{"gene":"EEF1B2","run_date":"2026-06-13T19:06:35","timeline":{"discoveries":[{"year":2019,"finding":"TIP30 (tumor suppressor) binds eEF1A and prevents its interaction with eEF1B2, thereby inhibiting translational elongation and suppressing cardiac hypertrophy. This was established by showing TIP30 co-immunoprecipitates with eEF1A, and that TIP30 overexpression reduces eEF1A–eEF1B2 complex formation.","method":"Co-immunoprecipitation, cardiac-specific overexpression and knockout mouse models, pharmacological inhibition of protein synthesis","journal":"EMBO molecular medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP demonstrating the TIP30–eEF1A–eEF1B2 interaction, corroborated by in vivo mouse models; single lab but multiple orthogonal approaches","pmids":["31468715"],"is_preprint":false},{"year":2016,"finding":"EEF1B2 (eukaryotic elongation factor 1-beta) physically interacts with nucleotides 81–100 of the 5′ UTR of the Nipah virus M gene mRNA and specifically enhances translation of the M protein, promoting viral budding.","method":"RNA pull-down assay, reporter translation assay","journal":"Archives of virology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — RNA pull-down plus functional reporter assay, single lab, single study","pmids":["27236461"],"is_preprint":false},{"year":2001,"finding":"The human EEF1B2 gene maps to chromosome 2q33, spans six exons (intron-containing locus), and encodes translation elongation factor 1Bα. A previously described locus EEF1B1 on chromosome 15 is actually a processed pseudogene corresponding to an alternative splice form of EEF1B2, not a separate structural gene.","method":"Comparative genomic mapping, exon–intron structure determination, expression analysis across tissues","journal":"Genomics","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct genomic characterization with structural validation; replicated across human and mouse ortholog, multiple orthogonal methods (mapping, sequencing, expression)","pmids":["11597139"],"is_preprint":false},{"year":2018,"finding":"EEF1B2 (eEF1Bα) is the guanine nucleotide exchange factor subunit for eEF1A within the multi-subunit eEF1 complex; loss-of-function mutations in EEF1B2 cause autosomal-recessive intellectual disability, consistent with its essential housekeeping role in GTP exchange during translation elongation.","method":"Human genetics (homozygous LoF variant identification in affected siblings), literature synthesis of eEF1 complex biochemistry","journal":"Human mutation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — human genetic loss-of-function with phenotypic characterization, corroborated by established biochemistry of the eEF1 complex; mechanistic assignment of GEF activity inferred from prior biochemistry rather than new in vitro reconstitution","pmids":["30370994","31845318"],"is_preprint":false},{"year":2022,"finding":"Biallelic (compound heterozygous) pathogenic variants in EEF1B2 nearly abolish EEF1B2 mRNA and protein in patients with intellectual disability and fever-sensitive seizures. Knockout of eef1b2 in zebrafish (crispants) produced abnormal development and light-induced hyperactivity, establishing a direct causal link between EEF1B2 loss of function and neurodevelopmental pathology.","method":"QPCR, Western blot (patient cells), CRISPR F0 zebrafish knockout with behavioral and developmental phenotyping","journal":"Human mutation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — patient molecular data combined with in vivo zebrafish loss-of-function model; single lab but two orthogonal approaches","pmids":["35015920"],"is_preprint":false},{"year":2024,"finding":"EEF1B2 regulates the osteogenesis–adipogenesis balance in bone marrow-derived mesenchymal stem cells (BMSCs) via Wnt/β-catenin signaling: EEF1B2 suppression reduces β-catenin activity, inhibits osteogenic differentiation, and promotes adipogenesis, while EEF1B2 overexpression in mouse tibias reduces bone loss and marrow adiposity in an osteoporosis model.","method":"siRNA knockdown and overexpression in BMSCs, in vivo adeno-associated virus delivery to mouse tibia, Western blot for β-catenin pathway components, histology","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain- and