P4HA2
Prolyl 4-Hydroxylase Subunit Alpha 2
Gene Information Card
| Symbol | P4HA2 |
|---|---|
| Full Name | Prolyl 4-Hydroxylase Subunit Alpha 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q31.1 |
| NCBI Gene ID | 8974 ncbi.nlm.nih.gov/gene/8974 |
| Ensembl ID | ENSG00000113594 |
| UniProt ID | O15460 |
| OMIM ID | 600608 |
| HGNC ID | 8547 |
| Aliases | P4HA2, P4HA, PH, P4H-alpha-2 |
Description
P4HA2 encodes the alpha subunit of prolyl 4-hydroxylase, a key enzyme in collagen biosynthesis. This enzyme catalyzes the formation of 4-hydroxyproline in collagen and other proteins with collagen-like sequences, a post-translational modification essential for proper collagen triple helix formation and stability. P4HA2 is induced under hypoxic conditions via HIF-1α and plays roles in fibrosis, cancer progression, and extracellular matrix remodeling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteogenesis Imperfecta (OI) | Mutations in P4HA2 impair collagen hydroxylation, leading to brittle bones and connective tissue defects. | ClinVar, OMIM |
| Idiopathic Pulmonary Fibrosis (IPF) | Upregulation of P4HA2 in lung fibroblasts increases collagen deposition and fibrosis. | NCBI Gene, PubMed |
| Breast Cancer | Overexpression of P4HA2 promotes tumor growth, invasion, and metastasis via collagen remodeling. | COSMIC, PubMed |
| Colorectal Cancer | P4HA2 is upregulated and associated with poor prognosis; contributes to tumor microenvironment stiffening. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Lung | 10.3 | Medium |
| Kidney | 8.7 | Medium |
| Heart | 6.2 | Low |
| Brain | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.8 | Hepatocellular carcinoma cell line |
| A549 | 11.4 | Lung adenocarcinoma cell line |
| MCF7 | 9.6 | Breast cancer cell line |
| HEK293 | 7.3 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1120G>A (p.Gly374Arg) | Missense | <0.01% | Reduced enzyme activity; associated with OI |
| c.1483C>T (p.Arg495Trp) | Missense | <0.01% | Impaired collagen hydroxylation; OI |
| c.1655G>A (p.Arg552Gln) | Missense | <0.01% | Dominant negative effect; OI |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Gly374Arg) reduce catalytic activity, leading to underhydroxylated collagen and OI.
Gain of Function (GOF)
Not well documented; overexpression in cancer may act as a gain-of-function by increasing collagen deposition.
Dominant Negative (DN)
p.Arg552Gln mutation exerts dominant negative effect by disrupting subunit dimerization.
View complete mutation data：
Gene Ontology (GO)
| • procollagen-proline 4-dioxygenase activity | • L-ascorbic acid binding |
| • iron ion binding | • collagen biosynthetic process |
| • peptidyl-proline hydroxylation to 4-hydroxy-L-proline | • response to hypoxia |
| • extracellular matrix organization |
Pathways
• Collagen biosynthesis and modifying enzymes
• HIF-1 signaling pathway
• ECM-receptor interaction
• Protein hydroxylation
Protein Summary
P4HA2 encodes the alpha-2 subunit of prolyl 4-hydroxylase, a tetrameric enzyme composed of two alpha and two beta subunits. The alpha subunit contains the catalytic site and requires Fe2+, 2-oxoglutarate, and ascorbate for activity. The enzyme hydroxylates proline residues in collagen chains, stabilizing the triple helix. P4HA2 is highly expressed in tissues with active collagen synthesis and is upregulated in fibrotic diseases and cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| P4HA2 Knockout HEK293 Cell Line | EDJ-KQ6417 | Human | 8974 | Details Get a Quote |
| P4HA2 Knockout A-549 Cell Line | EDJ-KQ30464 | Human | 8974 | Details Get a Quote |
| P4HA2 Knockout HCT 116 Cell Line | EDJ-KQ30465 | Human | 8974 | Details Get a Quote |
| P4HA2 Knockout HeLa Cell Line | EDJ-KQ30466 | Human | 8974 | Details Get a Quote |
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