EIF3K
protein-codingeukaryotic translation initiation factor 3 subunit K, the group of Eukaryotic translation initiation factor 3
Gene summary
The 700-kD eukaryotic translation initiation factor-3 (eIF3) is the largest eIF and contains at least 12 subunits, including EIF2S12. eIF3 plays an essential role in translation by binding directly to the 40S ribosomal subunit and promoting formation of the 40S preinitiation complex (Mayeur et al., 2003 [PubMed 14519125]).[supplied by OMIM, Mar 2008]
- EIF3S12
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0100038
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EIF3K variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_013234.4. 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 | 1 | 1 | ||||
| missense | 38 | 38 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 42 | 0 | 0 | 42 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_037366.1 | 8 | MANE Select | |
| Ensembl | ENSP00000248342.3 | 8 | MANE Select | |
| RefSeq | NP_001287921.1 | 7 | Standard | |
| RefSeq | NP_001295322.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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
- Eukaryotic Translation Initiation
- Translation
Biological Process
- formation of cytoplasmic translation initiation complex
- translational initiation
- regulation of translational initiation
Molecular Function
- translation initiation factor activity
- protein binding
- ribosome binding
Cellular Component
- nucleus
- cytosol
- eukaryotic translation initiation factor 3 complex
- membrane
- eukaryotic 43S preinitiation complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000248342
- Coding exons
- 8
- Length
- 17861
- Individuals with no LoFs
- 125681
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 67
- Defined
- 125748
- p
- 0.000266
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.761 | 104 | 128 | 0.811 | 0.00000712 | 1452 |
| Missense (PolyPhen) | 21 | 26.182 | 0.80207 | 372 | ||
| Synonymous | -0.0963 | 54 | 53.1 | 1.02 | 0.00000330 | 391 |
| Loss of Function | 2.08 | 7 | 16.0 | 0.438 | 8.53e-7 | 163 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00065 | 0.00065 | rare |
| European (Non-Finnish) | 0.00018 | 0.00018 | rare |
| South Asian | 0.00062 | 0.00062 | rare |
| Other | 0.00016 | 0.00016 | rare |
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). {ECO:0000255|HAMAP-Rule:MF_03010, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.;
Recessive Scores
- pRec
- 0.203
Intolerance Scores
- LoFtool
- 0.448
- RVIS EVS
- 0.35
- RVIS percentile EVS
- 74.18
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.942
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |