XPNPEP2 Gene: Function, Expression, and Clinical Significance

XPNPEP2 encodes a membrane-bound form of X-prolyl aminopeptidase (aminopeptidase P), which catalyzes the removal of N-terminal amino acids from peptides with a proline residue in the penultimate position. This enzyme is involved in the metabolism of bradykinin and other vasoactive peptides. The gene is located on the X chromosome and is expressed in various tissues, with highest levels in kidney and small intestine. Variants in XPNPEP2 have been associated with altered bradykinin metabolism and adverse reactions to ACE inhibitors.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Bradykinin degradation (Reactome: R-HSA-2022377)

• Angiotensin II metabolism (Reactome: R-HSA-2022377)

XPNPEP2 encodes a 674-amino acid membrane-bound zinc metallopeptidase (UniProt O43895). The protein contains a transmembrane domain and an active site with the HEXXH motif characteristic of M24 family aminopeptidases. It specifically removes N-terminal amino acids from peptides with a proline residue at the penultimate position, playing a key role in the inactivation of bradykinin and other proline-containing peptides. The enzyme is expressed on the cell surface and is particularly abundant in kidney and intestinal brush border membranes.