EIF2S2
protein-codingeukaryotic translation initiation factor 2 subunit beta, the group of Protein phosphatase 1 regulatory subunits
Gene summary
Eukaryotic translation initiation factor 2 (EIF-2) functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA and binding to a 40S ribosomal subunit. EIF-2 is composed of three subunits, alpha, beta, and gamma, with the protein encoded by this gene representing the beta subunit. The beta subunit catalyzes the exchange of GDP for GTP, which recycles the EIF-2 complex for another round of initiation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
- EIF2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~23.9 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 EIF2S2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003908.5. 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 | 2 | 1 | 4 | ||
| missense | 18 | 1 | 19 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 21 | 3 | 1 | 25 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003899.2 | 9 | MANE Select | |
| Ensembl | ENSP00000364119.2 | 9 | MANE Select | |
| RefSeq | NP_001303292.1 | 9 | Standard | |
| RefSeq | NP_001303293.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- RNA transport - Homo sapiens (human)
- Translation Factors
- Brain-Derived Neurotrophic Factor (BDNF) signaling pathway
- double stranded rna induced gene expression
- skeletal muscle hypertrophy is regulated via akt-mtor pathway
Biological Process
- in utero embryonic development
- male germ cell proliferation
- translational initiation
- male gonad development
- transmembrane transport
Molecular Function
- RNA binding
- translation initiation factor activity
- protein binding
- translation factor activity, RNA binding
- metal ion binding
Cellular Component
- nucleus
- cytoplasm
- cytosol
- eukaryotic translation initiation factor 2 complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374980
- Coding exons
- 9
- Length
- 24035
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125741
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.90 | 61 | 166 | 0.368 | 0.00000819 | 2234 |
| Missense (PolyPhen) | 8 | 47.762 | 0.1675 | 733 | ||
| Synonymous | 0.225 | 55 | 57.2 | 0.962 | 0.00000298 | 562 |
| Loss of Function | 3.55 | 2 | 18.4 | 0.108 | 0.00000111 | 233 |
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 | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: eIF-2 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 preinitiation 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
- 0.190
Intolerance Scores
- LoFtool
- 0.428
- RVIS EVS
- 0.1
- RVIS percentile EVS
- 61.28
Essentials
- Essential (CRISPR)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.965
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |