NOVA2

Chr 19q13.32

NOVA alternative splicing regulator 2

Aliases:: ANOVA, NOVA-2
MANE:: ENST00000263257.6

OMIM: 601991 ↗NCBI: 4858 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

NOVA2 · Q9UNW9

v62025-08-01

Predicted Aligned Error matrix for NOVA2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

63.5/ 100

Low

492 residues

Confidence breakdown

Very high(≥ 90)21%
Confident(70–90)25%
Low(50–70)15%
Very low(< 50)39%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities
0.71
complex neurodevelopmental disorder
0.46
neurodevelopmental disorder
0.37
Severe intellectual disability
0.34
Intellectual disability
0.33
hereditary disease
0.19
dementia
0.07
neurodegenerative disease
0.04
ataxia telangiectasia
0.02
neuroblastoma
0.02

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

RNA-binding protein Nova-2

Functions to regulate alternative splicing in neurons by binding pre-mRNA in a sequence-specific manner to activate exon inclusion or exclusion (PubMed:32197073). It binds specifically to the sequences 5'-YCAY-3' and regulates splicing in only a subset of regulated exons (PubMed:10811881). Binding to an exonic 5'-YCAY-3' cluster changes the protein complexes assembled on pre-mRNA, blocking U1 snRNP binding and exon inclusion, whereas binding to an intronic 5'-YCAY-3' cluster enhances spliceosome assembly and exon inclusion. With NOVA1, they perform unique biological functions in different brain areas and cell types. Uniquely regulates alternative splicing events of a series of axon guidance related genes during cortical development, being essential for central nervous system development by regulating neural networks wiring. Regulates differentially alternative splicing on the same transcripts expressed in different neurons. This includes functional differences in transcripts expressed in cortical and cerebellar excitatory versus inhibitory neurons where is required for, respectively, development of laminar structure and motor coordination and synapse formation. Also the regulation the regulation of intron retention can sequester the trans-acting splicing factor PTBP2, acting as a variable cis-acting scaffolding platform for PTBP2 across various natural conditions (By similarity)