EIF2S1
protein-codingeukaryotic translation initiation factor 2 subunit alpha
Gene summary
The translation initiation factor EIF2 catalyzes the first regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, EIF2, and GTP. EIF2 is composed of 3 nonidentical subunits, the 36-kD EIF2-alpha subunit (EIF2S1), the 38-kD EIF2-beta subunit (EIF2S2; MIM 603908), and the 52-kD EIF2-gamma subunit (EIF2S3; MIM 300161). The rate of formation of the ternary complex is modulated by the phosphorylation state of EIF2-alpha (Ernst et al., 1987 [PubMed 2948954]).[supplied by OMIM, Feb 2010]
- EIF2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~26.2 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 EIF2S1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004094.5. 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 | 1 | 1 | ||||
| missense | 16 | 1 | 17 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 17 | 1 | 1 | 19 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004085.1 | 7 | MANE Select | |
| Ensembl | ENSP00000256383.4 | 7 | MANE Select | |
| Ensembl | ENSP00000425299.1 | 7 | Standard | |
| Ensembl | ENSP00000452034.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
- Influenza A - Homo sapiens (human)
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- Autophagy - animal - Homo sapiens (human)
- RNA transport - Homo sapiens (human)
Biological Process
- translational initiation
- aging
- negative regulation of translational initiation in response to stress
- stress granule assembly
- cellular response to amino acid starvation
Molecular Function
- RNA binding
- translation initiation factor activity
- protein binding
- ribosome binding
Cellular Component
- nucleus
- cytosol
- polysome
- eukaryotic translation initiation factor 2 complex
- eukaryotic translation initiation factor 2B complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000256383
- Coding exons
- 7
- Length
- 26520
- Individuals with no LoFs
- 123973
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 123974
- p
- 0.00000403
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.86 | 67 | 173 | 0.388 | 0.00000873 | 2081 |
| Missense (PolyPhen) | 10 | 68.361 | 0.14628 | 778 | ||
| Synonymous | 1.47 | 43 | 57.2 | 0.752 | 0.00000268 | 574 |
| Loss of Function | 3.39 | 1 | 15.3 | 0.0654 | 8.86e-7 | 193 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2- GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B.;
Recessive Scores
- pRec
- 0.493
Intolerance Scores
- LoFtool
- 0.212
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 38.28
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.990
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |