EIF4A3
eukaryotic translation initiation factor 4A3, the group of SSU processome|DEAD-box helicases|Spliceosomal Bact complex|Spliceosomal P complex|Exon junction complex
Basic information
Region (hg38): 17:80134369-80147151
Previous symbols: [ "DDX48" ]
Links
Phenotypes
GenCC
Source:
- Richieri Costa-Pereira syndrome (Definitive), mode of inheritance: AR
- Richieri Costa-Pereira syndrome (Moderate), mode of inheritance: AR
- Richieri Costa-Pereira syndrome (Supportive), mode of inheritance: AR
- Richieri Costa-Pereira syndrome (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Richieri-Costa-Pereira Syndrome | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Musculoskeletal | 24360810 |
| The genetic cause involves a noncoding expansion |
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn_genetic_diseases (20 variants)
- not_provided (14 variants)
- EIF4A3-related_disorder (4 variants)
- Richieri_Costa-Pereira_syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the EIF4A3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014740.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 12 | |||||
| missense | 22 | 23 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 0 | 22 | 8 | 4 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| EIF4A3 | protein_coding | protein_coding | ENST00000269349 | 12 | 11970 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000153 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.02 | 74 | 255 | 0.291 | 0.0000146 | 2698 |
| Missense in Polyphen | 20 | 113.12 | 0.17681 | 1178 | ||
| Synonymous | -0.814 | 106 | 95.9 | 1.11 | 0.00000578 | 782 |
| Loss of Function | 4.64 | 0 | 25.0 | 0.00 | 0.00000131 | 270 |
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) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: ATP-dependent RNA helicase (PubMed:16170325). Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:22961380, PubMed:28502770, PubMed:28076346). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Its RNA-dependent ATPase and RNA-helicase activities are induced by CASC3, but abolished in presence of the MAGOH-RBM8A heterodimer, thereby trapping the ATP- bound EJC core onto spliced mRNA in a stable conformation. The inhibition of ATPase activity by the MAGOH-RBM8A heterodimer increases the RNA-binding affinity of the EJC. Involved in translational enhancement of spliced mRNAs after formation of the 80S ribosome complex. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Shows higher affinity for single-stranded RNA in an ATP-bound core EJC complex than after the ATP is hydrolyzed. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the function is different from the established EJC assembly (PubMed:22203037). Involved in craniofacial development (PubMed:24360810). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:15034551, ECO:0000269|PubMed:16170325, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:17375189, ECO:0000269|PubMed:19409878, ECO:0000269|PubMed:22203037, ECO:0000269|PubMed:22961380, ECO:0000269|PubMed:24360810, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770}.;
- Pathway
- mRNA surveillance pathway - Homo sapiens (human);RNA transport - Homo sapiens (human);Spliceosome - Homo sapiens (human);Gene expression (Transcription);Cytokine Signaling in Immune system;RNA Polymerase II Transcription;Metabolism of RNA;Cleavage of Growing Transcript in the Termination Region ;RNA Polymerase II Transcription Termination;Immune System;mRNA Splicing - Major Pathway;Nonsense-Mediated Decay (NMD);Transport of Mature mRNA derived from an Intron-Containing Transcript;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Deadenylation of mRNA;Deadenylation-dependent mRNA decay;ISG15 antiviral mechanism;Antiviral mechanism by IFN-stimulated genes;Interferon Signaling;mRNA Splicing;mRNA 3,-end processing;Transport of Mature Transcript to Cytoplasm;Processing of Capped Intron-Containing Pre-mRNA
(Consensus)
Recessive Scores
- pRec
- 0.203
Intolerance Scores
- loftool
- rvis_EVS
- -0.63
- rvis_percentile_EVS
- 17.03
Haploinsufficiency Scores
- pHI
- 0.186
- hipred
- Y
- hipred_score
- 0.802
- ghis
- 0.614
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Eif4a3
- Phenotype
Gene ontology
- Biological process
- nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;mRNA splicing, via spliceosome;rRNA processing;RNA export from nucleus;mRNA export from nucleus;associative learning;response to organic cyclic compound;negative regulation of translation;mRNA 3'-end processing;exploration behavior;positive regulation of translation;embryonic cranial skeleton morphogenesis;cellular response to selenite ion;negative regulation of excitatory postsynaptic potential;regulation of translation at postsynapse, modulating synaptic transmission;negative regulation of selenocysteine incorporation;negative regulation of selenocysteine insertion sequence binding;cellular response to brain-derived neurotrophic factor stimulus
- Cellular component
- nucleoplasm;cytoplasm;cytosol;membrane;nuclear speck;dendrite;exon-exon junction complex;neuronal cell body;catalytic step 2 spliceosome;glutamatergic synapse;postsynaptic cytosol
- Molecular function
- RNA binding;mRNA binding;ATP-dependent RNA helicase activity;protein binding;ATP binding;poly(A) binding;selenocysteine insertion sequence binding;RNA stem-loop binding;ribonucleoprotein complex binding;translation regulator activity