HPSE2 Gene – Heparanase 2 (Inactive) | Function, Mutations & Disease Associations

HPSE2 (heparanase 2) encodes a protein homologous to heparanase (HPSE) but lacks endoglycosidase activity due to critical amino acid substitutions. It is involved in the regulation of heparan sulfate degradation, extracellular matrix remodeling, and cell signaling. Loss-of-function mutations in HPSE2 cause urofacial syndrome (UFS), an autosomal recessive disorder characterized by urinary tract dysfunction and facial grimacing. HPSE2 is also implicated in cancer progression, where it may act as a tumor suppressor by modulating heparan sulfate availability and growth factor signaling.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Heparan sulfate/heparin metabolism (Reactome: R-HSA-1638091)

• Degradation of the extracellular matrix (Reactome: R-HSA-1474228)

HPSE2 encodes a 592-amino acid protein (UniProt Q8WWQ2) that is a catalytically inactive homolog of heparanase. It is secreted and localizes to the extracellular matrix, where it binds heparan sulfate and modulates its degradation. The protein contains a glycosyl hydrolase domain but lacks critical residues for enzymatic activity. HPSE2 is thought to regulate cell adhesion, migration, and growth factor signaling by competing with active heparanase or by direct interaction with heparan sulfate chains. Its expression is highest in kidney and bladder, consistent with its role in urofacial syndrome.