GENE REFERENCE / HGNC:7883

NOTCH3

notch receptor 3

protein-coding gene19p13.12Gene information

What does this gene do?

The NOTCH3 gene provides instructions for making a protein with one end (the intracellular end) that remains inside the cell, a middle (transmembrane) section that spans the cell membrane, and another end (the extracellular end) that projects from the outer surface of the cell. The NOTCH3 protein is called a receptor protein because certain other proteins, called ligands, attach (bind) to the extracellular end of NOTCH3, fitting like a key into a lock. This binding causes detachment of the intracellular end of the NOTCH3 protein, called the NOTCH3 intracellular domain, or NICD. The NICD enters the cell nucleus and helps control the activity (transcription) of other genes.

The NOTCH3 protein plays a key role in the function and survival of vascular smooth muscle cells, which are muscle cells that surround blood vessels. This protein is thought to be essential for the maintenance of blood vessels, including those that supply blood to the brain.

Source: MedlinePlus, National Library of Medicine. Source publication: 2022-06-21. Source review: 2016-07.

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
cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1MONDO:0000914 · Evaluated 2026-06-24	Autosomal dominant	DefinitiveNeurovascular Gene Curation Expert Panel
inherited thrombocytopeniaMONDO:0100241 · Evaluated 2025-11-03	Autosomal recessive	LimitedHemostasis/Thrombosis Gene Curation Expert Panel
pulmonary arterial hypertensionMONDO:0015924 · Evaluated 2022-11-03	Autosomal dominant	DisputedPulmonary Hypertension Gene Curation Expert Panel
cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1MONDO:0979867 · Evaluated 2026-08-26	Autosomal recessive	DefinitiveNeurovascular 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: 2,230
Submissions for variants in or overlapping this gene: 4,646
Submissions explicitly reporting this gene: 4,487
Alleles reported pathogenic / likely pathogenic: 338
VariationIDs with uncertain significance: 902
VariationIDs with conflicting classifications: 224

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 NOTCH3?

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 338 alleles in NOTCH3 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 NOTCH3.

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

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