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Showing EFTUD2 — SNU114 is a alias.

EFTUD2

116 kDa U5 small nuclear ribonucleoprotein component · UniProt Q15029

Length
972 aa
Mass
109.4 kDa
Annotated
2026-06-09
51 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EFTUD2 (Snu114/U5-116kD) is a highly conserved spliceosomal GTPase that acts as a central regulatory node in catalytic splicing and post-splicing-complex disassembly within the major spliceosome (PMID:22305528). It assembles into the U5 snRNP through its GTPase domain and direct interaction with Prp8, docking onto the 3' side of U5 snRNA internal loop 1 together with Brr2 (PMID:16540695, PMID:23857713). The crystal structure of the Snu114-Prp8 complex captures EFTUD2 in a GTP-bound conformation in which Prp8 binding abolishes its weak intrinsic GTPase activity, defining a Snu114-GTP-Prp8 module that serves as a relay station governing the same set of splicing events during spliceosome activation and disassembly (PMID:32196113); its C-terminus drives the conformational rearrangement with Prp8 that triggers U1 and U4 snRNP release to activate the spliceosome (PMID:15911574, PMID:16540695). Beyond catalytic core function, EFTUD2 directs alternative splicing of specific transcripts: it controls Mdm2 (exon 3) and pro-apoptotic Caspase3/Aifm1 isoforms, with loss causing intron retention and exon skipping transcriptome-wide (PMID:27899647, PMID:33601405, PMID:40448601). Haploinsufficiency depletes neural crest and neural progenitor pools through splicing errors that stabilize nuclear P53 and hyperactivate the p53 pathway, driving the craniofacial and neurodevelopmental defects of mandibulofacial dysostosis with microcephaly (PMID:22305528, PMID:27899647, PMID:33601405); P53-independent mis-splicing and lineage-specific outputs such as ferroptosis suppression in Purkinje cells also contribute to tissue phenotypes (PMID:36012294, PMID:39153477). EFTUD2 additionally tunes innate immunity by splicing-dependent regulation of RIG-I/MDA5, interferon-stimulated genes, and the TLR4-NF-κB cascade (PMID:25878102, PMID:31278373, PMID:37396299), and acts oncogenically in several cancers by regulating splicing of targets including Kif3a, MST1R/RON, and DDX41 and by stabilizing c-MYC against proteasomal degradation (PMID:38163859, PMID:40555777, PMID:40275081, PMID:40968608).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2005 High

    Established that the Snu114/EFTUD2 C-terminus and GTPase activity are functionally required for spliceosome activation rather than being passive structural features.

    Evidence Conditional lethal alleles, in vivo/in vitro splicing assays, and synthetic lethality with Brr2/Prp28 in yeast

    PMID:15911574

    Open questions at the time
    • Did not resolve the structural basis of the Prp8-Snu114 rearrangement
    • GTP hydrolysis cycle timing during catalysis not defined
  2. 2006 High

    Defined how EFTUD2 assembles into the U5 snRNP, showing the GTPase domain and Prp8 are both required for stable incorporation and that C-terminal function maps specifically to U4 release.

    Evidence Biochemical snRNP/spliceosome assembly in SNU114 mutant yeast extracts with Co-IP of Prp8 and U5 snRNA

    PMID:16540695

    Open questions at the time
    • Atomic-resolution view of the assembly interfaces lacking at this stage
    • Order of Prp8 vs U5 snRNA engagement not established
  3. 2008 High

    Placed Prp8/Snu114 centrally and Brr2 peripherally in the tri-snRNP, revealing structural dynamics consistent with conformational activation.

    Evidence Electron microscopy projection structure of genetically tagged S. cerevisiae tri-snRNP

    PMID:18953335

    Open questions at the time
    • Projection resolution insufficient for atomic contacts
    • Functional state of the captured conformers undefined
  4. 2012 High

    Linked EFTUD2 to human disease, establishing that haploinsufficiency of this spliceosomal GTPase causes mandibulofacial dysostosis with microcephaly.

    Evidence Whole-exome sequencing of 12 unrelated MFDM patients identifying null/frameshift alleles

    PMID:22305528

    Open questions at the time
    • Did not define which mis-splicing events drive the phenotype
    • Tissue-specific vulnerability of neural crest unexplained
  5. 2013 Medium

    Identified the U5 snRNA internal loop 1 3' side as the platform required for co-recruitment of Prp8, Snu114, and Brr2.

