EFL1
protein-codingelongation factor like GTPase 1, the group of Ribosomal biogenesis factors
Gene summary
Enables GTPase activity and ribosome binding activity. Involved in GTP metabolic process and cytosolic ribosome assembly. Predicted to be part of ribonucleoprotein complex. Predicted to be active in cytosol. Implicated in Shwachman-Diamond syndrome. [provided by Alliance of Genome Resources, Jul 2025]
- EFTUD1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~132.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0044205
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0044205
Submitter: ClinGen
EFL1 is located on chromosome 15 (15q25.2) and encodes the elongation factor like GTPase 1. This gene directly interacts with SBDS to release eukaryotic translation initiation factor 6 (eIF6) from the 60S ribosomal subunit for 80S ribosomal assembly (PMID: 341158470). EFL1 was first reported in relation to autosomal recessive (AR) EFL1-related Shwachman-Diamond syndrome in 2017 (Stepensky et al. 2017 PMID: 28331068). This syndrome is characterized by exocrine pancreatic dysfunction, hematopoietic abnormalities, short stature, and metaphyseal dysplasia. Eleven variants reported in 11 probands across 5 publications are included in this curation (PMIDs: 29970384; 34237744; 39379149; 28331068; 34115847). However, three of these probands are not scored either due to absence of sufficient clinical description or presence of de novo variant in commonly tested Shwachman-Diamond syndrome (SDS) genes (PMIDs: 34115847;34237744). The mechanism of disease is loss-of-function where pathogenic variants in the EFL1 gene result in failure of elf6 release from the 60S subunit, thereby impairing 80S ribosomal assembly and reducing protein synthesis. Of note, the c.3205A>G p.Thr1069Ala variant is speculated to result in somatic uniparental disomy in bone marrow conferring an acquired selective advantage in the context of inherited compound heterozygosity (PMID: 34115847). However, even this less deleterious EFL1 variant does not fully correct ribosome assembly and induces SDS features in cell line and animal models (PMID: 34115847). This gene-disease relationship is also supported by functional alteration in patient cells, non-human model organisms, biochemical evidence, and protein-protein interaction (PMIDs: 31151987; 34115847; 21536732; 24406167). Pathogenic EFL1 variants in patient cells are demonstrated to impede eIF6 release and attenuate translation (PMID: 31151987). The Efl1-K983R mouse line (Efl1K983R/K983R) exhibits impaired hematopoiesis, motor abnormalities, and cognitive deficits (PMID: 31151987). Furthermore, an orthologous model of compound heterozygosity recapitulates features of human disease with reduced hemoglobin, white blood cells, and platelets and impaired 80S ribosome assembly (PMID: 34115847). Zebrafish efl1 morphants model also recapitulates human SDS features, which are rescued by the human wild-type, but less by EFL1 p.Thr1069Ala mRNA (PMID: 34115847). SBDS and EFL1 are also shown to directly interact and catalyze the translational activation of ribosomes in eukaryotes (PMIDs: 24406167; 21536732). In summary, there is definitive evidence supporting the relationship between EFL1 and AR EFL1-related Shwachman-Diamond syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Childhood, Adolescent and Young Adult Cancer Predisposition GCEP on 02/10/2026 (SOP Version 12).
Inheritance Pattern: AR
Disease ID:MONDO:0009833
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0044205
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0044205
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Craniofacial; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic
Intervention: Allergy/Immunology/Infectious; Gastrointestinal; Hematologic
Rationale: Medical treatment (eg, pancreatic enzymes, fat-soluble vitamins) can be effective to treat pancreatic exocrine insufficiency; Blood/platelet transfusions may be necessary; Due to neutropenia and infectious risk, prophylactic measures (eg antibiotics), as well as early and aggressive treatment of infections, may be beneficial
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EFL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024580.6. 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 | 170 | 2 | 173 | ||
| missense | 1 | 6 | 268 | 16 | 1 | 292 |
| nonsense | 2 | 9 | 11 | |||
| start loss | 1 | 1 | ||||
| frameshift | 2 | 5 | 7 | |||
| splice donor/acceptor (+/-2bp) | 10 | 10 | ||||
| Total | 3 | 8 | 294 | 186 | 3 | 494 |
Highest pathogenic variant AF is 0.000024781797
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_078856.4 | 19 | MANE Select | |
| Ensembl | ENSP00000268206.7 | 19 | MANE Select | |
| RefSeq | NP_001035700.1 | 17 | Standard | |
| RefSeq | NP_001309773.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ribosome biogenesis in eukaryotes - Homo sapiens (human)
Biological Process
- translational elongation
- mature ribosome assembly
- GTP metabolic process
Molecular Function
- translation elongation factor activity
- GTPase activity
- GTP binding
- ribosome binding
Cellular Component
- cytosol
- ribonucleoprotein complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000268206
- Coding exons
- 19
- Length
- 132534
- Individuals with no LoFs
- 124719
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 77
- Defined
- 124796
- p
- 0.000309
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.25 | 507 | 593 | 0.855 | 0.0000296 | 7376 |
| Missense (PolyPhen) | 135 | 197.28 | 0.68431 | 2302 | ||
| Synonymous | 0.260 | 197 | 202 | 0.977 | 0.00000995 | 2114 |
| Loss of Function | 4.27 | 23 | 58.1 | 0.396 | 0.00000330 | 662 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00052 | 0.00045 | rare |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0.00070 | 0.00070 | rare |
| East Asian | 0.00017 | 0.00017 | rare |
| Finnish | 0.00037 | 0.00037 | rare |
| European (Non-Finnish) | 0.00035 | 0.00034 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the biogenesis of the 60S ribosomal subunit and translational activation of ribosomes. Together with SBDS, triggers the GTP-dependent release of EIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating EIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. Has low intrinsic GTPase activity. GTPase activity is increased by contact with 60S ribosome subunits. {ECO:0000269|PubMed:21536732}.;
Recessive Scores
- pRec
- 0.115
Intolerance Scores
- RVIS EVS
- 0.83
- RVIS percentile EVS
- 88.09
Essentials
- Essential (gene trap)
- N