NOTCH2NLC
Chr 1ADnotch 2 N-terminal like C
Also known as: ETM6, NIID, OPDM3
NOTCH2NLC encodes a human-specific protein that promotes neural progenitor proliferation and regulates Notch signaling during cerebral cortex development. Mutations cause autosomal dominant neuronal intranuclear inclusion disease, oculopharyngodistal myopathy 3, and hereditary essential tremor 6. These conditions primarily affect the nervous system and skeletal muscle, with neuronal intranuclear inclusion disease representing a particularly severe neurodegenerative disorder.
Some data sources returned errors (1)
gnomad: Error: Gene not found
Population Genetics & Constraint
Constraint data not available from gnomAD.
The highest-scoring mechanism for this gene is gain-of-function.
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
5 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 4 |
Likely Pathogenic | — | — | — | — | 0 |
VUS | — | — | — | — | 1 |
Likely Benign | — | — | — | — | 0 |
Benign | — | — | — | — | 0 |
| Total | — | 5 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NOTCH2NLC · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Long-read Genome Sequencing for the Molecular Diagnosis of Dystonia
NOT YET RECRUITINGThe Benefits of Long-read High-throughput Genomic Sequencing for the Causal Diagnosis of Cerebellar Ataxias
RECRUITINGRepetitive Transcranial Magnetic Stimulation Therapy in Essential Tremor
RECRUITINGExternal Resources
Links to major genomics databases and tools