GCN1 Activator of EIF2AK4
A key regulator of translational control under amino acid starvation and cellular stress
Gene Information Card
| Symbol | GCN1 |
|---|---|
| Full Name | GCN1 activator of EIF2AK4 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q24.23 |
| NCBI Gene ID | 10985 ncbi.nlm.nih.gov/gene/10985 |
| Ensembl ID | ENSG00000135446 |
| UniProt ID | Q92616 |
| OMIM ID | 603555 |
| HGNC ID | 4198 |
| Aliases | GCN1L1, GCN-1, GCN1-like 1 |
Description
GCN1 (GCN1 activator of EIF2AK4) encodes a protein that functions as an activator of the eIF2α kinase GCN2 (EIF2AK4). Under amino acid starvation, GCN1 binds to uncharged tRNA and directly activates GCN2, leading to phosphorylation of eIF2α and global translational repression while promoting translation of specific stress-responsive mRNAs such as ATF4. GCN1 is also implicated in ribosome quality control and cellular stress adaptation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | GCN1 mutations may alter translational control, promoting tumor growth under nutrient stress | COSMIC database; somatic mutations identified in multiple cancer types |
| Neurodegenerative disorders | Dysregulation of GCN1/GCN2 pathway linked to proteotoxic stress | OMIM #603555; literature review |
| Metabolic stress conditions | Impaired GCN1 function disrupts amino acid sensing and metabolic adaptation | UniProt Q92616; functional studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Brain | 15.2 | Medium |
| Liver | 12.8 | Medium |
| Heart | 10.1 | Medium |
| Lung | 8.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 22.4 | High expression |
| HeLa | 18.7 | High expression |
| K562 | 14.2 | Medium expression |
| A549 | 11.5 | Medium expression |
| MCF7 | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Trp) | Missense | <0.1% | Unknown functional effect; reported in COSMIC |
| c.2567A>G (p.Asn856Ser) | Missense | <0.1% | Unknown functional effect; reported in COSMIC |
| c.3456delC | Frameshift | <0.1% | Predicted loss of function; rare |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations predicted to truncate the protein, impairing GCN2 activation and stress signaling.
Gain of Function (GOF)
Not well characterized; no confirmed gain-of-function mutations reported.
Dominant Negative (DN)
Not described for GCN1.
View complete mutation data：
Gene Ontology (GO)
| • translational initiation | • response to amino acid starvation |
| • protein kinase activator activity | • ribosome binding |
| • cytoplasm | • GCN2 kinase activation |
Pathways
• Amino acid starvation response (GCN2 pathway)
• Integrated stress response
• Ribosome quality control
Protein Summary
The GCN1 protein is a large, multi-domain scaffold that directly binds uncharged tRNA and the GCN2 kinase. It is essential for GCN2 activation under amino acid deprivation, leading to eIF2α phosphorylation and reprogramming of translation. GCN1 also participates in ribosome-associated quality control and is conserved from yeast to humans.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GCN1 Knockout HEK293 Cell Line | EDJ-KQ3286 | Human | 10985 | Details Get a Quote |
| GCN1 Knockout A-549 Cell Line | EDJ-KQ24858 | Human | 10985 | Details Get a Quote |
| GCN1 Knockout HCT 116 Cell Line | EDJ-KQ24859 | Human | 10985 | Details Get a Quote |
| GCN1 Knockout HeLa Cell Line | EDJ-KQ24860 | Human | 10985 | Details Get a Quote |
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