Carboxypeptidase N (EC 3.4.17.3) regulates the activity of
peptides such as
kinins and
anaphylatoxins. Although deficiency of
carboxypeptidase N (MIM 212070) produces a severe allergic syndrome, no human mutations have ever been described. Therefore, using archival genomic
DNA from a subject with documented
carboxypeptidase N deficiency, we sequenced CPN1 (MIM 603103), which encodes the catalytic subunit of
carboxypeptidase N. In the genomic
DNA of the proband, we discovered three CPN1 variants: (1) 385fsInsG, a frameshift mutation in exon 1 due to a single G insertion at
nucleotide 385; (2) 746G>A single-nucleotide polymorphism (SNP), a missense mutation in exon 3 that predicted substitution of
aspartic acid for the wild-type conserved
glycine at
amino acid 178 (G178D); and (3) IVS1 +6C>T, an SNP in intron 1. Among 128 normal Caucasians, the 385fsInsG mutation was absent and the G178D mutation had a frequency of 0.0078, suggesting that these were rare molecular events that likely contributed to the
carboxypeptidase N deficiency phenotype. The frequency of the IVS1 +6C>T polymorphism was 0.051. The
reagents described here provide tools for further study of association with clinical and biochemical phenotypes related to
allergy and immunity.