EIF4EBP3
protein-codingeukaryotic translation initiation factor 4E binding protein 3
Gene summary
This gene encodes a member of the EIF4EBP family, which consists of proteins that bind to eukaryotic translation initiation factor 4E and regulate its assembly into EIF4F, the multi-subunit translation initiation factor that recognizes the mRNA cap structure. Read-through transcription from the neighboring upstream gene (MASK or ANKHD1) generates a transcript (MASK-BP3) that encodes a protein comprised of the MASK protein sequence for the majority of the protein and a different C-terminus due to an alternate reading frame for the EIF4EBP3 segments. [provided by RefSeq, Oct 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.9 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 EIF4EBP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003732.3. 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 | 4 | 4 | ||||
| missense | 13 | 2 | 15 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 19 | 2 | 0 | 21 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003723.1 | 3 | MANE Select | |
| Ensembl | ENSP00000308472.2 | 3 | MANE Select | |
| Ensembl | ENSP00000643865.1 | 3 | Standard | |
| Ensembl | ENSP00000805990.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- RNA transport - Homo sapiens (human)
- Translation Factors
Biological Process
- negative regulation of translational initiation
Molecular Function
- protein binding
- eukaryotic initiation factor 4E binding
- translation repressor activity
Cellular Component
- cytoplasm
- membrane
- eukaryotic translation initiation factor 4F complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000310331
- Coding exons
- 3
- Length
- 1913
- Individuals with no LoFs
- 124435
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 90
- Defined
- 124526
- p
- 0.000365
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0940 | 52 | 53.9 | 0.964 | 0.00000291 | 628 |
| Missense (PolyPhen) | 15 | 19.459 | 0.77087 | 239 | ||
| Synonymous | 0.394 | 19 | 21.3 | 0.892 | 0.00000104 | 209 |
| Loss of Function | -0.0857 | 5 | 4.80 | 1.04 | 2.89e-7 | 54 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00031 | rare |
| Latino/Admixed American | 0.000058 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.0012 | 0.00061 | notable |
| South Asian | 0.00049 | 0.00039 | rare |
| Other | 0.00033 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation. {ECO:0000250|UniProtKB:Q13541}.;
Recessive Scores
- pRec
- 0.112
Intolerance Scores
- RVIS EVS
- 0.01
- RVIS percentile EVS
- 54.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.557
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |