EIF6
eukaryotic translation initiation factor 6, the group of Ribosomal biogenesis factors
Basic information
Region (hg38): 20:35278907-35284985
Previous symbols: [ "EIF3A", "ITGB4BP" ]
Links
Phenotypes
GenCC
Source:
- Shwachman-Diamond syndrome (Limited), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the EIF6 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 14 | 14 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 14 | 1 | 0 |
Variants in EIF6
This is a list of pathogenic ClinVar variants found in the EIF6 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 20-35279591-T-C | not specified | Uncertain significance (Jan 24, 2024) | ||
| 20-35279702-C-A | not specified | Uncertain significance (Mar 23, 2022) | ||
| 20-35279702-C-G | not specified | Uncertain significance (May 24, 2024) | ||
| 20-35279726-T-C | not specified | Uncertain significance (Jun 23, 2023) | ||
| 20-35279747-C-T | not specified | Uncertain significance (Sep 05, 2024) | ||
| 20-35279997-T-C | not specified | Uncertain significance (Nov 03, 2023) | ||
| 20-35280021-T-C | Exstrophy-epispadias complex | Uncertain significance (-) | ||
| 20-35280058-C-T | not specified | Uncertain significance (Dec 07, 2021) | ||
| 20-35280117-T-A | not specified | Uncertain significance (Sep 22, 2023) | ||
| 20-35280684-G-A | Likely benign (Apr 01, 2024) | |||
| 20-35280724-C-T | not specified | Uncertain significance (Nov 09, 2024) | ||
| 20-35280752-T-C | not specified | Uncertain significance (Oct 05, 2023) | ||
| 20-35280769-C-T | not specified | Uncertain significance (Sep 21, 2021) | ||
| 20-35280791-C-T | not specified | Uncertain significance (Jun 23, 2023) | ||
| 20-35284207-G-A | not specified | Likely benign (Sep 11, 2024) | ||
| 20-35284212-T-C | not specified | Uncertain significance (Jul 21, 2024) | ||
| 20-35284245-G-A | not specified | Uncertain significance (Nov 14, 2024) | ||
| 20-35284388-A-G | not specified | Uncertain significance (Nov 25, 2024) | ||
| 20-35284435-T-C | not specified | Uncertain significance (Sep 14, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| EIF6 | protein_coding | protein_coding | ENST00000374450 | 6 | 6075 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.238 | 0.756 | 125742 | 0 | 6 | 125748 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.14 | 106 | 145 | 0.733 | 0.00000736 | 1594 |
| Missense in Polyphen | 16 | 38.353 | 0.41718 | 427 | ||
| Synonymous | 0.429 | 53 | 57.1 | 0.928 | 0.00000282 | 500 |
| Loss of Function | 2.35 | 3 | 11.7 | 0.257 | 5.87e-7 | 126 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000444 | 0.0000439 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. Behaves as a stimulatory translation initiation factor downstream insulin/growth factors. Is also involved in ribosome biogenesis. Associates with pre-60S subunits in the nucleus and is involved in its nuclear export. Cytoplasmic release of TIF6 from 60S subunits and nuclear relocalization is promoted by a RACK1 (RACK1)-dependent protein kinase C activity (PubMed:10085284, PubMed:14654845, PubMed:21536732). In tissues responsive to insulin, controls fatty acid synthesis and glycolysis by exerting translational control of adipogenic transcription factors such as CEBPB, CEBPD and ATF4 that have G/C rich or uORF in their 5'UTR. Required for ROS- dependent megakaryocyte maturation and platelets formation, controls the expression of mitochondrial respiratory chain genes involved in reactive oxygen species (ROS) synthesis (By similarity). Involved in miRNA-mediated gene silencing by the RNA- induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC (PubMed:17507929). Modulates cell cycle progression and global translation of pre-B cells, its activation seems to be rate-limiting in tumorigenesis and tumor growth (By similarity). {ECO:0000255|HAMAP-Rule:MF_03132, ECO:0000269|PubMed:10085284, ECO:0000269|PubMed:14654845, ECO:0000269|PubMed:17507929, ECO:0000269|PubMed:21536732}.;
- Pathway
- Ribosome biogenesis in eukaryotes - Homo sapiens (human);Translation Factors;Alpha6Beta4Integrin;eukaryotic protein translation
(Consensus)
Recessive Scores
- pRec
- 0.134
Intolerance Scores
- loftool
- 0.118
- rvis_EVS
- 0.04
- rvis_percentile_EVS
- 56.92
Haploinsufficiency Scores
- pHI
- 0.440
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.592
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.977
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Eif6
- Phenotype
- adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Gene ontology
- Biological process
- ribosomal subunit export from nucleus;regulation of glycolytic process;translational initiation;response to insulin;gene silencing by miRNA;miRNA mediated inhibition of translation;mature ribosome assembly;ribosomal large subunit biogenesis;regulation of fatty acid biosynthetic process;regulation of megakaryocyte differentiation;positive regulation of translation;assembly of large subunit precursor of preribosome;regulation of reactive oxygen species metabolic process
- Cellular component
- nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;preribosome, large subunit precursor;extracellular exosome
- Molecular function
- translation initiation factor activity;protein binding;ribosome binding;ribosomal large subunit binding