FERMT3 Gene: Function, Mutations, and Associated Diseases (LAD-III)

The FERMT3 gene encodes kindlin-3, a member of the fermitin family of proteins that contain a FERM domain. Kindlin-3 is essential for the activation of integrins, which are cell surface receptors that mediate cell adhesion, migration, and signaling. It is primarily expressed in hematopoietic cells, including platelets, leukocytes, and erythroid cells. Mutations in FERMT3 lead to leukocyte adhesion deficiency type III (LAD-III), a rare autosomal recessive disorder characterized by severe bleeding, recurrent infections, and impaired wound healing. Kindlin-3 interacts with the cytoplasmic tail of integrin beta subunits and is required for the conformational change that allows high-affinity ligand binding.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Integrin signaling pathway

• Platelet activation

• Leukocyte transendothelial migration

• Focal adhesion

Kindlin-3 is a 667-amino acid protein with a FERM domain that binds to integrin beta tails. It is crucial for the inside-out signaling that activates integrins, enabling high-affinity ligand binding. In platelets, kindlin-3 is required for aggregation; in leukocytes, it is essential for adhesion and extravasation. Deficiency leads to LAD-III, characterized by bleeding and infections.