EIF5A
protein-codingeukaryotic translation initiation factor 5A
Gene summary
Enables U6 snRNA binding activity. Involved in several processes, including cellular response to virus; positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator; and tumor necrosis factor-mediated signaling pathway. Located in annulate lamellae; cytosol; and nucleoplasm. Part of nuclear pore. Biomarker of colorectal cancer. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0859163
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0859163
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0859163
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0859163
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Craniofacial; Neurologic
Intervention: Cardiovascular
Rationale: Individuals may have congenital cardiovascular anomalies, and awareness may allow early identification and management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EIF5A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001970.5. 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 | 3 | 4 | 15 | 22 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | 1 | 5 | ||
| splice donor/acceptor (+/-2bp) | 2 | 5 | 7 | |||
| Total | 5 | 9 | 21 | 4 | 0 | 39 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001961.1 | 4 | MANE Select | |
| Ensembl | ENSP00000336776.8 | 4 | MANE Select | |
| RefSeq | NP_001137232.1 | 5 | Standard | |
| RefSeq | NP_001137233.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Translation Factors
- eIF5A regulation in response to inhibition of the nuclear export system
- Post-translational protein modification
- Metabolism of proteins
- Gamma carboxylation, hypusine formation and arylsulfatase activation
Biological Process
- mRNA export from nucleus
- translational frameshifting
- protein export from nucleus
- nucleocytoplasmic transport
- apoptotic process
Molecular Function
- RNA binding
- translation elongation factor activity
- protein binding
- U6 snRNA binding
- ribosome binding
Cellular Component
- nucleus
- annulate lamellae
- nuclear pore
- cytoplasm
- endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000336452
- Coding exons
- 5
- Length
- 5457
- Individuals with no LoFs
- 125746
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125748
- p
- 0.00000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.41 | 35 | 104 | 0.336 | 0.00000601 | 1199 |
| Missense (PolyPhen) | 0 | 20.38 | 0 | 266 | ||
| Synonymous | -1.83 | 56 | 41.1 | 1.36 | 0.00000276 | 353 |
| Loss of Function | 2.43 | 1 | 8.74 | 0.114 | 4.70e-7 | 112 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: mRNA-binding protein involved in translation elongation. Has an important function at the level of mRNA turnover, probably acting downstream of decapping. Involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity. With syntenin SDCBP, functions as a regulator of p53/TP53 and p53/TP53-dependent apoptosis. Regulates also TNF- alpha-mediated apoptosis. Mediates effects of polyamines on neuronal process extension and survival. May play an important role in brain development and function, and in skeletal muscle stem cell differentiation. Also described as a cellular cofactor of human T-cell leukemia virus type I (HTLV-1) Rex protein and of human immunodeficiency virus type 1 (HIV-1) Rev protein, essential for mRNA export of retroviral transcripts. {ECO:0000269|PubMed:15371445, ECO:0000269|PubMed:15452064, ECO:0000269|PubMed:16987817, ECO:0000269|PubMed:17187778, ECO:0000269|PubMed:17360499}.;
Recessive Scores
- pRec
- 0.298
Intolerance Scores
- LoFtool
- 0.286
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 49.39
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |