MUTATIONS AND DISEASES

Diseases Associated With NRP1 (8)

Glioma
T cell Leukemia/Lymphoma
Non-small cell Lung Cancer
COVID-19
Congenital Heart Defects

Major Mutations

Although some SNPs are prevalent within NRP1, none are directly linked to any specific disease. Instead, NRP1 functions as a pathway allowing the diseases mentioned above to affect those who develop them (39, 40, 41). NRP1 is a receptor for many diseases, and mutations we found did not have any link to diseases. We used several databases to explore mutations and diseases, but our efforts were vastly inconclusive.

Glioma

Disease Summary: Glioma is a common tumor that is found in the brain. Not only does the tumor grow within the brain matter, but it is also seen to grow within the brain tissue. Glioma is not limited to a certain age, it can be seen in people of all ages. Symptoms of gliomas include but are not limited to seizures, headaches, speech impairment, and dizziness. Diagnosis includes neurological testing of both cognitive and motor function, and brain scans such as MRI and CT scans (42). Depending on the grade of the tumor, there are several different ways to treat gliomas. The grade is based on tumor growth and aggressiveness.

Treatment and Inheritance: Several treatments include radiation, chemotherapy, and the most common choice of surgery. Oddly enough, only around 5% of gliomas are inherited through family genetics. However, race and gender seem to have an impact on developing glioma. It's been seen that Caucasians are more likely to develop gliomas more than any other race and that males are more common to have gliomas than females (43).

NRP1 Involvement: As mentioned on our protein function page, NRP1 plays a role in angiogenesis. Along with this, NRP1 is also known to enhance VEGF165 with its receptors. This plays a key role in the development of tumors as it has a direct link to growth factors of cells. It has been seen in several studies that the overexpression of NRP1 protein is extremely common in cancer cells since it’s known to promote tumor growth. NRP1 activates protein kinase signaling thus leading to an increase in tumor growth. It was also seen that NRP1 actually regulates tumor growth on its own without using the cell growth factor known as VEGF by interacting with another growth factor called FGF-2. All-in-all, it has just been recently discovered that NRP1 can be responsible for glioma tumor growth on its own without interacting with VEGF (44).

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Source: "NRP1 Promotes Tumor Progression"

The image above shows that in the presence of NRP1 tumor growth is greatly increased (44).

HTLV-1

Disease Summary and Inheritance: Adult T cell Leukemia/ lymphoma is commonly associated with infection from Human T cell Leukemia Retrovirus 1 (HTLV1). T cell leukemia/lymphoma is prevalent in adults, but very rare for children and it does not seem to display any inheritance patterns since viral infection is one of the main causes. The disease has no known gender prevalence and although the inheritance is not thought to deal with a genetic predisposition, there is still slight evidence of familial linkages (45). This disease affects T cells in the blood (leukemia) or lymph tissue (lymphoma). Symptoms include easily bleeding and bruising, extreme fatigue, swollen lymph nodes, and rash. These patients are also seen to be immunocompromised and are at high risk for infection (46, 45). T cell leukemia and lymphoma is often diagnosed by a complete blood count, which would reveal elevated T lymphocyte numbers in someone with this cancer. Other tests can be done to further test the progression and stage of this disease.

Treatment: Treatment of T cell leukemia/lymphoma consists of a wide variety of options, but ultimately it is up to the patient. This cancer can often be treated with chemotherapy, immunotherapy, and radiation therapy. These methods aim to stop the growth and spread of cancerous cells, but they can also harm healthy cells and cause adverse effects in patients. A more aggressive treatment could be a surgery; often, where the spleen is removed since that, is where white blood cells are mainly produced (46).

Interaction with NRP1: T cell lymphoma often occurs when an individual is infected by HTLV1. The pathway describing HTLV1 entry into cells, specifically CD 4 cells is highlighted on our protein function page. First, the HTLV will interact with heparan sulfate proteoglycans (HSPG), which interacts with NRP1. This interaction allows the virus to bind NRP1. GLUT1 is then brought into the complex and the virus can enter the cell. NRP1 is necessary for HTLV1 entry because it directly binds the virus (47).

Source: "HTLV-1 Entry"

The image above is a representation of HTLV-1 binding to NRP-1. In step 1, HTLV-1 SU and HSPG interact which then allows for HTLV-1 to attach to the cell surface. During step 2, NRP-1 is recruited for this mechanism after it binds to HSPG. Finally, in step 3, GLUT-1 is bound after conformational changes occur from the binding involved in step 2 (47).