(50–70)8%
Very low(< 50)28%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism
BIALLELIC, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies
BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders
BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy
BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis
BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies

Disease associations (Open Targets)

neutral lipid storage myopathy
0.80
hereditary disease
0.46
Abnormality of the skeletal system
0.40
Fuchs endothelial corneal dystrophy
0.34
Abnormality of the musculature
0.33
breast cancer
0.32
keratoconus
0.23
familial dilated cardiomyopathy
0.19
corneal dystrophy
0.15
Fuchs' endothelial dystrophy
0.14

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Patatin-like phospholipase domain-containing protein 2

Catalyzes the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets (PubMed:15364929, PubMed:15550674, PubMed:16150821, PubMed:16239926, PubMed:17603008, PubMed:34903883). Exhibits a strong preference for the hydrolysis of long-chain fatty acid esters at the sn-2 position of the glycerol backbone and acts coordinately with LIPE/HLS and DGAT2 within the lipolytic cascade (By similarity). Also possesses acylglycerol transacylase and phospholipase A2 activities (PubMed:15364929, PubMed:17032652, PubMed:17603008). Transfers fatty acid from triglyceride to retinol, hydrolyzes retinylesters, and generates 1,3-diacylglycerol from triglycerides (PubMed:17603008). Regulates adiposome size and may be involved in the degradation of adiposomes (PubMed:16239926). Catalyzes the formation of an ester bond between hydroxy fatty acids and fatty acids derived from triglycerides or diglycerides to generate fatty acid esters of hydroxy fatty acids (FAHFAs) in adipocytes (PubMed:35676490). Acts antagonistically with LDAH in regulation of cellular lipid stores (PubMed:28578400). Inhibits LDAH-stimulated lipid droplet fusion (PubMed:28578400). May play an important role in energy homeostasis (By similarity). May play a role in the response of the organism to starvation, enhancing hydrolysis of triglycerides and providing free fatty acids to other tissues to be oxidized in situations of energy depletion (By similarity)