What is the Origin of PTPN22 Gene?

The gene name is an acronym for Protein Tyrosine Phosphatase, Non-Receptor Type 22, and its discovery was central to understanding the molecular genetics of autoimmunity. The identification of its high-risk polymorphism through large-scale genetic screening cemented its role as a master regulator in the pathogenesis of multiple autoimmune endocrinopathies.

What is the Mechanism of PTPN22 Gene?

Lyp, the protein product of PTPN22, functions by dephosphorylating key signaling molecules within T-cells, effectively dampening the activation signal received through the T-cell receptor. The high-risk variant of PTPN22 is believed to be a "gain-of-function" mutation that excessively inhibits T-cell signaling, potentially leading to defects in the negative selection process or regulatory T-cell function. This dysregulation compromises immunological tolerance, allowing self-reactive T-cells to escape control.

PTPN22 Gene ∞ Area

PTPN22 Gene

Meaning

The PTPN22 gene encodes the Lymphoid-specific tyrosine phosphatase (Lyp in humans), an intracellular enzyme that acts as a key negative regulator of T-cell activation and signaling pathways. Polymorphisms within this gene, particularly the R620W variant, are among the strongest genetic risk factors for a wide spectrum of human autoimmune diseases, including Type 1 Diabetes and Graves’ disease. This gene’s function is critical for maintaining the delicate balance of immune tolerance and preventing self-reactivity.