NOVA2 Gene - RNA Binding Protein in Neural Development and Disease

NOVA2 (neuro-oncological ventral antigen 2) encodes an RNA-binding protein that is part of the Nova family. It is predominantly expressed in neurons and regulates alternative splicing of pre-mRNAs involved in synaptic function and neuronal development. Autoantibodies against NOVA2 are associated with paraneoplastic opsoclonus-myoclonus ataxia (POMA), a neurological disorder often linked to breast or ovarian cancer. Loss-of-function mutations in NOVA2 cause a neurodevelopmental disorder characterized by intellectual disability, motor delay, and seizures.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Alternative splicing regulation by NOVA (Reactome: R-HSA-9013408)

• NOVA-dependent regulation of neuronal splicing (KEGG: hsa03040)

NOVA2 is a 510-amino acid RNA-binding protein containing three KH domains (hnRNP K homology) that specifically recognize YCAY motifs in pre-mRNA. It shuttles between nucleus and cytoplasm and regulates alternative splicing of genes critical for synaptic function, including GRIN1, GABRG2, and DCC. Autoantibodies against NOVA2 in POMA patients disrupt its splicing function, leading to neurological symptoms.