EIF4G3 (eIF4G3) Gene: Eukaryotic Translation Initiation Factor 4 Gamma 3
A key scaffold protein in cap-dependent translation initiation, implicated in neurological disorders and cancer.
Gene Information Card
| Symbol | EIF4G3 |
|---|---|
| Full Name | Eukaryotic Translation Initiation Factor 4 Gamma 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p36.12 |
| NCBI Gene ID | 8672 ncbi.nlm.nih.gov/gene/8672 |
| Ensembl ID | ENSG00000075151 |
| UniProt ID | O43432 |
| OMIM ID | 603929 |
| HGNC ID | 3298 |
| Aliases | eIF4GII, eIF-4G 3, eIF4G 3, DKFZp686B1020 |
Description
EIF4G3 encodes a member of the eukaryotic translation initiation factor 4G (eIF4G) family. This protein functions as a scaffold that binds eIF4E (cap-binding protein) and eIF4A (RNA helicase) to form the eIF4F complex, which is essential for cap-dependent translation initiation. EIF4G3 is involved in recruiting mRNA to the ribosome and plays a role in cellular growth, proliferation, and stress responses. Alternative splicing generates multiple transcript variants.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual Disability, Autosomal Dominant 64 (MRD64) | Heterozygous missense mutations in EIF4G3 impair cap-dependent translation initiation, leading to reduced global protein synthesis and neuronal dysfunction. | OMIM #618718; PMID: 31474318 |
| Colorectal Cancer | Overexpression and amplification of EIF4G3 contribute to enhanced translation of oncogenic mRNAs, promoting tumorigenesis. | COSMIC; PMID: 23542345 |
| Breast Cancer | EIF4G3 upregulation correlates with poor prognosis and increased eIF4F complex activity, driving translation of pro-survival factors. | PMID: 25605274 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 9.8 | Medium |
| Brain (cortex) | 8.5 | Medium |
| Heart | 7.2 | Medium |
| Liver | 6.1 | Low |
| Testis | 12.3 | High |
| Lung | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 (embryonic kidney) | 14.2 | High expression |
| HeLa (cervical carcinoma) | 11.5 | High expression |
| K562 (leukemia) | 8.9 | Medium expression |
| HepG2 (hepatocellular carcinoma) | 6.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1946G>A (p.Arg649Gln) | Missense | Rare | Impaired eIF4E binding; associated with MRD64 |
| c.2152C>T (p.Arg718Trp) | Missense | Rare | Reduced translation initiation efficiency; associated with MRD64 |
| Amplification | Copy number gain | Frequent in colorectal cancer | Increased EIF4G3 expression; promotes oncogenic translation |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg649Gln, p.Arg718Trp) reduce eIF4E binding and cap-dependent translation, leading to haploinsufficiency in neurons.
Gain of Function (GOF)
Gene amplification and overexpression in cancers enhance eIF4F complex assembly, increasing translation of oncogenic mRNAs.
Dominant Negative (DN)
Not reported for EIF4G3.
View complete mutation data：
Gene Ontology (GO)
| • translation initiation factor activity (GO:0003743) | • regulation of translation (GO:0006417) |
| • eIF4F complex (GO:0002199) | • RNA binding (GO:0003723) |
| • protein binding (GO:0005515) |
Pathways
• hsa04141 - Protein processing in endoplasmic reticulum
• hsa03013 - RNA transport
• hsa05200 - Pathways in cancer
• hsa04150 - mTOR signaling pathway
Protein Summary
The EIF4G3 protein (eIF4GII) is a 1585-amino-acid scaffold that contains binding sites for eIF4E, eIF4A, eIF3, and poly(A)-binding protein (PABP). It is a core component of the eIF4F complex, which mediates the recruitment of capped mRNAs to the 43S pre-initiation complex. The protein is widely expressed, with highest levels in testis and brain. Post-translational modifications include phosphorylation by mTOR and other kinases, regulating its activity in response to growth signals and stress.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EIF4G3 Knockout HEK293 Cell Line | EDJ-KQ6321 | Human | 8672 | Details Get a Quote |
| EIF4G3 Knockout A-549 Cell Line | EDJ-KQ30250 | Human | 8672 | Details Get a Quote |
| EIF4G3 Knockout HCT 116 Cell Line | EDJ-KQ30251 | Human | 8672 | Details Get a Quote |
| EIF4G3 Knockout HeLa Cell Line | EDJ-KQ30252 | Human | 8672 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
