EIF3E
protein-codingeukaryotic translation initiation factor 3 subunit E, the group of Eukaryotic translation initiation factor 3
Gene summary
Enables RNA binding activity and cadherin binding activity. Contributes to translation initiation factor activity. Involved in nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; positive regulation of translation; and translational initiation. Located in PML body and cytosol. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Jul 2025]
- INT6
- EIF3S6
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~280.7 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 EIF3E variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001568.3. 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 | 15 | 15 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 3 | 3 | ||||
| splice donor/acceptor (+/-2bp) | 10 | 10 | ||||
| Total | 0 | 0 | 30 | 0 | 0 | 30 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001559.1 | 13 | MANE Select | |
| Ensembl | ENSP00000220849.5 | 13 | MANE Select | |
| Ensembl | ENSP00000429327.1 | 2 | Standard | |
| Ensembl | ENSP00000430678.2 | 12 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| eif3ea | Danio rerio | Structure: melanocyte Quality: decreased pigmentation abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- RNA transport - Homo sapiens (human)
- Hepatitis C - Homo sapiens (human)
- Translation Factors
- Formation of the ternary complex, and subsequently, the 43S complex
- Translation initiation complex formation
Biological Process
- nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
- formation of cytoplasmic translation initiation complex
- translational initiation
- regulation of translational initiation
- positive regulation of translation
Molecular Function
- RNA binding
- translation initiation factor activity
- protein binding
- cadherin binding
- protein N-terminus binding
Cellular Component
- chromatin
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000220849
- Coding exons
- 13
- Length
- 234118
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125746
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.13 | 97 | 231 | 0.421 | 0.0000110 | 2961 |
| Missense (PolyPhen) | 29 | 84.411 | 0.34356 | 1074 | ||
| Synonymous | -0.744 | 83 | 74.8 | 1.11 | 0.00000351 | 762 |
| Loss of Function | 3.29 | 7 | 24.7 | 0.284 | 0.00000110 | 326 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00023 | 0.00022 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000082 | 0.000079 | rare |
| South Asian | 0.000038 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: 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). Required for nonsense-mediated mRNA decay (NMD); may act in conjunction with UPF2 to divert mRNAs from translation to the NMD pathway (PubMed:17468741). May interact with MCM7 and EPAS1 and regulate the proteasome-mediated degradation of these proteins (PubMed:17310990, PubMed:17324924). {ECO:0000255|HAMAP-Rule:MF_03004, ECO:0000269|PubMed:17310990, ECO:0000269|PubMed:17324924, ECO:0000269|PubMed:17468741, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.;
Recessive Scores
- pRec
- 0.156
Intolerance Scores
- LoFtool
- 0.513
- RVIS EVS
- -0.27
- RVIS percentile EVS
- 33.97
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.781
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |