NOVA2

Chr 19

NOVA alternative splicing regulator 2

Also known as: ANOVA, NEDASB, NOVA-2, NOVA3

NCBI Gene: 4858 ENSG00000104967 UniProt: Q9UNW9

The NOVA2 protein regulates alternative splicing in neurons by binding to specific pre-mRNA sequences to control exon inclusion or exclusion, playing essential roles in cortical development, neural network wiring, and synapse formation. Mutations cause neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities, inherited in an autosomal dominant pattern. This gene is highly intolerant to loss-of-function variants (pLI = 0.98), reflecting its critical role in neurodevelopment.

ResearchSummary from RefSeq, OMIM, UniProt

Enables sequence-specific mRNA binding activity. Involved in neuron differentiation and regulation of alternative mRNA splicing, via spliceosome. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.24

Clinical Summary— NOVA2

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.24LOEUF

pLI 0.983

Z-score 3.25

OE 0.00 (0.00–0.24)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

4.35Z-score

OE missense 0.26 (0.21–0.31)

70 obs / 271.8 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.24)

0≤0.351.4

Missense OE?0.26 (0.21–0.31)

0≤0.61.4

Synonymous OE?0.69

0≤1.21.6

LoF obs/exp: 0 / 12.3Missense obs/exp: 70 / 271.8Syn Z: 2.88

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongNOVA2-related neurodevelopmental disorderOTHERAD

This gene — mechanism propensity

0.3494th %ile

GOF

0.4085th %ile

LOF

0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.24

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.