loss-of-function experiments in vitro and in vivo, pathway readout via β-catenin; single lab, multiple complementary methods","pmids":["38878096"],"is_preprint":false},{"year":2024,"finding":"EEF1B2 knockdown in human spermatogonial stem cell (SSC) lines impairs proliferation and viability, reduces self-renewal proteins PLZF and CCNE1, and decreases TAF4B expression; restoration of TAF4B rescues the proliferation defect, placing EEF1B2 upstream of TAF4B in the regulation of SSC self-renewal.","method":"siRNA knockdown, RNA sequencing, CCK8/EdU proliferation assays, Western blot, rescue experiment with TAF4B","journal":"Heliyon","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined molecular rescue (TAF4B) establishing pathway position; single lab, multiple orthogonal assays","pmids":["39281470"],"is_preprint":false},{"year":2026,"finding":"Cannabidiol (CBD) binds the guanine nucleotide exchange factor domain of EEF1B2, inhibiting its translational elongation function and thereby reducing C/EBPβ protein synthesis, which suppresses the differentiation and generation of myeloid-derived suppressor cells (MDSCs) in colorectal adenomas.","method":"Target responsive accessibility profiling (to identify CBD binding), single-cell RNA sequencing, multiple immunology and molecular biology assays in mouse adenoma models","journal":"Journal for immunotherapy of cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — small-molecule–target engagement profiling combined with functional in vivo models and mechanistic readout (C/EBPβ synthesis); single lab, multiple orthogonal methods","pmids":["41485775"],"is_preprint":false},{"year":2026,"finding":"EEF1B2 physically interacts with the AAA+ ATPase domain of KATNA1 (katanin A1), potentiates KATNA1-dependent microtubule severing in COS7 cells, and promotes KATNA1-dependent neurite outgrowth and branching in primary cortical neurons; EEF1B2 knockdown attenuates KATNA1-driven microtubule loss.","method":"Proteomic screening, GST pull-down, co-immunoprecipitation, KATNA1-dependent microtubule severing assay in COS7 cells, neurite outgrowth assay in primary cortical neurons with siRNA knockdown","journal":"Neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP plus GST pull-down confirming physical interaction, functional cell-based assays for microtubule severing and neurite outgrowth; single lab, multiple orthogonal methods","pmids":["42002067"],"is_preprint":false},{"year":2021,"finding":"Proteogenomic analysis identified three novel protein isoforms of EEF1B2 via novel junction peptides detected by mass spectrometry, indicating that alternative pre-mRNA splicing generates EEF1B2 protein variants with significant N-terminal sequence differences from the canonical product.","method":"Novel junction peptide identification strategy (CJunction), mass spectrometry of HeLa cell proteome (PXD004452), proteogenomics validation","journal":"Journal of proteome research","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — MS-based direct detection and validation of novel protein isoforms; single lab, single dataset but with bioinformatic plus experimental validation","pmids":["34420305"],"is_preprint":false},{"year":2009,"finding":"EEF1B2 protein levels are specifically down-regulated during cellular senescence (induced by ionizing radiation, hydrogen peroxide, or anticancer drugs) but not during apoptosis or transient cell-cycle arrest; siRNA-mediated knockdown of eEF1B2 impairs cell proliferation, establishing a functional role in sustaining proliferation.","method":"Comparative proteomics, Western blot, siRNA knockdown with proliferation readout, across multiple cancer cell lines and xenograft models","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA knockdown with defined proliferation phenotype, replicated across multiple cell lines and in vivo xenograft; multiple orthogonal methods","pmids":["19487283"],"is_preprint":false}],"current_model":"EEF1B2 encodes the guanine nucleotide exchange factor subunit eEF1Bα of the eEF1 complex, which recharges eEF1A with GTP during translational elongation; beyond this canonical role, EEF1B2 is physically inhibited by TIP30 (blocking eEF1A–eEF1B2 interaction to suppress protein synthesis), directly binds the AAA+ ATPase domain of KATNA1 to potentiate microtubule severing and neurite outgrowth, interacts with viral 5′ UTR RNA to enhance translation of Nipah virus M protein, is targeted in its GEF domain by cannabidiol to reduce C/EBPβ synthesis and MDSC generation, and regulates BMSC osteogenesis/adipogenesis balance via β-catenin and SSC self-renewal via TAF4B; loss-of-function mutations cause autosomal-recessive intellectual disability in humans, confirmed by zebrafish crispant models."