NOTCH2NLC Gene - Neuronal Notch2 N-Terminal Like C
Essential regulator of neuronal development and implicated in neurodegenerative disorders
Gene Information Card
| Symbol | NOTCH2NLC |
|---|---|
| Full Name | Notch2 N-terminal like C |
| Gene Type | Protein coding |
| Chromosomal Location | 1q21.2 |
| NCBI Gene ID | 100996718 ncbi.nlm.nih.gov/gene/100996718 |
| Ensembl ID | ENSG00000273207 |
| UniProt ID | P0DPK4 |
| OMIM ID | 618025 |
| HGNC ID | 53879 |
| Aliases | N2NLC, NOTCH2NL-related, NOTCH2NL-C |
Description
NOTCH2NLC (Notch2 N-terminal like C) is a protein-coding gene located on chromosome 1q21.2. It belongs to the NOTCH2NL gene family, which arose from partial duplication of the NOTCH2 gene. The encoded protein is involved in neuronal development and cortical expansion. Pathogenic GGC repeat expansions in the 5' UTR of NOTCH2NLC are associated with neuronal intranuclear inclusion disease (NIID), a neurodegenerative disorder characterized by eosinophilic intranuclear inclusions in neurons and glial cells.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neuronal intranuclear inclusion disease (NIID) | GGC repeat expansion in the 5' UTR leads to abnormal protein aggregation and neuronal dysfunction | OMIM #618025; ClinVar; multiple case-control studies |
| Essential tremor | Some studies report association with intermediate-length GGC repeats | ClinVar; limited evidence |
| Parkinsonism | Rare reports of GGC repeat expansions in patients with parkinsonian features | ClinVar; case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Brain (cerebellum) | 8.3 | Low |
| Testis | 6.1 | Low |
| Heart | 2.4 | Not detected |
| Liver | 1.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| U-87 MG (glioblastoma) | 9.8 | Glial model |
| HEK293 (embryonic kidney) | 3.5 | Non-neuronal control |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| GGC repeat expansion (5' UTR) | Repeat expansion (typically >60 repeats) | Pathogenic in NIID; frequency varies by population | Gain of function; toxic RNA and protein aggregation |
| Intermediate GGC repeats (40-60) | Repeat expansion | Risk factor for essential tremor and parkinsonism | Possible altered expression |
Mutation functional classification
Loss of Function (LOF)
Not established; no clear loss-of-function mutations reported.
Gain of Function (GOF)
GGC repeat expansions produce toxic RNA foci and polyglycine-containing proteins (uN2CpolyG) that aggregate in nuclei.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • Notch signaling pathway (GO:0007219) |
| • nervous system development (GO:0007399) | • synapse (GO:0045202) |
| • nucleus (GO:0005634) |
Pathways
• Notch signaling pathway (Reactome: R-HSA-157118)
• Developmental biology (Reactome: R-HSA-1266738)
Protein Summary
The NOTCH2NLC protein (UniProt P0DPK4) is a 236-amino acid protein that shares high similarity with the N-terminal domain of NOTCH2. It localizes to the nucleus and is thought to modulate Notch signaling during neurogenesis. The protein contains an EGF-like domain and a DSL domain, which are typical of Notch ligands. Pathogenic GGC repeat expansions in the 5' UTR lead to the production of a toxic polyglycine-containing protein (uN2CpolyG) that forms intranuclear inclusions, a hallmark of NIID.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NOTCH2NLC Knockout HEK293 Cell Line | EDJ-KQ14452 | Human | 100996717 | Details Get a Quote |
| NOTCH2NLC Knockout A-549 Cell Line | EDJ-KQ44679 | Human | 100996717 | Details Get a Quote |
| NOTCH2NLC Knockout HCT 116 Cell Line | EDJ-KQ44680 | Human | 100996717 | Details Get a Quote |
| NOTCH2NLC Knockout HeLa Cell Line | EDJ-KQ44681 | Human | 100996717 | Details Get a Quote |
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