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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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GPAT2
glycerol-3-phosphate acyltransferase 2, mitochondrial
Chromosome 2 Β· 2q11.2
NCBI Gene: 150763Ensembl: ENSG00000186281.13HGNC: HGNC:27168UniProt: B4DNZ9
11PubMed Papers
20Diseases
0Drugs
3Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mitochondrionglycerol-3-phosphate O-acyltransferase activity1-acylglycerol-3-phosphate O-acyltransferase activityglycerophospholipid metabolic processmale infertilityazoospermiapartial chromosome Y deletionspinocerebellar ataxia type 32
✦AI Summary

GPAT2 is a mitochondrial outer membrane enzyme catalyzing the first rate-limiting step in glycerolipid synthesis by transferring acyl groups from acyl-CoA to glycerol-3-phosphate, producing lysophosphatidic acid and subsequently phosphatidic acid 1. The enzyme preferentially utilizes arachidonoyl-CoA as substrate and is uniquely required for piRNA biogenesis through a mechanism independent of its acyltransferase activity 2. GPAT2 expression is restricted to male germ cells and cancer cells under physiological conditions 3. In spermatogenesis, GPAT2 is essential for normal germ cell development; its absence triggers germ cell apoptosis and arrests development at the pachytene stage 3. Biallelic GPAT2 variants cause human male infertility through impaired piRNA biogenesis, leading to transposon de-repression and germ cell loss 2. In breast cancer, GPAT2 overexpression promotes tumor progression by preventing arachidonic acid-induced apoptosis and modulating membrane properties including cell roughness and permeability 45. GPAT2 may contribute to metabolic disorders including hepatic steatosis and insulin resistance 6. The protein contains two transmembrane segments with enzymatically active motifs facing the cytosol 7.

Sources cited
1
GPAT2 variants cause human male infertility through impaired piRNA biogenesis and transposon de-silencing
PMID: 39122675
2
GPAT2 is a mitochondrial enzyme catalyzing the rate-limiting step in glycerolipid and TAG synthesis
PMID: 30813330
3
GPAT2 is essential for spermatogenesis; its silencing causes germ cell apoptosis and developmental arrest
PMID: 28729426
4
GPAT2 has two transmembrane segments with enzymatically active motifs facing the cytosol
PMID: 22285183
5
GPAT2 overexpression in breast cancer prevents arachidonic acid-induced apoptosis
PMID: 39605002
6
GPAT2 expression alters membrane properties and arachidonic acid content in glycerolipids
PMID: 29211789
7
GPAT2 plays a critical role in metabolic syndrome development including hepatic steatosis and insulin resistance
PMID: 36059117
Disease Associationsβ“˜20
male infertilityOpen Targets
0.38Weak
azoospermiaOpen Targets
0.09Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
spinocerebellar ataxia type 32Open Targets
0.06Suggestive
spermatogenic failure 50Open Targets
0.06Suggestive
spermatogenic failure 57Open Targets
0.06Suggestive
spermatogenic failure 25Open Targets
0.06Suggestive
isochromosomy YpOpen Targets
0.06Suggestive
spermatogenic failure, X-linked, 2Open Targets
0.06Suggestive
spermatogenic failure 71Open Targets
0.06Suggestive
congenital bilateral absence of vas deferensOpen Targets
0.06Suggestive
spermatogenic failure 63Open Targets
0.06Suggestive
spermatogenic failure 12Open Targets
0.06Suggestive
spermatogenic failure 61Open Targets
0.06Suggestive
spermatogenic failure 62Open Targets
0.06Suggestive
spermatogenic failure 88Open Targets
0.06Suggestive
spermatogenic failure 48Open Targets
0.06Suggestive
spermatogenic failure 59Open Targets
0.06Suggestive
spermatogenic failure 73Open Targets
0.06Suggestive
spermatogenic failure 74Open Targets
0.06Suggestive
Pathogenic Variants3
NM_001321527.2(GPAT2):c.1156-1G>ALikely pathogenic
Male infertility
β˜…β˜†β˜†β˜†2023
NM_001321527.2(GPAT2):c.1954C>T (p.Arg652Ter)Likely pathogenic
Male infertility
β˜…β˜†β˜†β˜†2023β†’ Residue 652
NM_001321527.2(GPAT2):c.1879C>T (p.Arg627Trp)Likely pathogenic
Male infertility
β˜…β˜†β˜†β˜†2023β†’ Residue 627
View on ClinVar β†—
Related Genes
GK2Protein interaction98%GPD1Protein interaction98%AGPAT1Protein interaction98%GPD1LProtein interaction98%AGPAT5Protein interaction98%AGKProtein interaction98%
Tissue Expression6 tissues
Heart
100%
Ovary
99%
Lung
73%
Liver
57%
Brain
39%
Bone Marrow
25%
Gene Interaction Network
Click a node to explore
GPAT2GK2GPD1AGPAT1GPD1LAGPAT5AGK
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q6NUI2
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.07LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.85 [0.68–1.07]
RankingsWhere GPAT2 stands among ~20K protein-coding genes
  • #16,770of 20,598
    Most Researched11
  • #4,168of 5,498
    Most Pathogenic Variants3
  • #10,797of 17,882
    Most Constrained (LOEUF)1.07
Genes detectedGPAT2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Inherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility.
PMID: 39122675
Nat Commun Β· 2024
1.00
2
Transcriptional Regulation of Acyl-CoA:Glycerol-
PMID: 30813330
Int J Mol Sci Β· 2019
0.90
3
Glycerol-3-phosphate acyltransferase 2 is essential for normal spermatogenesis.
PMID: 28729426
Biochem J Β· 2017
0.80
4
Membrane topology of murine glycerol-3-phosphate acyltransferase 2.
PMID: 22285183
Biochem Biophys Res Commun Β· 2012
0.70
5
The protumorigenic enzyme GPAT2 inhibits arachidonic acid-triggered apoptosis in breast cancer.
PMID: 39605002
Lipids Health Dis Β· 2024
0.60