NEURL3

Chr 2

neuralized E3 ubiquitin protein ligase 3

Also known as: LINCR, RNF132

NCBI Gene: 93082 ENSG00000163121 UniProt: A8MQ27 OMIM: 617206

NEURL3 encodes an E3 ubiquitin-protein ligase that regulates the Notch signaling pathway by controlling the stability and activity of Notch ligands through targeted protein degradation. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and developmental regression. This represents a rare cause of early-onset epileptic encephalopathy affecting both neurological development and seizure control.

OMIM ResearchSummary from RefSeq, UniProt

Enables ubiquitin protein ligase activity. Involved in positive regulation of proteasomal protein catabolic process. Is active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

GOFmechanism

Clinical Summary— NEURL3

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ClinVar Variants

3 total variants — no pathogenic classifications of 3 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

0.5476th %ile

GOF

0.6639th %ile

LOF

0.3066th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

3 submitted variants in ClinVar

ClinVar

Classification Summary

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

Classification	LoF	Missense + Inframe	Non-coding	Synonymous
Pathogenic	—	—	—	—
Likely Pathogenic	—	—	—	—
VUS	—	—	—	—
Likely Benign	—	—	—	—
Benign	—	—	—	—
Total	—

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

12 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap NEURL3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →