PTEN and Cowden syndrome 1: The PTEN gene has two main domains: the N-terminal region, which includes the phosphatase domain, containing the PTEN active site in exon 5, and the C-terminal region, which includes the C2 domain, that binds to phospholipids and positions the catalytic domain on the membrane.4) According to a study investigating cancer risk and genotype–phenotype correlations in 22 Japanese patients with CS, 12 had N-terminal-PTEN variants (11 in the phosphatase domain) and 10 had C-terminal-PTEN variants (C2 domain).