ArticleAmerican journal of human genetics2020
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.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- De novo variants in the poly(rC)-binding protein gene PCBP1 cause a neurodevelopmental disorder.Molecular psychiatry · 2026Article
- Single-cell proteomic landscape of the developing human brain.Nature biotechnology · 2026Article
- RNA-binding proteins: a comprehensive review of multifaceted regulatory mechanisms in neuroinflammation and implications in the pathogenesis of neurological disorders.Journal of neuroinflammation · 2026Review
- R-loop landscapes in the developing human brain are linked to neural differentiation and cell type-specific transcription.Translational psychiatry · 2026Article
- Embryonic spinocerebellar ataxia type 37-associated AUUUC repeat RNA causes neurodevelopmental defects.Disease models & mechanisms · 2026Article
- The Role of mRNA Alternative Processing in Mammalian Neurodevelopment.International journal of molecular sciences · 2025Review
- Comparative genomics sheds light on mammalian and avian gene regulation and phenotypic evolution.Nature communications · 2025Article
- Neuron-specific Agrin splicing by Nova RNA-binding proteins regulates conserved neuromuscular junction development in chordates.PLoS biology · 2025Article
- Dysregulated RNA-binding proteins and alternative splicing: Emerging roles in autism spectrum disorder.Molecules and cells · 2025Review
- mAutism research : official journal of the International Society for Autism Research · 2025Article
- DYRK1A roles in human neural progenitors.Frontiers in neuroscience · 2025Article
- A conserved RNA switch for acetylcholine receptor clustering at neuromuscular junctions in chordates.bioRxiv : the preprint server for biology · 2024Article
- Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects.Nature communications · 2023Article
- Characterizing the targets of transcription regulators by aggregating ChIP-seq and perturbation expression data sets.Genome research · 2023Article
- Circular RNAs: novel actors of Wnt signaling pathway in lung cancer progression.EXCLI journal · 2023Review
- Genomic regulatory sequences in the pathogenesis of bipolar disorder.Frontiers in psychiatry · 2023Review
- 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 · 2022Article
- Molecular convergence between Down syndrome and fragile X syndrome identified using human pluripotent stem cell models.Cell reports · 2022Article
- De novo truncating NOVA2 variants affect alternative splicing and lead to heterogeneous neurodevelopmental phenotypes.Human mutation · 2022Article
- Global developmental delay, systemic dysmorphism and epilepsy in a patient with a de novo U2AF2 variant.Journal of human genetics · 2021Article
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Authors and funding
28 authors at 12 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neuro-oncological ventral antigen 2 (NOVA2) protein is a major factor regulating neuron-specific alternative splicing (AS), previously associated with an acquired neurologic condition, the paraneoplastic opsoclonus-myoclonus ataxia (POMA). We report here six individuals with de novo frameshift variants in NOVA2 affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and abnormal brain MRI. The six variants lead to the same reading frame, adding a common proline rich C-terminal part instead of the last KH RNA binding domain. We detected 41 genes differentially spliced after NOVA2 downregulation in human neural cells. The NOVA2 variant protein shows decreased ability to bind target RNA sequences and to regulate target AS events. It also fails to complement the effect on neurite outgrowth induced by NOVA2 downregulation in vitro and to rescue alterations of retinotectal axonal pathfinding induced by loss of NOVA2 ortholog in zebrafish. Our results suggest a partial loss-of-function mechanism rather than a full heterozygous loss-of-function, although a specific contribution of the novel C-terminal extension cannot be excluded.
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