ORAI1

ORAI1 is a protein that in humans is encoded by the ORAI1 gene located on chromosome 12. It plays a crucial role in the regulation of intracellular calcium levels, which is vital for various cellular functions including muscle contraction, hormone secretion, and gene expression. The protein forms a part of the calcium release-activated calcium channel (CRAC) that mediates calcium influx into cells, essential for the activation of the immune system and other physiological processes.

Function

ORAI1 is integral to the process of store-operated calcium entry (SOCE). When the endoplasmic reticulum (ER) calcium stores are depleted, STIM1, a sensor protein in the ER membrane, undergoes a conformational change. This change allows it to interact with and activate ORAI1, leading to the opening of the CRAC channels on the plasma membrane and subsequent calcium influx. The influx of calcium through ORAI1 channels is critical for the activation of immune cells, including T cells and mast cells, and plays a role in various other cellular functions such as apoptosis (programmed cell death), metabolism, and gene expression.

Clinical Significance

Mutations in the ORAI1 gene have been associated with several immunodeficiency disorders. The most notable among these is the autosomal recessive condition known as Severe Combined Immunodeficiency (SCID) which is characterized by a severe defect in T cell activation and a susceptibility to infections. Patients with mutations in the ORAI1 gene exhibit impaired SOCE and defective T cell activation, highlighting the importance of ORAI1 in immune system function.

Additionally, alterations in ORAI1 expression or function have been implicated in various other diseases, including autoimmune diseases, cancer, and muscle disorders. The role of ORAI1 in these conditions is an area of active research, with the potential for developing new therapeutic strategies targeting the ORAI1-mediated calcium influx pathway.

Genetics

The ORAI1 gene is located on the short (p) arm of chromosome 12 at position 13.31, spanning approximately 7.2 kilobases. It consists of several exons that encode the ORAI1 protein. Genetic variations in the ORAI1 gene can affect the function of the protein and lead to disease.

See Also

• Calcium signaling
• Immunodeficiency
• Severe Combined Immunodeficiency (SCID)
• Store-operated calcium entry (SOCE)
• STIM1