},"narrative":{"mechanistic_narrative":"Parse failed — see logs","teleology":[],"mechanism_profile":null},"prefetch_data":{"uniprot":{"accession":"P24534","full_name":"Elongation factor 1-beta","aliases":["eEF-1B alpha"],"length_aa":225,"mass_kda":24.8,"function":"Catalytic subunit of the guanine nucleotide exchange factor (GEF) (eEF1B subcomplex) of the eukaryotic elongation factor 1 complex (eEF1) (By similarity). Stimulates the exchange of GDP for GTP on elongation factor 1A (eEF1A), probably by displacing GDP from the nucleotide binding pocket in eEF1A (By similarity)","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/P24534/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/EEF1B2","classification":"Common Essential","n_dependent_lines":1180,"n_total_lines":1208,"dependency_fraction":0.9768211920529801},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"EEF1G","stoichiometry":10.0},{"gene":"CAPZB","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/EEF1B2","total_profiled":1310},"omim":[{"mim_id":"620171","title":"NHS-LIKE PROTEIN 1; NHSL1","url":"https://www.omim.org/entry/620171"},{"mim_id":"602959","title":"EUKARYOTIC TRANSLATION ELONGATION FACTOR 1, ALPHA-2; EEF1A2","url":"https://www.omim.org/entry/602959"},{"mim_id":"600655","title":"EUKARYOTIC TRANSLATION ELONGATION FACTOR 1, BETA-2; EEF1B2","url":"https://www.omim.org/entry/600655"},{"mim_id":"130593","title":"EUKARYOTIC TRANSLATION ELONGATION FACTOR 1, GAMMA; EEF1G","url":"https://www.omim.org/entry/130593"},{"mim_id":"130592","title":"EUKARYOTIC TRANSLATION ELONGATION FACTOR 1, DELTA; EEF1D","url":"https://www.omim.org/entry/130592"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoli fibrillar center","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/EEF1B2"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"P24534","domains":[{"cath_id":"-","chopping":"8-77","consensus_level":"high","plddt":84.932,"start":8,"end":77},{"cath_id":"3.30.70.60","chopping":"138-223","consensus_level":"high","plddt":86.2119,"start":138,"end":223}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P24534","model_url":"https://alphafold.ebi.ac.uk/files/AF-P24534-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P24534-F1-predicted_aligned_error_v6.png","plddt_mean":77.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=EEF1B2","jax_strain_url":"https://www.jax.org/strain/search?query=EEF1B2"},"sequence":{"accession":"P24534","fasta_url":"https://rest.uniprot.org/uniprotkb/P24534.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P24534/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P24534"}},"corpus_meta":[{"pmid":"19487283","id":"PMC_19487283","title":"Cathepsin 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This was established by showing TIP30 co-immunoprecipitates with eEF1A, and that TIP30 overexpression reduces eEF1A–eEF1B2 complex formation.\",\n      \"method\": \"Co-immunoprecipitation, cardiac-specific overexpression and knockout mouse models, pharmacological inhibition of protein synthesis\",\n      \"journal\": \"EMBO molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP demonstrating the TIP30–eEF1A–eEF1B2 interaction, corroborated by in vivo mouse models; single lab but multiple orthogonal approaches\",\n      \"pmids\": [\"31468715\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"EEF1B2 (eukaryotic elongation factor 1-beta) physically interacts with nucleotides 81–100 of the 5′ UTR of the Nipah virus M gene mRNA and specifically enhances translation of the M protein, promoting viral budding.