    Evidence Site-directed mutagenesis of U5 snRNA with Co-IP and synthetic lethal screening in yeast

    PMID:23857713

    Open questions at the time
    • Single-lab finding
    • Whether IL1 binding is direct or bridged by protein partners not resolved
  6. 2017 High

    Connected EFTUD2 loss to a transcriptome-wide splicing defect that activates the p53 pathway, providing the first mechanistic bridge between splicing failure and the developmental phenotype.

    Evidence Positional cloning, RNA-seq, and TUNEL in zebrafish eftud2 mutant

    PMID:27899647

    Open questions at the time
    • Specific causative mis-spliced transcripts not yet identified
    • Mechanism linking NMD failure to p53 activation undefined
  7. 2019 Medium

    Resolved the in vivo requirement for EFTUD2 in mammalian development, showing homozygous loss is pre-implantation lethal while heterozygotes model the dosage-sensitive disease.

    Evidence CRISPR/Cas9 exon 2 deletion mouse with Mendelian analysis and in situ hybridization

    PMID:31276534

    Open questions at the time
    • Molecular cause of pre-implantation lethality not dissected
    • Single-lab study
  8. 2019 High

    Demonstrated EFTUD2's role in innate immunity, showing it modulates the TLR4-NF-κB inflammatory response through alternative splicing of cascade components.

    Evidence Myeloid-specific conditional knockout mice with LPS challenge and splicing analysis

    PMID:31278373

    Open questions at the time
    • Exact NF-κB cascade transcripts mis-spliced not fully enumerated
    • Relationship to spliceosome core function unclear
  9. 2019 Medium

    Mapped a substrate-discriminating surface on Snu114 domain IVa where PP1 and Cwc21 bind competitively in a nucleotide-state-dependent manner, controlling splicing of a specific transcript subset.

    Evidence Yeast mutagenesis, nucleotide-state binding assays, and meiotic transcript splicing readout

    PMID:30672374

    Open questions at the time
    • Functional consequence of PP1 recruitment to the spliceosome not defined
    • Single-lab finding
  10. 2019 Medium

    Extended the p53-mediated mechanism to skeletal lineages, showing EFTUD2 deficiency impairs osteoblast/chondrocyte differentiation via TP53 activation.

    Evidence siRNA in human calvarial cells, zebrafish knockout, RNA-seq, and morpholino p53 rescue

    PMID:31806011

    Open questions at the time
    • Causative mis-spliced transcripts upstream of p53 not identified here
    • Single-lab study
  11. 2020 High

    Delivered the atomic basis of the relay-station model, showing Prp8 locks Snu114 in a GTP-bound state and that perturbing the shared GTP pocket alters a defined set of splicing events.

    Evidence Crystal structure of Snu114-Prp8, GTPase assays, and in vivo splicing with pocket mutants in yeast

    PMID:32196113

    Open questions at the time
    • Whether GTP exchange ever occurs during the cycle unresolved
    • Trigger for the conformational relay not defined
  12. 2020 High

    Pinpointed Mdm2 exon 3 skipping as a direct driver of P53 overactivation in neural crest, validated by Mdm2 and pifithrin-α rescue of craniofacial defects.

    Evidence Wnt1-Cre2 conditional knockout mice, RNA-seq, minigene assay, and dual rescue

    PMID:33601405

    Open questions at the time
    • Did not exclude additional contributing mis-splicing events
    • Extent of P53-independent contribution unaddressed
  13. 2020 Medium

    Resolved the molecular consequence of disease missense variants, partitioning them into protein-function-altering versus splicing-altering loss-of-function classes.

    Evidence Yeast Snu114 growth assays and minigene splicing assays for 19 MFDGA variants

    PMID:32333448

    Open questions at the time
    • Mechanism for variants without detectable defect unclear
    • Single-lab functional surrogate
  14. 2022 Medium

    Showed that p53 loss alone does not rescue craniofacial malformation, establishing that P53-independent mis-splicing also contributes to disease.

    Evidence Eftud2;Trp53 double conditional knockout with splicing analysis of P53-dependent and -independent transcripts

    PMID:36012294

    Open questions at the time
    • Functional impact of P53-independent targets (Synj2bp) not established
    • Single-lab study
  15. 2022 Medium

    Generalized neural crest progenitor depletion via apoptosis as the cellular basis of spliceosomopathy-associated MFD across multiple splicing factors.

