GENE REFERENCE / HGNC:7882

NOTCH2

notch receptor 2

protein-coding gene1p12Gene information

What does this gene do?

The NOTCH2 gene provides instructions for making a protein that belongs to a large family of receptor proteins. Other proteins, called ligands, can fit into specific sites on receptor proteins, like a key into a lock. When a ligand attaches to the NOTCH2 receptor protein, it triggers a signaling pathway that is important for normal growth and development. Before birth, NOTCH2 signaling plays a role in the development of cells that will become part of the heart, liver, kidneys, teeth, bones, and other structures in the growing embryo. After birth, NOTCH2 signaling is involved in immune system function; tissue repair; and a process called bone remodeling, in which old bone is removed and new bone is created to replace it. NOTCH2 signaling also plays a role in the communication between neighboring cells.

The NOTCH2 receptor protein is embedded in the cell membrane and has several major parts, including a region that extends outward from the surface of the cell and a region that lies inside the cell. When a ligand binds to the outer portion of the NOTCH2 receptor protein, the inner portion separates from the rest of the protein. This part of the protein travels into the cell's nucleus, where it helps regulate the activity of specific genes.

Source: MedlinePlus, National Library of Medicine. Source publication: 2025-12-16. Source review: 2025-12.

ClinGen reviews

ClinGen reviews the evidence linking a particular gene to a condition. Each rating below describes the strength of that link. It does not classify a variant in your DNA file.

Condition	Inheritance	Evidence
Alagille syndromeMONDO:0007318 · Evaluated 2025-02-26	Autosomal dominant	DefinitiveKidney Cystic and Ciliopathy Disorders Gene Curation Expert Panel
acroosteolysis dominant typeMONDO:0007057 · Evaluated 2025-04-14	Autosomal dominant	DefinitiveKidney Cystic and Ciliopathy Disorders Gene Curation Expert Panel

ClinVar records

These numbers show what has been submitted to ClinVar. They cannot tell you how likely you are to have a condition.

Submitted alleles: 2,339
Submissions for variants in or overlapping this gene: 3,728
Submissions explicitly reporting this gene: 3,586
Alleles reported pathogenic / likely pathogenic: 112
VariationIDs with uncertain significance: 1,236
VariationIDs with conflicting classifications: 155

The rows count different things: alleles, submissions or VariationIDs. Their categories can overlap, so do not add them together. Pathogenic/likely pathogenic counts exclude structural variants that merely overlap a gene. A dash in the source means “not reported,” not zero.

NCBI produces the gene-summary file each week using counts recorded at the start of the month. The numbers may differ from those on the live ClinVar website. Read the field definitions ↗

View this gene in ClinVar ↗

YOUR DNA FILE

Can your DNA file tell you about NOTCH2?

From a DNA test kit (such as 23andMe, AncestryDNA or MyHeritage). These kits check a fixed list of about 600,000 to 700,000 positions across your whole genome. ClinVar lists 112 alleles in NOTCH2 reported as pathogenic or likely pathogenic. A kit checks only some of these positions, and often none of them.

From whole genome sequencing (a VCF file). Sequencing reads most of your genome. Your file lists the places where your DNA differs from the reference genome. Some regions are hard to sequence, including parts of some genes that have near-identical copies elsewhere, and a VCF file does not record which positions were read well.

If a variant is not in your file, that does not mean you don’t have it.

What BioDecode checks

BioDecode compares every variant in your file with ClinVar, on your own computer. For each match, it shows the ClinVar classification, the review status and the condition it was reported for. Your file is not uploaded.

A ClinVar classification applies to one particular variant and the condition it was reported for. It does not tell you about other variants in NOTCH2.

BioDecode cannot fill gaps in your test, diagnose a condition or replace clinical testing.

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