Paternally expressed gene 10 (PEG10)

Paternally expressed gene 10 (PEG10) is a retrotransposon-derived imprinted gene that plays a critical role in mammalian development and disease (UniProt, 2024; NIH, 2025). It is evolutionarily derived from the Ty3/Gypsy family of retrotransposons and utilizes a unique -1 ribosomal frameshift mechanism to produce two distinct protein isoforms: a gag-like protein (RF1) and a gag-pol-like fusion protein (RF1/2) with aspartic protease activity (PLoS One, 2010; Wikipedia, 2024). Biologically, PEG10 is essential for placental development and trophoblast differentiation, and it has been shown to self-assemble into virion-like capsids that facilitate the intercellular transfer of its own mRNA (Frontiers, 2023; GeneCards, 2024). In the context of oncology, PEG10 is frequently overexpressed in various malignancies, including hepatocellular carcinoma and breast cancer, where it promotes cell proliferation, inhibits apoptosis, and contributes to drug resistance, particularly against CDK4/6 inhibitors (NIH, 2018; NIH, 2023). It also has emerging roles in neurodegenerative disorders like Amyotrophic Lateral Sclerosis (ALS) and Angelman syndrome due to its interaction with protein degradation pathways (NIH, 2025). While no approved drugs currently target PEG10, it is being actively investigated as a therapeutic target using antisense oligonucleotides, siRNAs, and small molecules designed to inhibit its ribosomal frameshifting or expression (NIH, 2023; Spandidos, 2025).

Other names

Retrotransposon-derived protein PEG10Embryonal carcinoma differentiation-regulated proteinEDRHB-1Myelin expression factor 3-like protein 1MEF3LMammalian retrotransposon-derived protein 2Mar2Mart2Retrotransposon gag domain-containing protein 3RGAG3Retrotransposon-like protein 2RTL2Sushi-ichi retrotransposon homolog 1SIRH1KIAA1051

Inhibition of PEG10 expression via RNA interference or antisense technology, or inhibition of -1 ribosomal frameshifting to prevent the production of the oncogenic RF1/2 fusion protein (NIH, 2023; Spandidos, 2025).