PNPLA8

Chr 7q31.1

patatin like domain 8, phospholipase A2

Aliases:: IPLA2G, IPLA2-2, iPLA2gamma
MANE:: ENST00000257694.13

OMIM: 612123 ↗NCBI: 50640 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

PNPLA8 · Q9NP80

v62025-08-01

Predicted Aligned Error matrix for PNPLA8 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

66.9/ 100

Low

782 residues

Confidence breakdown

Very high(≥ 90)40%
Confident(70–90)12%
Low(50–70)7%
Very low(< 50)41%

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
Early onset or syndromic epilepsy
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism
BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders
BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes
BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

mitochondrial myopathy-lactic acidosis-deafness syndrome
0.73
inborn mitochondrial metabolism disorder
0.37
mitochondrial disease
0.37
hereditary disease
0.34
Abnormality of the musculature
0.27
musculoskeletal system disorder
0.26
complex neurodevelopmental disorder
0.12
myopia
0.10
insomnia
0.09
breast carcinoma
0.07

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

Protein function (UniProt)

Calcium-independent phospholipase A2-gamma

Calcium-independent and membrane-bound phospholipase, that catalyzes the esterolytic cleavage of fatty acids from glycerophospholipids to yield free fatty acids and lysophospholipids, hence regulating membrane physical properties and the release of lipid second messengers and growth factors (PubMed:10744668, PubMed:10833412, PubMed:15695510, PubMed:15908428, PubMed:17213206, PubMed:18171998, PubMed:28442572). Hydrolyzes phosphatidylethanolamine, phosphatidylcholine and probably phosphatidylinositol with a possible preference for the former (PubMed:15695510). Also has a broad substrate specificity in terms of fatty acid moieties, hydrolyzing saturated and mono-unsaturated fatty acids at nearly equal rates from either the sn-1 or sn-2 position in diacyl phosphatidylcholine (PubMed:10744668, PubMed:10833412, PubMed:15695510, PubMed:15908428). However, has a weak activity toward polyunsaturated fatty acids at the sn-2 position, and thereby favors the production of 2-arachidonoyl lysophosphatidylcholine, a key branch point metabolite in eicosanoid signaling (PubMed:15908428). On the other hand, can produce arachidonic acid from the sn-1 position of diacyl phospholipid and from the sn-2 position of arachidonate-containing plasmalogen substrates (PubMed:15908428). Therefore, plays an important role in the mobilization of arachidonic acid in response to cellular stimuli and the generation of lipid second messengers (PubMed:15695510, PubMed:15908428). Can also hydrolyze lysophosphatidylcholine (PubMed:15695510). In the mitochondrial compartment, catalyzes the hydrolysis and release of oxidized aliphatic chains from cardiolipin and integrates mitochondrial bioenergetics and signaling. It is essential for maintaining efficient bioenergetic mitochondrial function through tailoring mitochondrial membrane lipid metabolism and composition (PubMed:28442572)