ITGA2B gene

The ITGA2B gene (ITGA2B stands for integrin subunit alpha 2b) is a protein-coding gene located on chromosome 17q21.31. An important paralog of this gene is ITGA8.

This gene encodes a member of the integrin alpha-chain protein family. The encoded preproprotein undergoes proteolytic processing, resulting in light and heavy chains that link via disulfide bridges to form a subunit of the alpha-IIb/beta-3 integrin cell adhesion receptor. This receptor plays a crucial role in the blood coagulation system by mediating the binding of activated platelets via fibrinogen. It is thus essential for platelet aggregation (Nurden AT et al. 2011).

Upregulation of the αIIb protein in platelets during sepsis is associated with an increased mortality rate. In animal studies, a decrease in ITGA2B levels leads to increased mortality in septic mice (Jiang J et al. 2023). Analysis of platelet transcriptome profiles (via RNA sequencing) demonstrates that ITGA2B upregulates the expression of PTPN6 in megakaryocytes via the transcription factors NF-κB1 and Rel. Furthermore, PTPN6 inhibits platelet apoptosis and necroptosis during sepsis by acting on the Ripk1/Ripk3/Mlkl and caspase-8 signaling pathways.

Biallelic pathogenic ITGA2B variants cause Glanzmann thrombasthenia, characterized by impaired platelet aggregation and a tendency toward mucocutaneous bleeding. Certain heterozygous variants, on the other hand, can cause autosomal-dominant macrothrombocytopenia characterized by large, reduced-number platelets. The mode of inheritance therefore depends on the specific variant and its effect on αIIbβ3.

Integrins are ubiquitously expressed adhesion molecules. They are cell surface receptors that exist as heterodimers composed of alpha and beta subunits. Under physiological conditions, integrins are highly glycosylated and contain a Ca²⁺ or Mg²⁺ ion, which is essential for ligand binding.

1. Ferrari S et al. (2026) Clinical and Genetic Characterization of 269 Patients With Suspected Inherited Platelet Disorders: The Padua Monocentric Experience. Int J Lab Hematol 48:856-865.
2. Jiang J et al. (2023) Platelet ITGA2B inhibits caspase-8 and Rip3/Mlkl-dependent platelet death via PTPN6 during sepsis. iScience 26:107414.
3. Nurden AT et al. (2011) “Glanzmann thrombasthenia: a review of ITGA2B and ITGB3 defects.” Blood 118:5996–6005.