    Evidence Morpholino knockdown of Eftud2/Snrpb/Txnl4a in Xenopus with neural crest marker and apoptosis assays

    PMID:35893124

    Open questions at the time
    • Did not identify EFTUD2-specific splicing targets in this system
    • Morpholino-based knockdown
  16. 2024 High

    Uncovered a p53-independent, lineage-specific role in which EFTUD2 suppresses ferroptosis to protect cerebellar Purkinje cells.

    Evidence Purkinje-cell-specific knockout mice, lipidomics, and pharmacological/genetic ferroptosis rescue with Atf4 pathway analysis

    PMID:39153477

    Open questions at the time
    • Whether Scd1/Gch1/Atf4 regulation is splicing-dependent not fully resolved
    • Generality beyond Purkinje cells unknown
  17. 2025 Medium

    Identified direct EFTUD2 binding to Caspase3 and Aifm1 transcripts to generate pro-apoptotic isoforms underlying cortical microcephaly.

    Evidence NSC-specific knockout mice, in utero electroporation, RNA co-IP, and full-length transcriptome sequencing

    PMID:40448601

    Open questions at the time
    • Direct vs spliceosome-mediated transcript binding not distinguished
    • Single-lab finding
  18. 2025 Medium

    Expanded the oncogenic splicing repertoire, linking EFTUD2 to Kif3a, MST1R/RON, and DDX41 isoform regulation across cancers.

    Evidence Conditional knockouts, siRNA/ASO knockdown, RNA-seq splicing analysis, and pathway reporter assays in medulloblastoma, ovarian, and other cancer models

    PMID:40275081 PMID:40555777 PMID:40968608

    Open questions at the time
    • Whether these reflect direct splicing regulation or core spliceosome function unclear
    • Each finding from a single lab
  19. 2024 Medium

    Revealed a non-splicing function in which EFTUD2 stabilizes c-MYC protein against ubiquitin-mediated degradation within a positive feedback loop driving chemoresistance.

    Evidence Reciprocal Co-IP, ubiquitination assay, ChIP, and luciferase reporter in colorectal cancer

    PMID:38163859

    Open questions at the time
    • Mechanism by which EFTUD2 blocks c-MYC ubiquitination not defined
    • Single-lab study
  20. 2023 Medium

    Extended splicing-dependent immune regulation to antiviral defense and microglial polarization, showing EFTUD2 controls ISG and inflammatory outputs independent of JAK-STAT.

    Evidence CRISPR knockout in hepatocytes, microglia-specific conditional knockout, and RIG-I-dependent ISG induction assays

    PMID:25878102 PMID:36204854 PMID:37396299

    Open questions at the time
    • Which ISG transcripts are direct splicing substrates not fully mapped
    • Mechanism of NF-κB cascade splicing regulation incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how EFTUD2 selects specific transcripts (Mdm2, Kif3a, Caspase3, ISGs) for regulated alternative splicing distinct from its constitutive core spliceosome role, and how its non-canonical c-MYC-stabilizing and ferroptosis-suppressing activities mechanistically arise.
  • No model distinguishing core spliceosome function from substrate-specific regulation
  • Structural basis of non-splicing protein-stabilization activity unknown
  • Human structural data for EFTUD2-containing tri-snRNP not in corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0003924 GTPase activity 3 GO:0140098 catalytic activity, acting on RNA 3 GO:0005198 structural molecule activity 2
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-5357801 Programmed Cell Death 3
Partners
BRR2CWC21DGUOK-AS1MYCPP1PRP8
Complex memberships
U5 snRNPspliceosomal tri-snRNP

