EIF4G2
protein-codingeukaryotic translation initiation factor 4 gamma 2, the group of MIF4G domain containing proteins|Small nucleolar RNA protein coding host genes
Gene summary
Translation initiation is mediated by specific recognition of the cap structure by eukaryotic translation initiation factor 4F (eIF4F), which is a cap binding protein complex that consists of three subunits: eIF4A, eIF4E and eIF4G. The protein encoded by this gene shares similarity with the C-terminal region of eIF4G that contains the binding sites for eIF4A and eIF3; eIF4G, in addition, contains a binding site for eIF4E at the N-terminus. Unlike eIF4G, which supports cap-dependent and independent translation, this gene product functions as a general repressor of translation by forming translationally inactive complexes. In vitro and in vivo studies indicate that translation of this mRNA initiates exclusively at a non-AUG (GUG) codon. Alternatively spliced transcript variants encoding different isoforms of this gene have been described. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.9 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 EIF4G2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001418.4. 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 | 3 | 2 | 1 | 6 | ||
| missense | 73 | 1 | 74 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 82 | 3 | 1 | 86 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001409.3 | 21 | MANE Select | |
| Ensembl | ENSP00000340281.6 | 21 | MANE Select | |
| RefSeq | NP_001036024.3 | 20 | Standard | |
| RefSeq | NP_001166176.1 | 21 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Viral myocarditis - Homo sapiens (human)
- RNA transport - Homo sapiens (human)
- Exercise-induced Circadian Regulation
- internal ribosome entry pathway
- Cytokine Signaling in Immune system
Biological Process
- translational initiation
- regulation of translational initiation
- cell cycle arrest
- cell death
- negative regulation of autophagy
Molecular Function
- RNA binding
- mRNA binding
- translation initiation factor activity
- protein binding
- translation factor activity, RNA binding
Cellular Component
- cytosol
- cell-cell adherens junction
- membrane
- eukaryotic translation initiation factor 4F complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000526148
- Coding exons
- 21
- Length
- 12061
- Individuals with no LoFs
- 125721
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125724
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.98 | 304 | 490 | 0.621 | 0.0000254 | 6011 |
| Missense (PolyPhen) | 80 | 212.32 | 0.37679 | 2727 | ||
| Synonymous | -0.276 | 176 | 171 | 1.03 | 0.00000917 | 1668 |
| Loss of Function | 6.79 | 1 | 55.6 | 0.0180 | 0.00000330 | 608 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Appears to play a role in the switch from cap-dependent to IRES-mediated translation during mitosis, apoptosis and viral infection. Cleaved by some caspases and viral proteases. {ECO:0000269|PubMed:11511540, ECO:0000269|PubMed:11943866, ECO:0000269|PubMed:9032289, ECO:0000269|PubMed:9049310}.;
Recessive Scores
- pRec
- 0.153
Intolerance Scores
- RVIS EVS
- -1.09
- RVIS percentile EVS
- 7.11
Essentials
- Essential (CRISPR)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.967
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |