Retrotransposon Gag-like protein 8A (RTL8A)

Retrotransposon Gag-like protein 8A (RTL8A) is a eutherian mammalian-specific protein derived from an endogenous retroviral Gag gene. It forms part of a gene cluster on the X chromosome, with paralogs RTL8B and RTL8C, and displays high conservation across mammals, highlighting its functional importance. RTL8A is expressed predominantly in the brain—including the prefrontal cortex and hypothalamus—and localizes to both the nucleus and cytoplasm of neurons, likely through an N-terminal nuclear localization signal. Studies in mice show that loss of RTL8A (and its closely related RTL8B) leads to late-onset obesity, reduced social behavior, and apathy-like traits, mirroring features of human neurodevelopmental disorders such as Prader–Willi syndrome. The behavioral and physiological phenotypes appear to involve altered GABAergic neurotransmission, particularly through reduced expression of GABRB2 (GABA type A receptor β2 subunit) in the cerebral cortex. Human data further suggest RTL8A involvement in Angelman syndrome and ALS: its levels are altered in neurons derived from patient iPSCs. While it is not a classical therapeutic target (like a receptor or enzyme), RTL8A represents an emergent area of interest for understanding the molecular underpinnings of neurodevelopmental and neuropsychiatric disorders

Other names

CXX1BFAM127BMAR8ADKFZP564B147CXX1bSIRH6Sushi-Ichi retrotransposon homolog 6family with sequence similarity 127 member Bmammalian retrotransposon-derived protein 8Aprotein FAM127B