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 EFTUD2 (U5-116kD) encodes a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly; haploinsufficiency causes mandibulofacial dysostosis with microcephaly (MFDM), establishing its essential role in the major spliceosome. Whole-exome sequencing identifying causative mutations (null alleles, frameshifts) in patients; consistent with haploinsufficiency across 12 unrelated individuals American journal of human genetics High 22305528
2005 The C-terminus of Snu114 (EFTUD2 ortholog) is required for spliceosome activation; C-terminal truncation allele snu114-60 was synthetically lethal with ATPases Brr2 and Prp28 required for U1 and U4 snRNP release, suggesting a rearrangement between Prp8 and the C-terminus of Snu114 leads to release of U1 and U4 snRNPs to activate the spliceosome. GTP binding/hydrolysis domain mutations blocked the first step of splicing in vivo and in vitro. Random mutagenesis to create conditional lethal alleles; in vivo and in vitro splicing assays; synthetic lethality analysis with PRP8, BRR2, PRP28, SAD1, BRR1 Genetics High 15911574
2006 Assembly of Snu114 (EFTUD2 ortholog) into the U5 snRNP requires both a functional GTPase domain and Prp8. GTPase domain mutations prevent Snu114 interaction with Prp8 and with U5 snRNA, blocking U5 snRNP assembly. The C-terminal truncation mutant assembles spliceosomes but blocks U4 snRNP release. Biochemical analysis of snRNP and spliceosome assembly in SNU114 mutant yeast extracts; co-immunoprecipitation of Snu114 with Prp8 and U5 snRNA RNA (New York, N.Y.) High 16540695
2008 In the yeast tri-snRNP EM structure, Prp8 and Snu114 (EFTUD2 ortholog) are located centrally, while Brr2 occupies a separate head domain; U4/U6 snRNP forms the arm domain. The head and arm domains adopt variable relative positions, suggesting structural dynamics during catalytic activation. Electron microscopy projection structure of S. cerevisiae tri-snRNP with genetically tagged proteins visualized by EM Nature structural & molecular biology High 18953335
2013 The U5 snRNA internal loop 1 (IL1), particularly its 3' side, is a platform required for Prp8, Snu114 (EFTUD2 ortholog), and Brr2 association with U5 snRNA during U5 snRNP assembly. Mutations in IL1 3' side caused the greatest reduction in association of all three proteins. Site-directed mutagenesis of U5 snRNA loop 1 and internal loop 1; in vivo functional assays; co-immunoprecipitation of Prp8, Snu114, Brr2 with U5 snRNA; synthetic lethal screening of brr2 and U5 snRNA mutants Journal of cellular biochemistry Medium 23857713
2017 Disruption of eftud2 in zebrafish leads to transcriptome-wide RNA splicing deficiency (intron retention and exon skipping), causing inadequate nonsense-mediated RNA decay and activation of the p53 pathway, resulting in increased apoptosis and mitosis of neural progenitors during brain development. Positional cloning of nonsense mutation; RNA-seq transcriptome analysis; functional analysis in zebrafish fn10a mutant; TUNEL apoptosis assay Nucleic acids research High 27899647
2015 EFTUD2 restricts HCV infection through an RIG-I/MDA5-dependent, JAK-STAT-independent pathway; EFTUD2 upregulates RIG-I and MDA5 expression by gene splicing, and its antiviral effect on interferon-stimulated gene induction was absent in RIG-I-knockdown or RIG-I-defective cells. siRNA knockdown; overexpression in Huh7 cells; RIG-I knockdown and RIG-I-defective cell lines as controls; measurement of ISG induction and HCV replication Journal of virology Medium 25878102
2019 Myeloid-specific knockout of Eftud2 suppresses NF-κB signaling activation in LPS-challenged macrophages; the mechanism involves EFTUD2-mediated alternative splicing of components of the TLR4–NF-κB cascade, thereby modulating innate immune inflammatory response. Myeloid-specific conditional knockout mouse model; LPS stimulation of macrophages; cytokine measurements; NF-κB pathway analysis; alternative splicing analysis of TLR4-NF-κB cascade components Mucosal immunology High 31278373
2019 Homozygous loss of Eftud2 causes pre-implantation lethality in mice; heterozygous mutants are viable with reduced EFTUD2 mRNA and protein levels. Eftud2 expression is enriched in the developing head and craniofacial regions. CRISPR/Cas9 deletion of exon 2; Mendelian frequency analysis at E3.5 and post-implantation; in situ hybridization for expression; ex vivo embryo culture PloS one Medium 31276534
