NOTCH1 | SelfDecode | Genome Analysis

Summary of NOTCH1

The gene codes for a protein, notch 1. Mutations are linked to aortic valve disease, Adams-Oliver syndrome, T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and head and neck squamous cell carcinoma [R].

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The Function of NOTCH1

Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 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. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4+ and CD8+ cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO).

Protein names

Recommended name:

Neurogenic locus notch homolog protein 1

Alternative name(s):

Notch 1
hN1
Translocation-associated notch protein TAN-1
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NICD

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RS13300218 (NOTCH1) ??
RS41309764 (NOTCH1) ??

Top Gene-Substance Interactions

NOTCH1 Interacts with These Diseases

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Substances That Increase NOTCH1

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Substances That Decrease NOTCH1

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Advanced Summary

Adams-Oliver syndrome At least 15 mutations in the NOTCH1 gene have been found to cause Adams-Oliver syndrome, a condition characterized by areas of missing skin (aplasia cutis congenita), usually on the scalp, and malformations of the hands and feet. These mutations are usually inherited and are present in every cell of the body. Some of the NOTCH1 gene mutations involved in Adams-Oliver syndrome lead to production of an abnormally short protein that is likely broken down quickly, causing a shortage of Notch1. Other mutations change single protein building blocks (amino acids) in the Notch1 protein. These changes are thought to alter the structure of the protein, impairing its ability to function. Loss of Notch1 signaling may underlie blood vessel and heart abnormalities in people with Adams-Oliver syndrome. However, while these types of abnormalities are more common in affected individuals with NOTCH1 gene mutations than in those with a different gene mutation, some people with Notch1-related Adams-Oliver syndrome do not have blood vessel or heart abnormalities. It is not clear how loss of Notch1 function leads to the scalp and limb abnormalities characteristic of the condition. Researchers suggest these features may be due to abnormal blood vessel development before birth. critical congenital heart disease Genetics Home Reference provides information about critical congenital heart disease. head and neck squamous cell carcinoma Mutations in the NOTCH1 gene have been found in about 15 percent of head and neck squamous cell carcinomas (HNSCC). This type of cancerous tumor occurs in the moist lining of the mouth, nose, and throat. NOTCH1 gene mutations associated with this condition are acquired during a person's lifetime and are found only in tumor cells; these changes are known as somatic mutations. Mutations in the NOTCH1 gene may reduce or eliminate production of functional Notch1 protein or lead to production of a protein that is unable to participate in cell signaling. Without the tumor suppressor function of the Notch1 protein, cells can grow and divide without control, leading to tumor formation. other cancers NOTCH1 gene mutations have been found in other types of cancer, particularly blood cell cancers called T-cell acute lymphoblastic leukemia and chronic lymphocytic leukemia, and a type of lung cancer called non-small cell lung cancer. Unlike in HNSCC (described above), the NOTCH1 gene mutations found in these cancers abnormally turn on (activate) Notch1 signaling. The increased activity can lead to uncontrolled cell growth and division, which can result in the development of cancer. Researchers are working to understand how both activating and inactivating NOTCH1 gene mutations can lead to cancer development. other disorders Mutations in the NOTCH1 gene can impair normal heart development before birth, causing abnormalities of the heart and related structures. One such abnormality occurs in the valve that connects the aorta to the heart (the aortic valve). The aorta is the large blood vessel that distributes blood from the heart to the rest of the body. The aortic valve normally has three flaps, or cusps, that open to let blood leave the heart and come together to prevent blood from reentering the heart. However, in about 1 to 2 percent of people, the aortic valve has only two flaps, which is known as a bicuspid aortic valve. NOTCH1 gene mutations appear to be involved in 4 to 10 percent of bicuspid aortic valve cases. Individuals with a bicuspid aortic valve are at a higher than normal risk of developing other aortic abnormalities, such as a bulge in the wall of the aorta (thoracic aortic aneurysm) or a sudden tearing of the layers in the aorta wall (aortic dissection). In addition, accumulation of calcium on the aortic valve can occur in people with a bicuspid aortic valve. Researchers suspect that NOTCH1 gene mutations also play a role in the development of thoracic aortic aneurysms and in calcification of the valve. NOTCH1 gene mutations are also involved in critical congenital heart disease. Individuals with this condition have one or more specific heart abnormalities that affect the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.

The NOTCH1 gene provides instructions for making a protein called Notch1, a member of the Notch family of receptors. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Attachment of a ligand to the Notch1 receptor sends signals that are important for normal development of many tissues throughout the body, both before birth and after. Notch1 signaling helps determine the specialization of cells into certain cell types that perform particular functions in the body (cell fate determination). It also plays a role in cell growth and division (proliferation), maturation (differentiation), and self-destruction (apoptosis). The protein produced from the NOTCH1 gene has such diverse functions that the gene is considered both an oncogene and a tumor suppressor. Oncogenes typically promote cell proliferation or survival, and when mutated, they have the potential to cause normal cells to become cancerous. In contrast, tumor suppressors keep cells from growing and dividing too fast or in an uncontrolled way, preventing the development of cancer; mutations that impair tumor suppressors can lead to cancer development.

Conditions with Increased Gene Activity

Experimental Variables:

Condition	Change (log₂fold)	Comparison	Species	Experimental variables	Experiment name

Conditions with Decreased Gene Activity

Experimental Variables:

Condition	Change (log₂fold)	Comparison	Species	Experimental variables	Experiment name

Technical

The following transcription factors affect gene expression:

Tissue specificity:

In fetal tissues most abundant in spleen, brain stem and lung. Also present in most adult tissues where it is found mainly in lymphoid tissues.

Gene Pathways:

Molecular Function:

Biological Processes:

*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| p300| AOS5| AOVD1| AS27_13737| AS28_01090| Drosophila Notch homolog 1 (controlling the the ectodermal and neural cell fate in Drosophila)| H920_17125| hN1| I79_019276| lin-12| M91_09792| M959_09342| major type A protein| Mis6| Motch A| mT14| N1| N300_08786| N301_12472| N302_13073| N303_06196| N305_12834| N306_02294| N307_04845| N308_09218| N309_09925| N310_12413| N312_03483| N320_05104| N321_06684| N322_04926| N324_08198| N325_07685| N326_00864| N327_02271| N328_06489| N330_08116| N333_05289| N334_08523| N335_09955| neurogenic locus notch homolog protein 1| neurogenic locus notch homolog protein 1 preproprotein| Neurogenic locus notch like protein 1| Neurogenic locus notch-like protein 1| Neurogenic locus notch protein| Neurogenic locus notch protein 1| neurogenic locus notch protein 1-like protein| neurogenic locus notch protein homolog| Neurogenic locus notch protein like protein| NOTCH| NOTCH-1| notch 2| NOTCH2| Notch gene homolog 1| Notch homolog 1, translocation-associated| PAL_GLEAN10012684| tan1| translocation-associated notch protein TAN-1| transmembrane receptor Notch1| TREES_T100011163| UY3_08201| xnotch| xnotch1| x-notch-1| xotch| Y1Q_029491| Y956_02135| Z169_10168| notch1

NOTCH1 (Notch 1)

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