EIF4A2
protein-codingeukaryotic translation initiation factor 4A2, the group of DEAD-box helicases|MicroRNA protein coding host genes|Small nucleolar RNA protein coding host genes
Gene summary
Enables ATP hydrolysis activity. Involved in negative regulation of RNA-dependent RNA polymerase activity. Located in perinuclear region of cytoplasm. Implicated in neurodevelopmental disorder with hypotonia and speech delay. [provided by Alliance of Genome Resources, Jul 2025]
- EIF4F
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0957541
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0957541
Submitter: Ambry Genetics
Inheritance Pattern: SD
Disease ID:MONDO:0957541
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0957541
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0957541
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Neurologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EIF4A2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001967.4. 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 | 4 | 7 | 1 | 12 | ||
| missense | 3 | 10 | 51 | 64 | ||
| nonsense | 3 | 3 | ||||
| start loss | 3 | 3 | ||||
| frameshift | 1 | 2 | 19 | 22 | ||
| splice donor/acceptor (+/-2bp) | 1 | 10 | 11 | |||
| Total | 4 | 13 | 90 | 7 | 1 | 115 |
Highest pathogenic variant AF is 0.0000037174307
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001958.2 | 11 | MANE Select | |
| Ensembl | ENSP00000326381.5 | 11 | MANE Select | |
| Ensembl | ENSP00000413529.1 | 11 | Standard | |
| Ensembl | ENSP00000392686.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- RNA transport - Homo sapiens (human)
- Translation Factors
- Translation initiation complex formation
- Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S
- Cytokine Signaling in Immune system
Biological Process
- translational initiation
- regulation of translational initiation
- viral process
- negative regulation of RNA-directed 5'-3' RNA polymerase activity
- cellular response to leukemia inhibitory factor
Molecular Function
- RNA binding
- translation initiation factor activity
- ATP-dependent RNA helicase activity
- helicase activity
- protein binding
Cellular Component
- cytosol
- eukaryotic translation initiation factor 4F complex
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000323963
- Coding exons
- 11
- Length
- 6696
- Individuals with no LoFs
- 125743
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125748
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.90 | 60 | 224 | 0.268 | 0.0000113 | 2704 |
| Missense (PolyPhen) | 6 | 73.67 | 0.081444 | 967 | ||
| Synonymous | -2.41 | 100 | 73.7 | 1.36 | 0.00000358 | 755 |
| Loss of Function | 4.26 | 1 | 23.1 | 0.0433 | 0.00000116 | 271 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon.;
Recessive Scores
- pRec
- 0.142
Intolerance Scores
- LoFtool
- 0.183
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 38.28
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |