IMPAD1 Human

The IMPAD1 gene is located on chromosome 8q12.1 . The gene encodes a protein that has a short N-terminal tail, a transmembrane domain, and an N-glycosylation site . The protein is known to colocalize with markers of the Golgi compartment in human skin fibroblasts .

IMPAD1 is involved in the dephosphorylation of inositol monophosphate to produce free inositol, which is a critical component of the phosphatidylinositol signaling pathway . This pathway is essential for various cellular functions, including cell growth, survival, and differentiation.

Mutations in the IMPAD1 gene have been associated with a rare genetic disorder known as chondrodysplasia with joint dislocations, GPAPP type . This condition is characterized by short stature, chondrodysplasia with brachydactyly, congenital joint dislocations, micrognathia, cleft palate, and facial dysmorphism . Studies have identified several homozygous mutations in the IMPAD1 gene in individuals with this condition .

Research on IMPAD1 has shown that it has robust 3-prime nucleotidase activity toward 3-prime phosphoadenosine 5-prime phosphate (PAP), and its activity is potently inhibited by lithium in a noncompetitive manner . This makes it a potential target for therapeutic interventions in conditions related to inositol metabolism.

In animal models, specifically Gpapp -/- mice, the absence of IMPAD1 leads to severe respiratory distress and dwarfism characterized by aberrant cartilage morphology . These findings highlight the importance of IMPAD1 in normal skeletal development and respiratory function.

Human recombinant IMPAD1 is produced using recombinant DNA technology, which involves inserting the human IMPAD1 gene into a suitable expression system, such as bacteria or yeast, to produce the protein in large quantities. This recombinant protein is used in various research applications to study its function, structure, and potential therapeutic uses.