GCN1
protein-codingGCN1 activator of EIF2AK4, the group of MicroRNA protein coding host genes|TOG domain containing
Gene summary
Enables molecular adaptor activity and stalled ribosome sensor activity. Involved in protein-RNA covalent cross-linking repair. Located in cytosol. Is active in cytosolic ribosome. [provided by Alliance of Genome Resources, Jun 2026]
- GCN1L1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~67.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GCN1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006836.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 12 | 8 | 5 | 25 | ||
| missense | 329 | 7 | 1 | 337 | ||
| nonsense | 5 | 5 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 12 | 12 | ||||
| Total | 0 | 0 | 358 | 15 | 6 | 379 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006827.1 | 58 | MANE Select | |
| Ensembl | ENSP00000300648.6 | 58 | MANE Select | |
| Ensembl | ENSP00000561905.1 | 58 | Standard | |
| Ensembl | ENSP00000561905.1 | 58 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- translation
- regulation of translation
- positive regulation of kinase activity
- cellular response to amino acid starvation
- positive regulation of transcription from RNA polymerase II promoter in response to stress
Molecular Function
- RNA binding
- translation factor activity, RNA binding
- protein kinase regulator activity
- protein kinase binding
- ribosome binding
Cellular Component
- cytoplasm
- cytosol
- ribosome
- polysome
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000300648
- Coding exons
- 58
- Length
- 67507
- Individuals with no LoFs
- 124774
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 46
- Defined
- 124820
- p
- 0.000184
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.44 | 1069 | 1.56e+3 | 0.684 | 0.0000960 | 17230 |
| Missense (PolyPhen) | 318 | 581.67 | 0.5467 | 6292 | ||
| Synonymous | -0.503 | 693 | 676 | 1.02 | 0.0000443 | 5612 |
| Loss of Function | 9.03 | 18 | 128 | 0.140 | 0.00000667 | 1481 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00039 | 0.00032 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00028 | 0.00023 | rare |
| European (Non-Finnish) | 0.00024 | 0.00024 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a positive activator of the EIF2AK4/GCN2 protein kinase activity in response to amino acid starvation. Forms a complex with EIF2AK4/GCN2 on translating ribosomes; during this process, GCN1 seems to act as a chaperone to facilitate delivery of uncharged tRNAs that enter the A site of ribosomes to the tRNA- binding domain of EIF2AK4/GCN2, and hence stimulating EIF2AK4/GCN2 kinase activity. Participates in the repression of global protein synthesis and in gene-specific mRNA translation activation, such as the transcriptional activator ATF4, by promoting the EIF2AK4/GCN2-mediated phosphorylation of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52', and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. {ECO:0000250|UniProtKB:E9PVA8, ECO:0000250|UniProtKB:P33892}.;
Recessive Scores
- pRec
- 0.391
Intolerance Scores
- RVIS EVS
- -3.77
- RVIS percentile EVS
- 0.24
Essentials
- Essential (gene trap)
- H