EIF2S3 Gene - Eukaryotic Translation Initiation Factor 2 Subunit Gamma
Essential component of the eIF2 complex involved in protein synthesis initiation
Gene Information Card
| Symbol | EIF2S3 |
|---|---|
| Full Name | Eukaryotic Translation Initiation Factor 2 Subunit Gamma |
| Gene Type | Protein coding |
| Chromosomal Location | Xp22.11 |
| NCBI Gene ID | 1968 ncbi.nlm.nih.gov/gene/1968 |
| Ensembl ID | ENSG00000130711 |
| UniProt ID | P41091 |
| OMIM ID | 300161 |
| HGNC ID | 3267 |
| Aliases | EIF2G, eIF-2gamma, eIF2gamma |
Description
EIF2S3 encodes the gamma subunit of eukaryotic translation initiation factor 2 (eIF2), a heterotrimeric complex essential for the initiation of protein synthesis. The gamma subunit binds GTP and Met-tRNAi, facilitating the delivery of the initiator methionyl-tRNA to the 40S ribosomal subunit. Mutations in EIF2S3 cause MEHMO syndrome (Mental retardation, Epileptic seizures, Hypogenitalism, Microcephaly, Obesity) and X-linked intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| MEHMO syndrome | Loss-of-function mutations impair eIF2 complex assembly and translation initiation, leading to multisystem developmental defects | OMIM #300148 |
| X-linked intellectual disability 96 | Missense variants disrupt GTP binding or subunit interaction, reducing global protein synthesis in neurons | OMIM #300161 |
| Microcephaly | Defective translation reduces neural progenitor cell proliferation during brain development | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | High |
| Testis | 12.8 | High |
| Pancreas | 10.5 | Medium |
| Liver | 8.3 | Medium |
| Heart | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | High expression |
| HeLa | 14.7 | High expression |
| K562 | 11.2 | Medium expression |
| HepG2 | 9.8 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.179A>G (p.Asn60Ser) | Missense | Rare | Impaired GTP binding; associated with MEHMO syndrome |
| c.430C>T (p.Arg144Trp) | Missense | Rare | Reduced eIF2 complex stability; intellectual disability |
| c.832G>A (p.Glu278Lys) | Missense | Rare | Dominant-negative effect on translation initiation |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., Asn60Ser) reduce GTP binding and eIF2 complex formation, leading to global translation defects.
Gain of Function (GOF)
Not reported for EIF2S3.
Dominant Negative (DN)
Glu278Lys variant disrupts subunit interaction, impairing wild-type eIF2 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Eukaryotic Translation Initiation (Reactome R-HSA-72613)
• GTP hydrolysis and joining of the 60S ribosomal subunit (Reactome R-HSA-72706)
• Translation (KEGG hsa03010)
Protein Summary
EIF2S3 encodes the gamma subunit (55 kDa) of the eukaryotic initiation factor 2 (eIF2) complex. The protein contains a GTP-binding domain that is critical for binding Met-tRNAi and delivering it to the 40S ribosomal subunit. It interacts with the alpha and beta subunits of eIF2. Mutations in this gene cause MEHMO syndrome and X-linked intellectual disability due to impaired translation initiation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EIF2S3B Knockout HEK293 Cell Line | EDJ-KQ11793 | Human | 255308 | Details Get a Quote |
| EIF2S3B Knockout A-549 Cell Line | EDJ-KQ40201 | Human | 255308 | Details Get a Quote |
| EIF2S3B Knockout HCT 116 Cell Line | EDJ-KQ40202 | Human | 255308 | Details Get a Quote |
| EIF2S3B Knockout HeLa Cell Line | EDJ-KQ40203 | Human | 255308 | Details Get a Quote |
