Relevance to Autism

Wei et al., 2025 described six individuals from six unrelated Chinese families carrying hemizygous missense variants in the GSPT2 gene presenting with severe intellectual disability/learning disability (5/5), developmental delay with severely delayed speech development (5/5), autism spectrum disorder (3/5), ADHD (3/5), seizures (3/5), and brain malformations (3/5); functional assessment of these variants by Western blot analysis of GSPT2-deficient H4 neuroglioma cells transfected with wild-type or mutant HA-GSPT2 demonstrated either reduced or increased protein expression compared to wild-type. Furthermore, Wei et al., 2025 found that GSPT2-deficient H4 cells displayed a slower growth rate and downregulation of cell proliferation and neurodevelopmental markers compared to wild-type cells. A maternally-inherited hemizygous missense variant in GSPT2 was previously identified in a male ASD proband from a simplex family of Middle Eastern ancestry (Gogate et al., 2024), while copy number variation affecting the GSPT2 gene has been previously reported in individuals presenting with syndromic and non-syndromic intellectual disability (Whibley et al., 2010; Grau et al., 2017; Al-Shehhi et al., 2019).

Molecular Function

This gene encodes a GTPase that belongs to the GTP-binding elongation factor family. The encoded protein is a polypeptide release factor that complexes with eukaryotic peptide chain release factor 1 to mediate translation termination. This protein may also be involved in mRNA stability.

External Links

References