2020 Only 4 of 19 MFDGA-associated EFTUD2 missense variants cause loss-of-function through altered protein function (assessed in yeast growth assays); 5 of the remaining 15 cause loss-of-function by altering EFTUD2 pre-mRNA splicing (predominantly exon skipping or cryptic splice site activation leading to a premature termination codon). Yeast functional growth assays modeling missense variants in S. cerevisiae Snu114; minigene splicing assay; bioinformatics prediction comparison Human mutation Medium 32333448
2021 Homozygous deletion of Eftud2 in neural crest cells causes craniofacial malformations via mis-splicing of Mdm2 (exon 3 skipping), leading to increased nuclear P53, upregulation of P53-target genes, and increased cell death. Overexpression of non-spliced Mdm2 attenuates P53 pathway overactivation in Eftud2 knockdown cells, and P53 inhibitor pifithrin-α improves craniofacial development in Eftud2-mutant embryos. Conditional Wnt1-Cre2 knockout mouse; RNAseq analysis; siRNA knockdown in O9-1 neural crest cells; minigene splicing assay; Mdm2 overexpression rescue; pifithrin-α treatment rescue Human molecular genetics High 33601405
2019 EFTUD2 deficiency inhibits proliferation, differentiation, and maturation of osteoblasts and chondrocytes via activation of the TP53 signaling pathway with increased phosphorylation of TP53 and upregulation of downstream targets (FAS, STEAP3, CASP3, P21, SESN1). P53 inhibition by morpholino reduced mortality in eftud2-null zebrafish. siRNA knockdown in human calvarial osteoblast and chondrocyte cells; zebrafish eftud2 knockout model; RNA-seq; western blot for phospho-TP53; morpholino p53 inhibition rescue Human genomics Medium 31806011
2020 Crystal structure of yeast Snu114 with the Snu114-binding region of Prp8 shows Snu114 in a GTP-bound conformation. The Prp8 Snu114-binding region abolishes Snu114's weak intrinsic GTPase activity. Exchange of GTP-contacting residues in Snu114 or Prp8 residues lining the Snu114 GTP-binding pocket leads to temperature-sensitive growth and affects the same set of splicing events in vivo, suggesting the Snu114-GTP-Prp8 module serves as a relay station during spliceosome activation and disassembly. Crystal structure determination of Snu114-Prp8 complex; GTPase activity assay; co-purification with endogenous GTP; yeast growth assays with GTP-contacting residue mutants; in vivo splicing analysis Nucleic acids research High 32196113
2019 Snu114 domain IVa directly interacts with protein phosphatase PP1 via a 'YGVQYK' binding motif; Cwc21 also binds this same motif in domain IVa, and these interactions are mutually exclusive. The affinity of Cwc21 and PP1 for Snu114 is influenced by the nucleotide-bound state of Snu114. A mutation in domain IVa causes a specific defect in splicing of meiotic gene transcripts (SPO22, AMA1, MER2) without affecting vegetative growth. Yeast mutagenesis; genetic and biochemical interaction assays; nucleotide-state dependent binding assays; in vivo splicing analysis of meiotic transcripts RNA biology Medium 30672374
2022 Craniofacial defects in Eftud2 neural-crest-specific homozygous mutant embryos are not rescued by simultaneous deletion of Trp53, despite reduced apoptosis. Both P53-regulated (Mdm2, Foxm1) and P53-independent (Synj2bp) transcripts show increased mis-splicing in double mutants, indicating that P53-independent splicing defects also contribute to craniofacial malformations. Double homozygous conditional knockout (Eftud2;Trp53) in neural crest cells; pifithrin-α treatment; SOX10 staining; analysis of Mdm2, Foxm1, Synj2bp, and Zmat3 splicing International journal of molecular sciences Medium 36012294
2022 Knockdown of Eftud2, Snrpb, or Txnl4a in Xenopus embryos causes defects in cranial neural crest cell formation, identifying neural crest progenitor depletion through apoptosis as the likely culprit for MFD associated with EFTUD2 haploinsufficiency. Morpholino knockdown in Xenopus; neural crest cell marker analysis; apoptosis assays at multiple developmental stages Journal of developmental biology Medium 35893124
2024 Purkinje-cell-specific ablation of Eftud2 causes ferroptosis and Purkinje cell degeneration; mechanistically, Eftud2 promotes Scd1 and Gch1 expression, upregulates monounsaturated fatty acid phospholipids, and enhances antioxidant activity to suppress ferroptosis. Transcription factor Atf4 is a downstream target mediating anti-ferroptosis effects in a p53-independent manner. Ferroptosis inhibition rescued cerebellar deficits. Conditional Purkinje-cell-specific Eftud2 knockout mice; ferroptosis assays; lipidomic analysis; pharmacological and genetic ferroptosis inhibition rescue; Atf4 pathway analysis Neuron High 39153477