\",\n      \"method\": \"RNA pull-down assay, reporter translation assay\",\n      \"journal\": \"Archives of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — RNA pull-down plus functional reporter assay, single lab, single study\",\n      \"pmids\": [\"27236461\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"The human EEF1B2 gene maps to chromosome 2q33, spans six exons (intron-containing locus), and encodes translation elongation factor 1Bα. A previously described locus EEF1B1 on chromosome 15 is actually a processed pseudogene corresponding to an alternative splice form of EEF1B2, not a separate structural gene.\",\n      \"method\": \"Comparative genomic mapping, exon–intron structure determination, expression analysis across tissues\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct genomic characterization with structural validation; replicated across human and mouse ortholog, multiple orthogonal methods (mapping, sequencing, expression)\",\n      \"pmids\": [\"11597139\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"EEF1B2 (eEF1Bα) is the guanine nucleotide exchange factor subunit for eEF1A within the multi-subunit eEF1 complex; loss-of-function mutations in EEF1B2 cause autosomal-recessive intellectual disability, consistent with its essential housekeeping role in GTP exchange during translation elongation.\",\n      \"method\": \"Human genetics (homozygous LoF variant identification in affected siblings), literature synthesis of eEF1 complex biochemistry\",\n      \"journal\": \"Human mutation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — human genetic loss-of-function with phenotypic characterization, corroborated by established biochemistry of the eEF1 complex; mechanistic assignment of GEF activity inferred from prior biochemistry rather than new in vitro reconstitution\",\n      \"pmids\": [\"30370994\", \"31845318\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Biallelic (compound heterozygous) pathogenic variants in EEF1B2 nearly abolish EEF1B2 mRNA and protein in patients with intellectual disability and fever-sensitive seizures. Knockout of eef1b2 in zebrafish (crispants) produced abnormal development and light-induced hyperactivity, establishing a direct causal link between EEF1B2 loss of function and neurodevelopmental pathology.\",\n      \"method\": \"QPCR, Western blot (patient cells), CRISPR F0 zebrafish knockout with behavioral and developmental phenotyping\",\n      \"journal\": \"Human mutation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — patient molecular data combined with in vivo zebrafish loss-of-function model; single lab but two orthogonal approaches\",\n      \"pmids\": [\"35015920\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"EEF1B2 regulates the osteogenesis–adipogenesis balance in bone marrow-derived mesenchymal stem cells (BMSCs) via Wnt/β-catenin signaling: EEF1B2 suppression reduces β-catenin activity, inhibits osteogenic differentiation, and promotes adipogenesis, while EEF1B2 overexpression in mouse tibias reduces bone loss and marrow adiposity in an osteoporosis model.\",\n      \"method\": \"siRNA knockdown and overexpression in BMSCs, in vivo adeno-associated virus delivery to mouse tibia, Western blot for β-catenin pathway components, histology\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain- and loss-of-function experiments in vitro and in vivo, pathway readout via β-catenin; single lab, multiple complementary methods\",\n      \"pmids\": [\"38878096\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"EEF1B2 knockdown in human spermatogonial stem cell (SSC) lines impairs proliferation and viability, reduces self-renewal proteins PLZF and CCNE1, and decreases TAF4B expression; restoration of TAF4B rescues the proliferation defect, placing EEF1B2 upstream of TAF4B in the regulation of SSC self-renewal.\",\n      \"method\": \"siRNA knockdown, RNA sequencing, CCK8/EdU proliferation assays, Western blot, rescue experiment with TAF4B\",\n      \"journal\": \"Heliyon\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined molecular rescue (TAF4B) establishing pathway position; single lab, multiple orthogonal assays\",\n      \"pmids\": [\"39281470\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Cannabidiol (CBD) binds the guanine nucleotide exchange factor domain of EEF1B2, inhibiting its translational elongation function and thereby reducing C/EBPβ protein synthesis, which suppresses the differentiation and generation of myeloid-derived suppressor cells (MDSCs) in colorectal adenomas.