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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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EFL1
elongation factor like GTPase 1
Chromosome 15 Β· 15q25.2
NCBI Gene: 79631Ensembl: ENSG00000140598.17HGNC: HGNC:25789UniProt: Q7Z2Z2
45PubMed Papers
21Diseases
0Drugs
6Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
GTPase activityprotein bindingribosome bindingcytosolic ribosome assemblyShwachman-Diamond syndrome 2Shwachman-Diamond syndromegenetic disordersevere congenital neutropenia
✦AI Summary

EFL1 encodes a GTPase that plays a critical role in ribosome biogenesis and maturation 1. EFL1 functions in concert with the Shwachman-Bodian-Diamond syndrome (SBDS) protein to catalyze the release of eukaryotic initiation factor 6 (eIF6) from 60S ribosomal subunits, which is the final step required for ribosome maturation and translation competence 12. The protein exhibits GTPase activity that is stimulated by SBDS through direct interaction mediated by EFL1's intrinsically disordered insertion domain and SBDS domains II-III 1. EFL1 is evolutionarily related to elongation factors EF-2 and EF-G, having originated through gene duplication from EF-2 proteins and subsequently specialized in ribosome maturation 3. Functionally, EFL1 shows species-specificity and possible co-evolution with SBDS and the 60S ribosomal subunit 3. Disease-associated mutations in EFL1 cause Shwachman-Diamond syndrome type 2, a ribosomopathy characterized by neutropenia, pancreatic insufficiency, and increased leukemia risk 45. These mutations impair mature ribosome formation and compromise protein synthesis 5. In SDS patients, chromosome 15 aberrations that increase EFL1 gene dosage can provide somatic genetic rescue 6.

Sources cited
1
EFL1 is a GTPase that directly interacts with SBDS to release eIF6 from 60S ribosomal subunits through its intrinsically disordered insertion domain
PMID: 24406167
2
EFL1 and SBDS work together to mediate the final maturation step of 60S ribosomal subunit for translation competence
PMID: 36009035
3
EFL1 proteins evolved from EF-2 through gene duplication and show species-specificity with functional co-evolution
PMID: 34453201
4
EFL1 mutations are associated with Shwachman-Diamond syndrome, a ribosomopathy affecting multiple organs
PMID: 30413969
5
Biallelic EFL1 variants impair mature ribosome formation and protein synthesis, causing severe SDS
PMID: 39379149
6
Chromosome 15 aberrations increasing EFL1 gene dosage can provide somatic genetic rescue in SDS patients
PMID: 37608017
Disease Associationsβ“˜21
Shwachman-Diamond syndrome 2Open Targets
0.69Moderate
Shwachman-Diamond syndromeOpen Targets
0.57Moderate
genetic disorderOpen Targets
0.41Moderate
severe congenital neutropeniaOpen Targets
0.37Weak
intelligenceOpen Targets
0.33Weak
substance-related disorderOpen Targets
0.25Weak
autism spectrum disorderOpen Targets
0.25Weak
attention deficit hyperactivity disorderOpen Targets
0.24Weak
diabetes mellitusOpen Targets
0.16Weak
type 2 diabetes mellitusOpen Targets
0.16Weak
Alzheimer diseaseOpen Targets
0.16Weak
ImmunodeficiencyOpen Targets
0.12Weak
Benign familial choreaOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.07Suggestive
Ataxia - oculomotor apraxia type 1Open Targets
0.05Suggestive
gliomaOpen Targets
0.05Suggestive
early-onset generalized limb-onset dystoniaOpen Targets
0.05Suggestive
spastic paraplegia 72b, autosomal recessiveOpen Targets
0.05Suggestive
Abnormality of the skeletal systemOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.04Suggestive
Shwachman-Diamond syndrome 2UniProt
Pathogenic Variants6
NM_024580.6(EFL1):c.1612-2A>GLikely pathogenic
Shwachman-Diamond syndrome 2
β˜…β˜†β˜†β˜†2025
NM_024580.6(EFL1):c.2260C>T (p.Arg754Ter)Likely pathogenic
Shwachman-Diamond syndrome 2|Shwachman syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 754
NM_024580.6(EFL1):c.1514T>C (p.Phe505Ser)Likely pathogenic
Shwachman-Diamond syndrome 2|Shwachman syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 505
NM_024580.6(EFL1):c.89A>G (p.His30Arg)Likely pathogenic
Shwachman-Diamond syndrome 2|Shwachman syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 30
NM_024580.6(EFL1):c.2647T>G (p.Cys883Gly)Pathogenic
Shwachman-Diamond syndrome 2
β˜†β˜†β˜†β˜†2022β†’ Residue 883
NM_024580.6(EFL1):c.2478dup (p.Gly827fs)Pathogenic
Shwachman-Diamond syndrome 2
β˜†β˜†β˜†β˜†2022β†’ Residue 827
View on ClinVar β†—
Related Genes
MRPS6Protein interaction100%MRPS9Protein interaction100%MRPL36Protein interaction100%MRPS16Protein interaction100%MRPS12Protein interaction100%MRPL19Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Heart
94%
Lung
69%
Bone Marrow
64%
Liver
52%
Ovary
43%
Gene Interaction Network
Click a node to explore
EFL1MRPS6MRPS9MRPL36MRPS16MRPS12MRPL19
PROTEIN STRUCTURE
Preparing viewer…
PDB5ANB Β· 4.10 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.72LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.59 [0.48–0.72]
RankingsWhere EFL1 stands among ~20K protein-coding genes
  • #9,440of 20,598
    Most Researched45
  • #3,405of 5,498
    Most Pathogenic Variants6
  • #5,526of 17,882
    Most Constrained (LOEUF)0.72
Genes detectedEFL1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Convergent somatic evolution commences in utero in a germline ribosomopathy.
PMID: 37608017
Nat Commun Β· 2023
1.00
2
Evolutionary and functional relationships in the ribosome biogenesis SBDS and EFL1 protein families.
PMID: 34453201
Mol Genet Genomics Β· 2021
0.90
3
The metabolic basis of inherited neutropenias.
PMID: 38049194
Br J Haematol Β· 2024
0.80
4
Shwachman-Diamond Syndrome: Molecular Mechanisms and Current Perspectives.
PMID: 30413969
Mol Diagn Ther Β· 2019
0.70
5
Reduced EIF6 dosage attenuates TP53 activation in models of Shwachman-Diamond syndrome.
PMID: 39964763
J Clin Invest Β· 2025
0.60