2023 EFTUD2 mediates IFN anti-HBV effects through regulation of gene splicing for specific ISGs (Mx1, OAS1, PKR/EIF2AK2) without affecting Jak-STAT pathway gene expression or IFN receptors. EFTUD2 single allele knockout decreased ISG-encoded protein expression via impaired gene splicing; this was restored by EFTUD2 overexpression. CRISPR/Cas9 single allele knockout of EFTUD2 in HepG2.2.15 cells; mRNA sequencing; western blot for ISG proteins; EFTUD2 overexpression rescue experiment Mediators of inflammation Medium 37396299
2024 EFTUD2 physically interacts with and stabilizes c-MYC protein by preventing ubiquitin-mediated proteasomal degradation; c-MYC in turn directly binds the EFTUD2 promoter to activate its transcription, forming a positive feedback loop. EFTUD2-mediated 5-FU resistance in colorectal cancer is dependent on c-MYC stabilization. Co-immunoprecipitation; ubiquitination assay; chromatin immunoprecipitation (ChIP); dual luciferase reporter assay; molecular docking; rescue experiments with c-MYC Journal of experimental & clinical cancer research : CR Medium 38163859
2025 EFTUD2 directly interacts with Caspase3 and Aifm1 transcripts (shown by RNA co-immunoprecipitation) and regulates their alternative splicing to generate pro-apoptotic isoforms; NSC-specific Eftud2 knockout causes cortical disorganization and microcephaly through this apoptotic pathway. Conditional NSC-specific Eftud2 knockout mice; in utero electroporation of pathogenic EFTUD2 variants; RNA co-immunoprecipitation; full-length transcriptome sequencing; splicing assays; immunofluorescence Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 40448601
2025 EFTUD2 promotes efficient splicing of DDX41 mRNA and maintains oncogenic DDX41 protein expression; EFTUD2 knockdown induces DDX41 intron retention, reducing DDX41 protein and impairing malignant behavior of ovarian cancer cells. DDX41 knockdown partially phenocopied EFTUD2 knockdown. siRNA knockdown; in vitro and in vivo tumor assays; RNA-seq and alternative splicing event analysis; ASO-mediated EFTUD2 silencing British journal of cancer Medium 40555777
2025 Eftud2 promotes exon 10-11 skipping of Kif3a (a kinesin motor for primary cilia formation) in the cerebellum; this Kif3a isoform augments medulloblastoma cell proliferation by potentiating Gli2 transcriptional activity in the SHH signaling pathway. Multi-omics sequencing; conditional Eftud2 ablation in cerebellar granule precursor cells; functional assays in human medulloblastoma cells; SHH pathway and Gli2 reporter assays Cell death and differentiation Medium 40275081
2025 EFTUD2 interacts with the NDV V protein (mapped primarily to EFTUD2 residues 116-825); EFTUD2 overexpression enhances chicken MDA5 splicing efficiency and upregulates ISGs/IFN-β to suppress NDV replication. siRNA-mediated EFTUD2 knockdown promoted viral replication. Immunoprecipitation-mass spectrometry (IP-MS); co-immunoprecipitation; confocal microscopy; siRNA knockdown; overexpression assays; splicing efficiency measurement Poultry science Low 40580566
2020 EFTUD2 overexpression promotes HCC cell proliferation, migration, and EMT-like phenotype through enhanced STAT3 activation; stable knockdown of EFTUD2 via lentivirus was lethal for HCC cells, suggesting EFTUD2 is essential for HCC cell survival. STAT3 inhibitor partially blocked pro-malignant effects of EFTUD2 overexpression. siRNA and lentiviral knockdown; overexpression; in vitro proliferation/migration assays; xenograft mouse model; RNA sequencing with GSEA; STAT3 inhibitor (S3I-201) treatment Cell death & disease Medium 33024090
2025 lncRNA DGUOK-AS1 directly binds EFTUD2 and the deubiquitinating protein VCP-interacting protein 1, shielding EFTUD2 from ubiquitination and proteasomal degradation. EFTUD2, stabilized by this interaction, promotes exclusion of cassette exon 11 from MST1R (RON), producing the RON∆165 isoform that activates Akt/PKB signaling. RNA pull-down; RNA immunoprecipitation; co-immunoprecipitation; ubiquitination assay; western blot; RNA-seq for alternative splicing Cancer research and treatment Medium 40968608
2023 Eftud2 deficiency in microglia results in abnormal proliferation and promotes anti-inflammatory phenotype activation; Eftud2-mediated regulation of microglial pro-inflammatory/anti-inflammatory polarization in response to LPS is dependent on the NF-κB signaling pathway. Inducible microglia-specific conditional Eftud2 knockout (CX3CR1-CreER;Eftud2f/f); siRNA knockdown in BV2 microglia; immunofluorescence; western blot; NF-κB pathway analysis Neural regeneration research Medium 36204854