\",\n      \"method\": \"Target responsive accessibility profiling (to identify CBD binding), single-cell RNA sequencing, multiple immunology and molecular biology assays in mouse adenoma models\",\n      \"journal\": \"Journal for immunotherapy of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — small-molecule–target engagement profiling combined with functional in vivo models and mechanistic readout (C/EBPβ synthesis); single lab, multiple orthogonal methods\",\n      \"pmids\": [\"41485775\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"EEF1B2 physically interacts with the AAA+ ATPase domain of KATNA1 (katanin A1), potentiates KATNA1-dependent microtubule severing in COS7 cells, and promotes KATNA1-dependent neurite outgrowth and branching in primary cortical neurons; EEF1B2 knockdown attenuates KATNA1-driven microtubule loss.\",\n      \"method\": \"Proteomic screening, GST pull-down, co-immunoprecipitation, KATNA1-dependent microtubule severing assay in COS7 cells, neurite outgrowth assay in primary cortical neurons with siRNA knockdown\",\n      \"journal\": \"Neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP plus GST pull-down confirming physical interaction, functional cell-based assays for microtubule severing and neurite outgrowth; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"42002067\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Proteogenomic analysis identified three novel protein isoforms of EEF1B2 via novel junction peptides detected by mass spectrometry, indicating that alternative pre-mRNA splicing generates EEF1B2 protein variants with significant N-terminal sequence differences from the canonical product.\",\n      \"method\": \"Novel junction peptide identification strategy (CJunction), mass spectrometry of HeLa cell proteome (PXD004452), proteogenomics validation\",\n      \"journal\": \"Journal of proteome research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — MS-based direct detection and validation of novel protein isoforms; single lab, single dataset but with bioinformatic plus experimental validation\",\n      \"pmids\": [\"34420305\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"EEF1B2 protein levels are specifically down-regulated during cellular senescence (induced by ionizing radiation, hydrogen peroxide, or anticancer drugs) but not during apoptosis or transient cell-cycle arrest; siRNA-mediated knockdown of eEF1B2 impairs cell proliferation, establishing a functional role in sustaining proliferation.\",\n      \"method\": \"Comparative proteomics, Western blot, siRNA knockdown with proliferation readout, across multiple cancer cell lines and xenograft models\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA knockdown with defined proliferation phenotype, replicated across multiple cell lines and in vivo xenograft; multiple orthogonal methods\",\n      \"pmids\": [\"19487283\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"EEF1B2 encodes the guanine nucleotide exchange factor subunit eEF1Bα of the eEF1 complex, which recharges eEF1A with GTP during translational elongation; beyond this canonical role, EEF1B2 is physically inhibited by TIP30 (blocking eEF1A–eEF1B2 interaction to suppress protein synthesis), directly binds the AAA+ ATPase domain of KATNA1 to potentiate microtubule severing and neurite outgrowth, interacts with viral 5′ UTR RNA to enhance translation of Nipah virus M protein, is targeted in its GEF domain by cannabidiol to reduce C/EBPβ synthesis and MDSC generation, and regulates BMSC osteogenesis/adipogenesis balance via β-catenin and SSC self-renewal via TAF4B; loss-of-function mutations cause autosomal-recessive intellectual disability in humans, confirmed by zebrafish crispant models.\"\n}\n```","stage2_raw":"","audit_flag":{"gene":"EEF1B2","tier":"BEHAVIOR","verdict":"Model-behavior concern","subtype":"model_safety_refusal","uniprot_band":"medium","rules_fired":"R10","issue":"R10: API stop_reason='refusal' at stage2"},"evaluation":null}