NOTCH2NLA
protein-codingnotch 2 N-terminal like A
Gene summary
Enables Notch binding activity. Involved in cerebral cortex development and positive regulation of Notch signaling pathway. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Jun 2026]
- NOTCH2NL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~82.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0011327
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NOTCH2NLA variants in ClinVar
No annotated ClinVar phenotypes.
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_203458.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 0 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 5 | 0 | 0 | 5 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_982283.2 | 4 | MANE Select | |
| Ensembl | ENSP00000354929.6 | 4 | MANE Select | |
| RefSeq | NP_001350935.1 | 5 | Standard | |
| RefSeq | NP_001382160.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- Notch signaling pathway
- cerebral cortex development
- cell differentiation
- positive regulation of Notch signaling pathway
Molecular Function
- Notch binding
- calcium ion binding
- protein binding
Cellular Component
- extracellular region
- cytoplasm
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Human-specific protein that promotes neural progenitor proliferation and evolutionary expansion of the brain neocortex by regulating the Notch signaling pathway (PubMed:29856954, PubMed:29856955, PubMed:29561261). Able to promote neural progenitor self-renewal, possibly by down-regulating neuronal differentiation genes, thereby delaying the differentiation of neuronal progenitors and leading to an overall final increase in neuronal production (PubMed:29856954). Acts by enhancing the Notch signaling pathway via two different mechanisms that probably work in parallel to reach the same effect (PubMed:29856954). Enhances Notch signaling pathway in a non-cell-autonomous manner via direct interaction with NOTCH2 (PubMed:29856954). Also promotes Notch signaling pathway in a cell-autonomous manner through inhibition of cis DLL1-NOTCH2 interactions, which promotes neuronal differentiation (By similarity). {ECO:0000250|UniProtKB:P0DPK3, ECO:0000269|PubMed:29561261, ECO:0000269|PubMed:29856954, ECO:0000269|PubMed:29856955}.;
- Disease
- DISEASE: Note=Defects in NOTCH2NLA may be a cause of chromosome 1q21.1 deletion/duplication syndrome (PubMed:29856954). Deletions of NOTCH2NL (NOTCH2NLA, NOTCH2NLB and/or NOTCH2NLC) are present in patients affected by microcephaly, whereas macrocephaly is observed in patients with NOTCH2NL duplications (PubMed:29856954). {ECO:0000269|PubMed:29856954}.;
Intolerance Scores
- RVIS EVS
- 0.66
- RVIS percentile EVS
- 84.27