GSPT1 (G1 to S Phase Transition 1): A Key Translation Termination Factor and Emerging Cancer Biomarker
Comprehensive genomic, expression, and mutation analysis of GSPT1, encoding eukaryotic peptide chain release factor GTP-binding subunit eRF3a, with implications in cancer and neurodevelopment.
Gene Information Card
| Symbol | GSPT1 |
|---|---|
| Full Name | G1 to S phase transition 1 |
| Gene Type | protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 2935 ncbi.nlm.nih.gov/gene/2935 |
| Ensembl ID | ENSG00000166226 |
| UniProt ID | P15170 |
| OMIM ID | 139260 |
| HGNC ID | 4621 |
| Aliases | eRF3a, GST1, ETF3A, ERF3A, MGC126258, MGC126260 |
Description
GSPT1 encodes eukaryotic peptide chain release factor GTP-binding subunit eRF3a, a GTPase essential for translation termination. It forms a complex with eRF1 and promotes stop codon recognition and peptide release. GSPT1 is involved in cell cycle progression, apoptosis, and cytoskeletal organization. Mutations and altered expression are linked to various cancers and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Overexpression of GSPT1 promotes tumor cell proliferation and metastasis; knockdown reduces cell viability. | COSMIC; multiple studies (e.g., PMID: 31211834) |
| Breast cancer | High GSPT1 expression correlates with poor prognosis; regulates epithelial-mesenchymal transition. | COSMIC; PMID: 31578321 |
| Lung cancer | GSPT1 amplification and overexpression contribute to oncogenic transformation. | COSMIC; PMID: 30120242 |
| Neurodevelopmental disorder with intellectual disability and seizures | Heterozygous missense variants in GSPT1 impair translation termination, leading to neurodevelopmental phenotypes. | ClinVar; PMID: 32860008 |
| Gastric cancer | GSPT1 upregulation associated with tumor progression and chemoresistance. | COSMIC; PMID: 30565922 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 45.2 | High |
| Brain | 28.7 | Medium |
| Lung | 20.3 | Medium |
| Liver | 15.8 | Low |
| Kidney | 12.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 35.6 | Cervical cancer cell line; high expression |
| A549 | 22.1 | Lung cancer cell line; moderate expression |
| MCF7 | 18.9 | Breast cancer cell line; moderate expression |
| HCT116 | 30.4 | Colorectal cancer cell line; high expression |
| HEK293 | 25.3 | Embryonic kidney; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg306Cys | Missense | Rare (ClinVar) | Impairs GTPase activity and translation termination; associated with neurodevelopmental disorder |
| p.Gly338Asp | Missense | Rare (ClinVar) | Likely pathogenic; disrupts eRF1 binding |
| p.Leu351Phe | Missense | Somatic (COSMIC) | Potential gain-of-function; observed in colorectal cancer |
| p.Gln577* | Nonsense | Somatic (COSMIC) | Loss-of-function; may lead to haploinsufficiency in tumors |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate eRF3a, reducing translation termination efficiency and leading to ribosomal readthrough; observed in some cancers and neurodevelopmental cases.
Gain of Function (GOF)
Missense mutations that enhance GTPase activity or stabilize the protein, promoting oncogenic signaling; rare but reported in solid tumors.
Dominant Negative (DN)
Missense mutations that disrupt eRF3a-eRF1 interaction, interfering with normal termination complex assembly; implicated in neurodevelopmental disorders.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activity | • translation release factor activity |
| • protein binding | • GTP binding |
| • cytoplasm | • ribosome |
| • translation termination | • regulation of translational termination |
| • cell cycle | • apoptotic process |
Pathways
• Eukaryotic translation termination
• nonsense-mediated decay
• regulation of mRNA stability
• p53 signaling pathway (via interaction with MDM2)
• Wnt signaling pathway (modulation of beta-catenin)
Protein Summary
GSPT1 encodes eRF3a, a 637-amino acid protein with an N-terminal prion-like domain and a C-terminal GTPase domain. It forms a complex with eRF1 to catalyze stop codon recognition and peptide release. eRF3a also interacts with PABP, promoting mRNA circularization and efficient translation. Post-translational modifications include phosphorylation and ubiquitination, regulating its stability. The protein is predominantly cytoplasmic but can localize to the nucleus under stress. Its expression is cell-cycle dependent, peaking at G1/S transition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GSPT1 Knockout HAP1 Cell Line | EDJ-KQ78118 | Human | 2935 | Details Get a Quote |
