EIF3G
protein-codingeukaryotic translation initiation factor 3 subunit G, the group of RNA binding motif containing|Eukaryotic translation initiation factor 3
Gene summary
This gene encodes a core subunit of the eukaryotic translation initiation factor 3 (eIF3) complex, which is required for initiation of protein translation. An N-terminal caspase cleavage product of the encoded protein may stimulate degradation of DNA. A mutation in this gene is associated with narcolepsy. [provided by RefSeq, Jul 2016]
- EIF3S4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.9 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 EIF3G variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003755.5. 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 | 2 | 2 | ||||
| missense | 36 | 2 | 38 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 46 | 2 | 0 | 48 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003746.2 | 11 | MANE Select | |
| Ensembl | ENSP00000253108.3 | 11 | MANE Select | |
| Ensembl | ENSP00000468159.1 | 8 | Standard | |
| Ensembl | ENSP00000468313.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| eif3g | Danio rerio | Structure: pigment cell Quality: quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- RNA transport - Homo sapiens (human)
- Translation Factors
- Formation of the ternary complex, and subsequently, the 43S complex
- Translation initiation complex formation
- Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S
Biological Process
- formation of cytoplasmic translation initiation complex
- translational initiation
- viral translational termination-reinitiation
Molecular Function
- RNA binding
- translation initiation factor activity
- protein binding
Cellular Component
- nucleus
- cytoplasm
- cytosol
- eukaryotic translation initiation factor 3 complex
- eukaryotic 43S preinitiation complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000253108
- Coding exons
- 11
- Length
- 4904
- Individuals with no LoFs
- 117739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 117740
- p
- 0.00000425
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.17 | 126 | 216 | 0.584 | 0.0000146 | 2088 |
| Missense (PolyPhen) | 18 | 63.635 | 0.28286 | 633 | ||
| Synonymous | -1.00 | 101 | 89.0 | 1.14 | 0.00000650 | 606 |
| Loss of Function | 3.62 | 1 | 17.2 | 0.0580 | 7.28e-7 | 215 |
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) | 0.0000094 | 0.0000094 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre- initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF- 3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). This subunit can bind 18S rRNA. {ECO:0000255|HAMAP-Rule:MF_03006, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.164
- RVIS EVS
- -0.85
- RVIS percentile EVS
- 11.06
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.925
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |