Affinage

NOVA2

RNA-binding protein Nova-2 · UniProt Q9UNW9

Length
492 aa
Mass
49.0 kDa
Annotated
2026-06-10
80 papers in source corpus 24 papers cited in narrative 24 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

NOVA2 is a KH-domain RNA-binding protein that binds YCAY-containing pre-mRNAs to control alternative splicing programs in both neurons and vascular endothelium (PMID:9789075, PMID:27223325). It was first defined as a neuron-enriched POMA autoantigen with sequence-specific RNA binding distinct from its paralog NOVA1 (PMID:9789075), and its KH3 domain adopts an open-faced beta-sheet sandwich that contacts target RNA through an invariant Gly-X-X-Gly loop (PMID:10368286). In the developing brain NOVA2 directs neuronal migration by toggling a Dab1 RNA switch in reelin signaling (PMID:20620871) and drives a cell-type-specific axon-guidance splicing program required for corpus callosum formation and motoneuron outgrowth, phenotypes absent in Nova1-null mice (PMID:27223325, PMID:30638744); this splicing regulation is coupled to intron retention that can sequester the splicing factor PTBP2 (PMID:30638744), and NOVA2 additionally promotes circRNA biogenesis by binding YCAY clusters in flanking introns to enhance backsplicing (PMID:34157123). Beyond the nervous system, NOVA2 is expressed in endothelial cells where it controls vascular lumen formation via Par-complex splicing (PMID:26446569), constrains Erk/Mapk signaling to time lymphatic specification through Prox1 (PMID:31014480), and generates pro-angiogenic soluble L1CAM (L1-ΔTM) by skipping the L1CAM transmembrane exon, acting through FGFR1 signaling (PMID:30829570). NOVA2 expression is itself regulated transcriptionally by STAT3/p300-driven H3K27 acetylation and post-transcriptionally by m6A-dependent mRNA decay (PMID:37534933, PMID:41922577). De novo frameshift variants that replace the C-terminal KH domain reduce RNA binding and splicing activity and fail to rescue neurite and axon-pathfinding defects, causing a neurodevelopmental disorder (PMID:32197073, PMID:35607920).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 High

    Established NOVA2 as a sequence-specific RNA-binding protein, distinct from NOVA1, defining the molecular activity from which all downstream functions follow.

    Evidence RNA selection and filter-binding assays on a POMA-autoantigen cDNA, with in situ expression mapping

    PMID:10735272 PMID:9789075

    Open questions at the time
    • RNA consensus motif not yet defined at this stage
    • no functional splicing target identified
  2. 1999 High

    Provided the atomic basis for KH-domain RNA recognition, showing how the conserved Gly-X-X-Gly loop and KH fold engage target RNA.

    Evidence X-ray crystallography of NOVA2 and NOVA1 KH3 domains

    PMID:10368286

    Open questions at the time
    • no RNA-bound co-crystal in this study
    • biological relevance of crystallographic KH3 tetramers untested
  3. 2007 Medium

    Demonstrated that NOVA2 regulates a defined neuronal splicing event in a genotype-dependent manner, linking it to ion-channel transcript processing.

    Evidence Minigene splicing assays plus human neocortex RT-PCR for SCN1A

    PMID:17436242

    Open questions at the time
    • direct binding to SCN1A pre-mRNA not shown
    • physiological consequence of altered SCN1A isoform untested
  4. 2010 High

    Defined the first in vivo developmental function, showing NOVA2 controls neuronal migration through a Dab1 RNA switch in reelin signaling.

    Evidence HITS-CLIP, exon-junction arrays, in utero electroporation and rescue epistasis in Nova2-null mice

    PMID:20620871

    Open questions at the time
    • mechanism linking Dab1.7bc isoform to migration machinery not fully resolved
  5. 2016 High

    Separated NOVA2 from NOVA1 functionally, establishing a paralog-specific axon-guidance splicing program with distinct neuroanatomical phenotypes.

    Evidence Isoform-specific HITS-CLIP and RNA-seq with parallel Nova1-/- and Nova2-/- mouse comparison

    PMID:27223325

    Open questions at the time
    • basis for paralog target selectivity not defined
    • individual guidance-transcript contributions not dissected
  6. 2019 High

    Revealed cell-type resolution of NOVA2 splicing and a second regulatory layer, coupling alternative splicing to intron retention and PTBP2 sequestration.

    Evidence cTag-CLIP and conditional knockout mice with behavioral and histological analysis

    PMID:30638744

    Open questions at the time
    • functional impact of PTBP2 sequestration not quantified per target
    • synapse-formation mechanism incompletely mapped
  7. 2019 High

    Extended NOVA2 beyond neurons, establishing endothelial roles in lumen formation, lymphatic timing, and pro-angiogenic L1CAM isoform generation.

    Evidence Zebrafish/mouse vascular loss-of-function, endothelial siRNA, direct L1CAM pre-mRNA binding, FGFR1 inhibition, phosphoproteomics

    PMID:26446569 PMID:30829570 PMID:31014480

    Open questions at the time
    • how a neuronal splicing factor is deployed in endothelium not explained
    • full endothelial target catalog not defined
  8. 2021 High

    Identified a function beyond linear splicing, showing NOVA2 promotes circRNA biogenesis via intronic YCAY clusters.

    Evidence Nova2 vs Nova1 knockout circRNA profiling, CLIP, and YCAY-mutant backsplicing reporter

    PMID:34157123

    Open questions at the time
    • functional roles of the affected circRNAs untested
    • generality of YCAY-driven backsplicing across loci not exhaustively mapped
  9. 2020 High

    Connected NOVA2 to human disease, showing C-terminal frameshift variants act as partial loss-of-function alleles causing a neurodevelopmental disorder.

    Evidence Patient exomes, RNA-binding and splicing assays, neurite outgrowth, and zebrafish axon-pathfinding rescue

    PMID:32197073 PMID:35607920

    Open questions at the time
    • genotype-phenotype spectrum not fully resolved
    • which mis-splicing events drive pathology not pinpointed
  10. 2023 Medium

    Defined how NOVA2 levels are set, establishing m6A-dependent decay and STAT3/p300-driven transcription as opposing regulatory inputs.

    Evidence MeRIP-seq with METTL14/YTHDF2 manipulation in hepatic stellate cells; ChIP for STAT3/H3K27ac at the NOVA2 promoter

    PMID:37534933 PMID:41922577

    Open questions at the time
    • m6A readers/writers differ across studies (YTHDF2 vs YTHDF1)
    • regulatory crosstalk between transcriptional and decay control untested
  11. 2026 High

    Implicated NOVA2 splicing in cancer progression, including SMAD4 exon skipping that sustains TGF-β signaling and RapGEF6 splicing linked to tumor angiogenesis.

    Evidence RNA-seq splicing, ubiquitination and Co-IP assays, in vivo metastasis (lung adenocarcinoma); endothelial RNA-seq plus IHC (gastric cancer)

    PMID:37175811 PMID:39279925 PMID:41922577

    Open questions at the time
    • direct NOVA2 binding to each cancer target not always shown
    • Wnt-activation mechanism in HCC unresolved
  12. 2025 Medium

    Linked NOVA2 to repeat-expansion neurodegeneration, showing pathogenic AUUUC/UUUCA RNAs sequester NOVA2 into nuclear foci and disrupt its splicing program.

    Evidence Patient iPSC-neurons and zebrafish models, colocalization, NOVA2 knockdown/overexpression rescue (some preprints)

    PMID:41850906 PMID:bio_10.1101_2025.08.26.672304 PMID:bio_10.1101_2025.09.03.673996

    Open questions at the time
    • direct affinity of NOVA2 for repeat RNA not quantified
    • two findings remain preprints
    • extent of splicing-program loss in patient neurons not fully mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NOVA2 target selectivity is partitioned between neuronal and endothelial contexts, and how condensate composition with partners like CELF2/SFPQ shapes splicing outcomes, remains unresolved.
  • NOVA2-specific contribution to CELF2/SFPQ condensate splicing not directly tested
  • no unified model linking cell-type expression to distinct target repertoires

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0140098 catalytic activity, acting on RNA 4
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-162582 Signal Transduction 3
Partners
CELF2PTBP2SFPQ

