• 0
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
NOTCH2 (HGNC:7882) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
notch receptor 2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
No aliases found
%HI
3.21(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.12(Read more about gnomAD LOEUF score)
Cytoband
1p12
Genomic Coordinates
GRCh37/hg19: chr1:120454176-120612276 NCBI Ensembl UCSC
GRCh38/hg38: chr1:119911553-120069662 NCBI Ensembl UCSC
MANE Select Transcript
NM_024408.4 ENST00000256646.7 (Read more about MANE Select)
Function
Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus (PubMed:21378985, PubMed:21378989). Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). Involved in bone remodeling and ... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-3699
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
No Evidence for Haploinsufficiency (0)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
07/17/2014

Haploinsufficiency (HI) Score Details

HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • Alagille syndrome due to a NOTCH2 point mutation Monarch
HI Evidence Comments:
Though variantion in NOTCH2 has been associated with Alagile syndrome 2, the mechanism by which this occurs is unclear. Kamath et al. (2012) (PMID:22209762) note that two reported nonsense variants have been shown to result in mRNAs escaping nonsense-mediated decay, suggesting a mechanism other than haploinsufficiency. Specific gain of function mutations in NOTCH2 (resulting in signalling persistance) are associated with Hajdu-Cheney syndrome (OMIM#102500). It is important to note that many of the gain of function mutations resulting in Hajdu-Cheney are actually truncating mutations.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
While specific gain of function mutations in NOTCH2 (resulting in signalling persistance) are associated with Hajdu-Cheney syndrome (OMIM#102500), single copy gains have not yet been reported in the literature. It is unclear at the time of this review if NOTCH2 is subject to triplosensitivity.

Genomic View

Select assembly: (NC_000001.10) (NC_000001.11)