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Haploinsufficiency of a spliceosomal GTPase encoded by EFTUD2 causes mandibulofacial dysostosis with microcephaly. American journal of human genetics 173 22305528
2012 EFTUD2 haploinsufficiency leads to syndromic oesophageal atresia. Journal of medical genetics 88 23188108
2017 Spliceosomal protein eftud2 mutation leads to p53-dependent apoptosis in zebrafish neural progenitors. Nucleic acids research 68 27899647
2005 Genetic analysis reveals a role for the C terminus of the Saccharomyces cerevisiae GTPase Snu114 during spliceosome activation. Genetics 68 15911574
2012 "Mandibulofacial dysostosis with microcephaly" caused by EFTUD2 mutations: expanding the phenotype. American journal of medical genetics. Part A 62 23239648
2008 Localization of Prp8, Brr2, Snu114 and U4/U6 proteins in the yeast tri-snRNP by electron microscopy. Nature structural & molecular biology 60 18953335
2019 Spliceosome protein Eftud2 promotes colitis-associated tumorigenesis by modulating inflammatory response of macrophage. Mucosal immunology 48 31278373
2021 Mutation in Eftud2 causes craniofacial defects in mice via mis-splicing of Mdm2 and increased P53. Human molecular genetics 44 33601405
2013 Oto-facial syndrome and esophageal atresia, intellectual disability and zygomatic anomalies - expanding the phenotypes associated with EFTUD2 mutations. Orphanet journal of rare diseases 44 23879989
2015 EFTUD2 Is a Novel Innate Immune Regulator Restricting Hepatitis C Virus Infection through the RIG-I/MDA5 Pathway. Journal of virology 43 25878102
2006 Assembly of Snu114 into U5 snRNP requires Prp8 and a functional GTPase domain. RNA (New York, N.Y.) 36 16540695
2015 EFTUD2 deficiency in vertebrates: Identification of a novel human mutation and generation of a zebrafish model. Birth defects research. Part A, Clinical and molecular teratology 34 26118977
2020 EFTUD2 maintains the survival of tumor cells and promotes hepatocellular carcinoma progression via the activation of STAT3. Cell death & disease 26 33024090
2019 Loss of function mutation of Eftud2, the gene responsible for mandibulofacial dysostosis with microcephaly (MFDM), leads to pre-implantation arrest in mouse. PloS one 26 31276534
2018 Mandibulofacial dysostosis Guion-Almeida type caused by novel EFTUD2 splice site variants in two Asian children. Clinical dysmorphology 26 29381487
2020 EFTUD2 missense variants disrupt protein function and splicing in mandibulofacial dysostosis Guion-Almeida type. Human mutation 24 32333448
2019 EFTUD2 gene deficiency disrupts osteoblast maturation and inhibits chondrocyte differentiation via activation of the p53 signaling pathway. Human genomics 24 31806011
2022 The Core Splicing Factors EFTUD2, SNRPB and TXNL4A Are Essential for Neural Crest and Craniofacial Development. Journal of developmental biology 22 35893124
2014 Phenotype analysis of Polish patients with mandibulofacial dysostosis type Guion-Almeida associated with esophageal atresia and choanal atresia caused by EFTUD2 gene mutations. Journal of applied genetics 22 25387991
2013 Array-CGH is an effective first-tier diagnostic test for EFTUD2-associated congenital mandibulofacial dysostosis with microcephaly. Clinical genetics 18 24266672
2018 Novel De Novo EFTUD2 Mutations in 2 Cases With MFDM, Initially Suspected to Have Alternative Craniofacial Diagnoses. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 17 30343593
2017 Whole-exome sequencing identified a variant in EFTUD2 gene in establishing a genetic diagnosis. Orthodontics & craniofacial research 16 28643921
2014 Radioulnar Synostosis and Brain Abnormalities in a Patient With 17q21.31 Microdeletion Involving EFTUD2. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 15 24805776
2020 Novel Splice Site Pathogenic Variant of EFTUD2 Is Associated with Mandibulofacial Dysostosis with Microcephaly and Extracranial Symptoms in Korea. Diagnostics (Basel, Switzerland) 13 32408545
2020 A de novo synonymous variant in EFTUD2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case report. BMC medical genetics 12 32943010
2023 Spliceosomal GTPase Eftud2 regulates microglial activation and polarization. Neural regeneration research 11 36204854
2022 Craniofacial Defects in Embryos with Homozygous Deletion of Eftud2 in Their Neural Crest Cells Are Not Rescued by Trp53 Deletion. International journal of molecular sciences 11 36012294
2013 The U5 snRNA internal loop 1 is a platform for Brr2, Snu114 and Prp8 protein binding during U5 snRNP assembly. Journal of cellular biochemistry 11 23857713
2024 Spliceosomal GTPase Eftud2 deficiency-triggered ferroptosis leads to Purkinje cell degeneration. Neuron 10 39153477
2022 A novel de novo missense mutation in EFTUD2 identified by whole-exome sequencing in mandibulofacial dysostosis with microcephaly. Journal of clinical laboratory analysis 9 35435265
2024 The feedback loop of EFTUD2/c-MYC impedes chemotherapeutic efficacy by enhancing EFTUD2 transcription and stabilizing c-MYC protein in colorectal cancer. Journal of experimental & clinical cancer research : CR 8 38163859
2022 Clinical and molecular delineation of mandibulofacial dysostosis with microcephaly in six Korean patients: When to consider EFTUD2 analysis? European journal of medical genetics 6 35395430
2020 Spliceosome protein EFTUD2 is upregulated in the trophoblast of spontaneous miscarriage and hydatidiform mole. Journal of reproductive immunology 6 32447180
2024 Atypical mandibulofacial dysostosis with microcephaly diagnosed through the identification of a novel pathogenic mutation in EFTUD2. Molecular genetics & genomic medicine 5 38562046
2020 A Snu114-GTP-Prp8 module forms a relay station for efficient splicing in yeast. Nucleic acids research 5 32196113
2025 Interaction of Newcastle disease virus V protein with EFTUD2 modulates MDA5 pathway to suppress viral replication. Poultry science 4 40580566
2023 The Spliceosome Factor EFTUD2 Promotes IFN Anti-HBV Effect through mRNA Splicing. Mediators of inflammation 4 37396299
2022 A de novo start-loss in EFTUD2 associated with mandibulofacial dysostosis with microcephaly: case report. Cold Spring Harbor molecular case studies 4 35732499
2021 Association of Elongation Factor Tu GTP-binding Domain-containing 2 Gene (EFTUD2) Polymorphism with the Risk of Hepatitis B Virus Infection. Immunological investigations 4 34436958
2025 Spliceosome protein EFTUD2: A potential pathogenetic factor in tumorigenesis and some developmental defects (Review). Molecular medicine reports 3 40116087
2025 Alternative spliceosomal protein Eftud2 mediated Kif3a exon skipping promotes SHH-subgroup medulloblastoma progression. Cell death and differentiation 1 40275081
2025 EFTUD2 Regulates Cortical Morphogenesis via Modulation of Caspase-3 and Aifm1 Splicing Pathways. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 40448601
2025 Spliceosomal GTPase EFTUD2 mediates DDX41 intron retention to promote the malignant progression of ovarian cancer. British journal of cancer 1 40555777
2025 PROM1 and EFTUD2 Expression in High-Grade Clear Cell Renal Cell Carcinoma as a Molecular Marker for Survival Rate. International journal of molecular sciences 1 40650074
2026 [Genetic analysis of a de novo EFTUD2 variant causing Mandibulofacial dysostosis with microcephaly in a fetus]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 41918385
2026 Prenatal Ultrasound and Genetic Diagnosis of EFTUD2 Haploinsufficiency in Two Fetuses: A Case Series. The application of clinical genetics 0 41923825
2025 LncRNA CA13/EFTUD2/CA13 caused crossed beak by regulating the mandibular calcification in chicken. Poultry science 0 40480132
2025 A novel EFTUD2 splicing variant causing mandibulofacial dysostosis with microcephaly: a case report. Translational pediatrics 0 40688204
2025 LncRNA DGUOK-AS1 Promotes Bladder Cancer Progression by Enhancing EFTUD2 Stability. Cancer research and treatment 0 40968608
2025 Whole-Exome Sequencing Revealed a Novel De Novo Pathogenic EFTUD2 Variant in Mandibulofacial Dysostosis, Guion-Almeida Type: Reinforcing Links to Choanal and Oesophageal Atresia. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 0 41147426
2019 Mutagenesis of Snu114 domain IV identifies a developmental role in meiotic splicing. RNA biology 0 30672374

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