P4HA1 Gene: Prolyl 4-Hydroxylase Subunit Alpha 1 – Function, Mutations, and Disease Associations

P4HA1 encodes the alpha subunit of prolyl 4-hydroxylase, a key enzyme in collagen biosynthesis. This enzyme catalyzes the post-translational hydroxylation of proline residues in collagen chains, a critical step for proper collagen triple helix formation and secretion. P4HA1 is also induced under hypoxic conditions via HIF-1α, linking collagen metabolism to oxygen sensing and fibrosis.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Collagen biosynthesis and modifying enzymes

• HIF-1-alpha transcription factor network

• Endochondral ossification

P4HA1 is the catalytic alpha subunit of prolyl 4-hydroxylase, a tetrameric enzyme that hydroxylates proline residues in collagen chains. This modification is essential for collagen triple helix stability and secretion. The protein contains a conserved catalytic domain with a ferrous iron-binding site and a substrate-binding domain. P4HA1 expression is upregulated by hypoxia via HIF-1α, linking collagen metabolism to oxygen homeostasis. Mutations in P4HA1 cause rare forms of osteogenesis imperfecta, while overexpression is associated with fibrosis and cancer progression.