Human Gene Module / Chromosome X / GSPT2

GSPT2G1 to S phase transition 2

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
1 / 5
Rare Variants / Common Variants
7 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
Xp11.22
Associated Disorders
-
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.

SFARI Genomic Platforms
Reports related to GSPT2 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Fine-scale survey of X chromosome copy number variants and indels underlying intellectual disability Whibley AC , et al. (2010) No -
2 Support - Christina Grau et al. (2017) No -
3 Support - Halima Al-Shehhi et al. (2019) No -
4 Support - Ashlesha Gogate et al. (2024) Yes -
5 Primary - Yuda Wei et al. (2026) No ASD, ADHD, epilepsy/seizures
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.186C>A p.Asn62Lys missense_variant Familial Maternal Simplex 41420448 Wangfang Xie et al. ()
c.449G>T p.Trp150Leu missense_variant Familial Maternal Simplex 41420448 Wangfang Xie et al. ()
c.665A>G p.Gln222Arg missense_variant Familial Maternal Simplex 41420448 Wangfang Xie et al. ()
c.1413A>C p.Glu471Asp missense_variant Familial Maternal Simplex 41420448 Wangfang Xie et al. ()
c.1477A>C p.Ile493Leu missense_variant Familial Maternal Simplex 41420448 Wangfang Xie et al. ()
c.1817T>G p.Phe606Cys missense_variant Familial Maternal Simplex 41420448 Wangfang Xie et al. ()
c.584C>T p.Pro195Leu missense_variant Familial Maternal Simplex 39632905 Ashlesha Gogate et al. (2024)
Common Variants  

No common variants reported.

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