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 NOVA2 was identified as a neuron-specific KH-type RNA-binding protein autoantigen in POMA patients. RNA selection and nitrocellulose filter-binding assays demonstrated that NOVA2 binds RNA with high affinity and with sequence specificity distinct from NOVA1. NOVA2 is expressed at high levels in neurons during development and in adulthood, with a largely reciprocal expression pattern to NOVA1 (high in neocortex and hippocampus). RNA selection assay, nitrocellulose filter-binding assay, cDNA cloning with POMA antisera, in situ hybridization Proceedings of the National Academy of Sciences of the United States of America High 9789075
1997 NOVA2 (originally named ANOVA) maps to chromosome 19q13.3 and encodes a brain-expressed RNA-binding protein with three KH domains closely homologous to NOVA1. Northern blots showed expression restricted to brain (2.5 kb mRNA), with no tumor-specific alterations detected in gliomas by Southern blotting or SSCP. Exon amplification, cDNA library screening, Northern blot, in situ hybridization, Southern blotting, SSCP Neurogenetics Medium 10735272
1999 X-ray crystal structures of the KH3 domains of NOVA2 (at 2.0 Å) and NOVA1 (at 2.6 Å) were determined. The KH3 domain forms a compact protease-resistant open-faced sandwich of three-stranded antiparallel beta sheet topped by three alpha helices. In both Nova crystals, the lattice is composed of symmetric tetramers of KH3 domains created by two dimer interfaces, providing insights into how multiple KH domains may interact. The invariant Gly-X-X-Gly segment implicated in RNA-binding and the variable region loop conformations are visible. X-ray crystallography (multiple isomorphous replacement and molecular replacement) Structure High 10368286
2001 pasilla, the Drosophila homologue of human NOVA1 and NOVA2, is a nuclear RNA-binding protein that regulates splicing (localized to nuclear puncta) and is required for normal apical secretion in salivary glands. Loss of pasilla causes morphological defects and apical secretion failure without disrupting epithelial polarity or internalization. Genetic screen, immunofluorescence localization, loss-of-function mutant phenotypic analysis Developmental biology Medium 11784037
2007 NOVA2 regulates the alternative splicing of SCN1A in a cis-acting polymorphism-dependent manner. In human temporal neocortex and in a cellular minigene system, higher NOVA2 expression increased the proportion of the neonatal SCN1A splice form; the effect was larger in the AA genotype at IVS5N+5. No effect of NOVA2 was observed on alternative splicing of 17 other neuronal genes tested. Quantitative RT-PCR in human brain tissue, minigene expression system in cells, correlation of NOVA2 expression with splice variant proportions American journal of human genetics Medium 17436242
2010 NOVA2 regulates neuronal migration of late-generated cortical and Purkinje neurons by controlling an RNA switch in disabled-1 (Dab1) signaling. HITS-CLIP and exon junction array identified an alternatively spliced Dab1 isoform (Dab1.7bc) as the key Nova2-dependent reelin-pathway target. In utero electroporation showed Dab1.7bc was sufficient to induce neuronal migration defects in wild-type mice and to exacerbate defects when Dab1 levels were reduced; Dab1 overexpression mitigated defects in Nova2 null mice. HITS-CLIP, exon junction array, in utero electroporation, Nova2 knockout mice, epistasis rescue experiments Neuron High 20620871
2014 Molecular dynamics simulations reveal that the KH3 domain of NOVA2 likely recognizes its target RNA (human glycine receptor α2 RNA) through a conformational selection mechanism (with induced fit not fully excluded). The invariant Gly-Lys-Gly-Gly loop moves toward the RNA upon binding while the C-terminal domain moves away. Hydrophobic and hydrogen bonding interactions, rather than dominant electrostatic interactions, drive specific recognition. Molecular dynamics simulation in explicit solvent, Kolmogorov-Smirnov P-test, principal component analysis The journal of physical chemistry. B Low 25300025
2015 NOVA2 (previously considered neural cell-specific) is expressed in endothelial cells during angiogenesis. Nova2 depletion in vivo disrupts vascular lumen formation. In cultured endothelial cells, Nova2 depletion impairs apical distribution and downstream signaling of the Par polarity complex, resulting in altered endothelial cell polarity required for lumen formation. These defects are linked to alternative splicing changes in Nova2 target exons affecting the Par complex and its regulators. In vivo zebrafish/mouse vascular studies, siRNA knockdown in cultured endothelial cells, immunofluorescence, splicing analysis Nature communications High 26446569
2016 NOVA2 uniquely (distinct from NOVA1) regulates alternative splicing of a coordinate set of axon guidance-related transcripts during cortical development. NOVA2-specific HITS-CLIP and RNA-seq from Nova2-/- but not Nova1-/- mouse cortex revealed NOVA2-specific splicing targets. Nova2-/- mice have agenesis of the corpus callosum and axonal outgrowth defects specific to ventral motoneurons and efferent innervation of the cochlea; Nova1-/- mice lack these phenotypes. NOVA1- and NOVA2-specific HITS-CLIP, RNA-seq, Nova1-/- and Nova2-/- knockout mice, neuroanatomical analysis eLife High 27223325
2019 NOVA2, expressed in endothelial cells, binds directly to L1CAM pre-mRNA and is necessary and sufficient for skipping of the L1CAM transmembrane domain exon, generating a soluble L1CAM isoform (L1-ΔTM). L1-ΔTM exerts angiogenic function via autocrine and paracrine activities requiring fibroblast growth factor receptor-1 (FGFR1) signaling. NOVA2 and L1-ΔTM are overexpressed in ovarian cancer vasculature. RNA binding assay (direct NOVA2–L1CAM pre-mRNA interaction), splicing minigene/overexpression assays, endothelial cell functional assays (tube formation, migration), FGFR1 inhibitor experiments eLife High 30829570
2019 NOVA2 constrains Erk/Mapk signaling in vascular endothelial cells by selectively regulating pre-mRNA splicing of signaling pathway components and phosphoproteins, thereby limiting lymphatic progenitor specification. Nova2-deficient zebrafish endothelial cells display increased Mapk/Erk signaling, and Prox1 expression (a lymphatic fate specifier) is dynamically controlled by Erk signaling. Loss of Nova2 results in premature, expanded, and prolonged lymphatic specification. Zebrafish forward genetic screen, Nova2 knockout, phosphoproteomics/splicing analysis in human endothelial cells, Erk signaling assays, Prox1 expression analysis Developmental cell High 31014480
2019 NOVA2-mediated differential alternative splicing in excitatory versus inhibitory cortical neurons regulates: (1) cortical laminar development, (2) cerebellar motor coordination, and (3) synapse formation. cTag-CLIP from Nova2 conditional knockout mice revealed cell-type-specific NOVA2 regulatory actions on the same transcripts expressed in different neurons. NOVA2-regulated alternative splicing is coupled to regulation of intron retention in hundreds of transcripts, which can sequester the trans-acting splicing factor PTBP2. NOVA2 cTag-CLIP (cell-type-specific CLIP), Nova2 conditional knockout mice, RNA-seq, behavioral and histological analysis Neuron High 30638744
2020 De novo frameshift variants in NOVA2 that add a proline-rich C-terminal extension replacing the last KH RNA binding domain cause a neurodevelopmental disorder. The variant protein shows decreased ability to bind target RNA sequences and to regulate target alternative splicing events. It fails to complement NOVA2 loss-of-function effects on neurite outgrowth in vitro and fails to rescue retinotectal axonal pathfinding defects in Nova2 ortholog-deficient zebrafish. Patient exome sequencing, NOVA2 downregulation in human neural cells with RNA-seq (41 differentially spliced genes identified), neurite outgrowth assay in vitro, zebrafish axonal pathfinding rescue experiment, RNA binding assays American journal of human genetics High 32197073
2021 NOVA2 globally promotes circular RNA (circRNA) biogenesis in the developing mouse brain; global circRNA levels are reduced in embryonic cortex of Nova2 but not Nova1 knockout mice. In isolated inhibitory and excitatory cortical neurons, NOVA2 loss causes even more dramatic circRNA reduction. NOVA2 promotes backsplicing of circEfnb2 via YCAY cluster binding sites in both flanking introns, as demonstrated by CLIP and mutagenesis of a backsplicing reporter. Nova2 and Nova1 knockout mice, circRNA profiling from RNA-seq, backsplicing reporter with YCAY cluster mutagenesis, CLIP (cross-linking and immunoprecipitation) Nucleic acids research High 34157123
2022 Truncating NOVA2 variants (including those at KH1 and KH3 domains) negatively affect alternative splicing regulation, as shown in HeLa cells transfected with wildtype vs. mutant NOVA2 cDNA. A distal variant causing partial removal of KH3 had a milder functional effect. These findings support pathogenic role of splicing disruption in NOVA2-related neurodevelopmental disorder. Exome sequencing, transfection of wildtype and mutant NOVA2 cDNA in HeLa cells, splicing assays Human mutation Medium 35607920
2022 NOVA2 regulates blood-brain barrier permeability in endothelial cells. NOVA2 overexpression reduces the half-life of the lncRNA PART1, thereby stabilizing PPP2R3A mRNA. PART1 destabilizes PPP2R3A mRNA by interacting with STAU1. Reduced PPP2R3A leads to increased p-NFκB-p65, which decreases tight junction protein expression and increases barrier permeability. siRNA knockdown and overexpression in endothelial cells, PART1 half-life measurement, barrier permeability assay, tight junction protein expression (Western blot), co-IP/interaction assays Gene Medium 34990795
2023 METTL14-induced m6A methylation of NOVA2 mRNA promotes its degradation through YTHDF2-mediated mRNA decay. Depletion of METTL14 in hepatic stellate cells (HSCs) decreases m6A deposition on NOVA2 mRNA, reducing YTHDF2-dependent degradation and increasing NOVA2 levels, thereby exacerbating liver fibrosis. NOVA2 overexpression prevents HSC activation and liver fibrosis progression. MeRIP-seq combined with RNA-seq, METTL14 knockdown/overexpression in HSC lines, AAV-mediated in vivo knockdown, CCK8/EDU proliferation assays, Transwell migration assay Hepatology communications Medium 37534933
2023 NOVA2 upregulation in endothelial cells generates novel alternative splicing transcripts including altered splicing of RapGEF6 (Rap Guanine Nucleotide Exchange Factor 6). NOVA2 is upregulated in endothelial cells of gastric cancer and this AS of RapGEF6 is associated with NOVA2 expression, tumor angiogenesis, and poor patient outcome. RNA-seq after NOVA2 upregulation in endothelial cells, RT-PCR splicing analysis, immunohistochemistry in gastric cancer patient samples International journal of molecular sciences Medium 37175811
2024 NOVA2 promotes liver cancer stem cell (CSC) self-renewal and carcinogenesis via the Wnt pathway. METTL3/YTHDF1-dependent m6A methylation upregulates NOVA2 expression in hepatocellular carcinoma. Suppression of the Wnt pathway desensitizes NOVA2-overexpressing HCC cells to lenvatinib-induced apoptosis. Real-time PCR, in vitro CSC self-renewal and carcinogenesis assays, Wnt pathway inhibitor experiments, m6A methylation analysis Journal of gastrointestinal oncology Low 39279925
2025 In a zebrafish SCA37 model, NOVA2 overexpression rescues embryonic motor neuron axonal outgrowth defects caused by AUUUC repeat RNA, indicating that NOVA2 functional disruption by AUUUC RNA aggregates underlies axonal defects. NOVA2 colocalization with AUUUC repeat RNA foci was established, and NOVA2 knockdown promoted foci formation, while NOVA2 overexpression rescued axonal pathfinding. Zebrafish embryo model (transient ATTTC repeat RNA expression), NOVA2 overexpression rescue, immunofluorescence colocalization, NOVA2 knockdown bioRxivpreprint Medium bio_10.1101_2025.08.26.672304
2025 AUUUC repeat RNA (from ATTTC repeat expansion in SCA37) sequesters NOVA2 in aberrant nuclear aggregates in human neural stem cells and iPSC-neurons. NOVA2 was identified as a key RNA-binding protein interacting with AUUUC repeat RNA. NOVA2 knockdown promoted formation of AUUUC repeat RNA foci, and significant colocalization of iron and NOVA2 was observed at AUUUC repeat foci, a pattern absent in control cells. Human neural stem cell overexpression of ATTTC repeat, immunofluorescence colocalization, NOVA2 knockdown, RNA-binding protein identification, synchrotron X-ray fluorescence for iron detection bioRxivpreprint Medium bio_10.1101_2025.09.03.673996
2026 STAT3 promotes NOVA2 transcription by facilitating histone acetyltransferase p300-mediated H3K27 acetylation at the NOVA2 promoter, enabling STAT3 binding. NOVA2 in turn induces exon 6-7 skipping in SMAD4, generating a truncated isoform (Δ-SMAD4) that evades β-TrCP-mediated ubiquitination while retaining ability to complex with SMAD3 and sustain TGF-β/SMAD signaling, thereby promoting EMT and lung adenocarcinoma metastasis. Bioinformatic analysis of clinical data, NOVA2 depletion in vitro (EMT, migration, invasion assays) and in vivo (metastasis), ChIP for H3K27ac and STAT3 at NOVA2 promoter, RNA-seq for SMAD4 splicing, ubiquitination assay, Co-IP for SMAD3-Δ-SMAD4 complex Oncogene High 41922577
2026 NOVA2 interacts with (UUUCA) repeat RNA in FCMTE. The (UUUCA)exp RNA disrupts the normal nuclear distribution pattern of NOVA2. Knockdown of NOVA2 promotes formation of (UUUCA)exp RNA foci. Shared synaptic-related alternative splicing pathway changes are observed in both FCMTE1-iPSC-neurons and known NOVA target genes, suggesting sequestration of NOVA2 by repeat RNA contributes to pathology. iPSC-neurons from FCMTE1 patients, RNA foci detection, NOVA2 immunofluorescence/distribution, NOVA2 knockdown, alternative splicing analysis Movement disorders Medium 41850906
2024 CELF2 co-condensates with NOVA2 and SFPQ to coordinate regulation of Tau exon 10 alternative splicing. TurboID proximity labeling identified NOVA2 as an interactor of CELF2 through its intrinsically disordered region (IDR). The composition of splicing factor condensates, including NOVA2, determines alternative splicing outcomes. TurboID proximity labeling, co-condensation assays, alternative splicing assays in mouse brain bioRxivpreprint Low bio_10.1101_2024.11.02.621395

Source papers

Stage 0 corpus · 80 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 ANOVA-like differential expression (ALDEx) analysis for mixed population RNA-Seq. PloS one 607 23843979
1998 The neuronal RNA-binding protein Nova-2 is implicated as the autoantigen targeted in POMA patients with dementia. Proceedings of the National Academy of Sciences of the United States of America 191 9789075
2010 Nova2 regulates neuronal migration through an RNA switch in disabled-1 signaling. Neuron 148 20620871
2019 MiR-7-5p suppresses tumor metastasis of non-small cell lung cancer by targeting NOVA2. Cellular & molecular biology letters 126 31832068
2016 NOVA2-mediated RNA regulation is required for axonal pathfinding during development. eLife 110 27223325
2014 Identification of bacteriophage virion proteins by the ANOVA feature selection and analysis. Molecular bioSystems 106 24931825
2004 Using ANOVA to analyze microarray data. BioTechniques 106 15335204
1999 Crystal structures of Nova-1 and Nova-2 K-homology RNA-binding domains. Structure (London, England : 1993) 104 10368286
2007 Nova2 interacts with a cis-acting polymorphism to influence the proportions of drug-responsive splice variants of SCN1A. American journal of human genetics 87 17436242
2003 Using ANOVA for gene selection from microarray studies of the nervous system. Methods (San Diego, Calif.) 86 14597312
2012 Inferring gene regulatory networks by ANOVA. Bioinformatics (Oxford, England) 74 22467911
2021 NOVA2 regulates neural circRNA biogenesis. Nucleic acids research 69 34157123
2015 Phylogenetic ANOVA: The Expression Variance and Evolution Model for Quantitative Trait Evolution. Systematic biology 68 26169525
2019 Differential NOVA2-Mediated Splicing in Excitatory and Inhibitory Neurons Regulates Cortical Development and Cerebellar Function. Neuron 63 30638744
2018 Human biomarker interpretation: the importance of intra-class correlation coefficients (ICC) and their calculations based on mixed models, ANOVA, and variance estimates. Journal of toxicology and environmental health. Part B, Critical reviews 62 30067478
2019 A novel L1CAM isoform with angiogenic activity generated by NOVA2-mediated alternative splicing. eLife 54 30829570
2015 The alternative splicing factor Nova2 regulates vascular development and lumen formation. Nature communications 51 26446569
2006 Interpretation of ANOVA models for microarray data using PCA. Bioinformatics (Oxford, England) 42 17105717
2003 Noise sampling method: an ANOVA approach allowing robust selection of differentially regulated genes measured by DNA microarrays. Bioinformatics (Oxford, England) 36 12874046
2001 pasilla, the Drosophila homologue of the human Nova-1 and Nova-2 proteins, is required for normal secretion in the salivary gland. Developmental biology 36 11784037
2020 Circ_0000376, a Novel circRNA, Promotes the Progression of Non-Small Cell Lung Cancer Through Regulating the miR-1182/NOVA2 Network. Cancer management and research 35 32922073
2020 De Novo Frameshift Variants in the Neuronal Splicing Factor NOVA2 Result in a Common C-Terminal Extension and Cause a Severe Form of Neurodevelopmental Disorder. American journal of human genetics 34 32197073
2016 Comparing the Performance of Approaches for Testing the Homogeneity of Variance Assumption in One-Factor ANOVA Models. Educational and psychological measurement 34 29795915
2020 Circ_0072088 promotes the development of non-small cell lung cancer via the miR-377-5p/NOVA2 axis. Thoracic cancer 32 32524752
2019 The Alternative Splicing Regulator Nova2 Constrains Vascular Erk Signaling to Limit Specification of the Lymphatic Lineage. Developmental cell 30 31014480
2018 Upregulation of the alternative splicing factor NOVA2 in colorectal cancer vasculature. OncoTargets and therapy 30 30275709
2011 Identification of Critical Molecular Components in a Multiscale Cancer Model Based on the Integration of Monte Carlo, Resampling, and ANOVA. Frontiers in physiology 25 21779251
2009 Identification of differentially expressed subnetworks based on multivariate ANOVA. BMC bioinformatics 23 19405941
2018 Rapid Screening of DNA-Ligand Complexes via 2D-IR Spectroscopy and ANOVA-PCA. Analytical chemistry 21 29359920
2022 Circ-EIF3I facilitates proliferation, migration, and invasion of lung cancer via regulating the activity of Wnt/β-catenin pathway through the miR-1253/NOVA2 axis. Thoracic cancer 15 36193788
1997 ANOVA, a putative astrocytic RNA-binding protein gene that maps to chromosome 19q13.3. Neurogenetics 15 10735272
2011 Generic framework for high-dimensional fixed-effects ANOVA. Briefings in bioinformatics 14 22199378
2004 The operons, a criterion to compare the reliability of transcriptome analysis tools: ICA is more reliable than ANOVA, PLS and PCA. Computational biology and chemistry 14 15022635
2018 An ANOVA approach for statistical comparisons of brain networks. Scientific reports 13 29549369
2006 Testing non-additivity (interaction) in two-way ANOVA tables with no replication. Statistical methods in medical research 13 16477949
2022 De novo truncating NOVA2 variants affect alternative splicing and lead to heterogeneous neurodevelopmental phenotypes. Human mutation 12 35607920
2006 Parametric study of the biopotential equation for breast tumour identification using ANOVA and Taguchi method. Medical & biological engineering & computing 12 16929931
2006 Discrimination of shifts in a soil microbial community associated with TNT-contamination using a functional ANOVA of 16S rRNA hybridized to oligonucleotide microarrays. Environmental science & technology 12 17051772
2024 SpaceANOVA: Spatial Co-occurrence Analysis of Cell Types in Multiplex Imaging Data Using Point Process and Functional ANOVA. Journal of proteome research 11 38417823
2023 Alternative Splicing Changes Promoted by NOVA2 Upregulation in Endothelial Cells and Relevance for Gastric Cancer. International journal of molecular sciences 11 37175811
2020 Hsa_circ_0046263 Drives the Carcinogenesis and Metastasis of Non-Small Cell Lung Cancer Through the Promotion of NOVA2 by Absorbing Mir-940 as a Molecular Sponge. Cancer management and research 11 33364827
2018 Group-wise ANOVA simultaneous component analysis for designed omics experiments. Metabolomics : Official journal of the Metabolomic Society 11 29861703
2014 Specific recognition mechanism between RNA and the KH3 domain of Nova-2 protein. The journal of physical chemistry. B 10 25300025
2023 METTL14 reverses liver fibrosis by inhibiting NOVA2 through an m6A-YTHDF2-dependent mechanism. Hepatology communications 9 37534933
2014 Characterization of near-infrared spectral variance in the authentication of skim and nonfat dry milk powder collection using ANOVA-PCA, pooled-ANOVA, and partial least-squares regression. Journal of agricultural and food chemistry 9 25010570
2023 Circ_0004140 promotes lung adenocarcinoma progression by upregulating NOVA2 via sponging miR-330-5p. Thoracic cancer 8 37920146
2021 Circ_0001806 Promotes the Proliferation, Migration and Invasion of NSCLC Cells Through miR-1182/NOVA2 Axis. Cancer management and research 8 33854376
2010 Evidence obtained from ANOVA to reason cross-species infection and cross-subtype mutation in neuraminidases of influenza A viruses. Transboundary and emerging diseases 8 20545912
2023 Circ_0102231 inactivates the PI3K/AKT signaling pathway by regulating the miR-635/NOVA2 pathway to promote the progression of non-small cell lung cancer. Thoracic cancer 7 37864285
2022 PART1 destabilized by NOVA2 regulates blood-brain barrier permeability in endothelial cells via STAU1-mediated mRNA degradation. Gene 7 34990795
2010 Functional analysis: evaluation of response intensities--tailoring ANOVA for lists of expression subsets. BMC bioinformatics 7 20942918
2023 Angular limb deformity associated with TSPAN18, NRG3 and NOVA2 in Rambouillet rams. Scientific reports 6 37749158
2022 Circ_0016760 Serves as a Cancer Promoter in Non-small Cell Lung Cancer Through miR-876-3p/NOVA2 Axis. Biochemical genetics 6 35239092
2019 Two-factor ANOVA of SSH and RNA-seq analysis reveal development-associated Pi-starvation genes in oilseed rape. Planta 6 31165231
2024 NOVA2 regulates the properties of liver cancer stem cells and lenvatinib resistance in hepatocellular carcinoma via the Wnt pathway. Journal of gastrointestinal oncology 5 39279925
2020 Three way ANOVA for emulsion of carotenoids extracted in flaxseed oil from carrot bio-waste. Waste management (New York, N.Y.) 5 33360169
2001 Using Johnson's transformation and robust estimators with heteroscedastic test statistics: an examination of the effects of non-normality and heterogeneity in the non-orthogonal two-way ANOVA design. The British journal of mathematical and statistical psychology 5 11393903
2021 Magnetic Resonance Imaging (MRI) Differential Diagnosis of Meningiomas Using ANOVA. Contrast media & molecular imaging 4 34354552
2023 Effect of wheat roasting conditions and wheat type on short-wave infrared (SWIR) spectral data of whole and milled wheat by ANOVA-simultaneous component analysis. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy 3 37481843
2021 ANOVA-particle swarm optimization-based feature selection and gradient boosting machine classifier for improved protein-protein interaction prediction. Proteins 3 34528291
2020 ANOVA-HD: Analysis of variance when both input and output layers are high-dimensional. PloS one 3 33315963
2018 Detection of network motifs using three-way ANOVA. PloS one 3 30080876
2012 Combining multiple laser scans of spotted microarrays by means of a two-way ANOVA model. Statistical applications in genetics and molecular biology 3 22499702
2010 Alternative splicing disabled by Nova2. Neuron 3 20620865
2023 OmicPredict: a framework for omics data prediction using ANOVA-Firefly algorithm for feature selection. Computer methods in biomechanics and biomedical engineering 2 37842810
2013 Detection of epigenetic changes using ANOVA with spatially varying coefficients. Statistical applications in genetics and molecular biology 2 23502341
2011 Identification of differentially expressed genes for time-course microarray data based on modified RM ANOVA. IEEE/ACM transactions on computational biology and bioinformatics 2 21464508
2025 NOVA2 expression in pituitary gland and in functioning and non-functioning pituitary adenomas: a preliminary study. Acta neurochirurgica 1 40549212
2023 [Analysis of NOVA2 gene variant in a child with Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 36709943
2021 Autoregressive parametric modeling combined ANOVA approach for label-free-based cancerous and normal cells discrimination. Heliyon 1 34036199
2016 Patterns of Substitution Rate Variation at Many Nuclear Loci in Two Species Trios in the Brassicaceae Partitioned with ANOVA. Journal of molecular evolution 1 27592229
2006 Expression profilings of 39 genes selected by ANOVA could separate precursors of murine dendritic cells and macrophages. Biochemical and biophysical research communications 1 16603127
2026 RNA Toxicity and Interacting RNA-Binding Protein NOVA2 of (UUUCA)exp RNA Foci in Familial Cortical Myoclonic Tremor with Epilepsy. Movement disorders : official journal of the Movement Disorder Society 0 41850906
2026 STAT3-mediated transactivation of NOVA2 promotes lung adenocarcinoma metastasis by splicing SMAD4. Oncogene 0 41922577
2025 Melittin-loaded solid lipid nanoparticles inhibit pulmonary fibrosis via the NOVA2-TGF-β/Smads signaling pathway. International immunopharmacology 0 41418641
2024 Derivation of an induced pluripotent stem cell line (FDCHi014-A) from PBMCs of a seven-year-old patient with a truncating NOVA2 variant (c.625del). Stem cell research 0 38430735
2024 Bootstrap tests for simultaneous monotone ordering of effects in a two-way ANOVA. Biometrical journal. Biometrische Zeitschrift 0 38581103
2023 SpaceANOVA: Spatial co-occurrence analysis of cell types in multiplex imaging data using point process and functional ANOVA. bioRxiv : the preprint server for biology 0 37461579
2022 Method for identification of 10 SSR markers from monkey genomes and its statistical inference with One & Two-way ANOVA. MethodsX 0 36117677
2015 A Robust ANOVA Approach to Estimating a Phylogeny from Multiple Genes. Molecular biology and evolution 0 25841490

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