P4HB Gene: Prolyl 4-Hydroxylase Subunit Beta (PDIA1) – Function, Disease Associations, and Expression
Comprehensive biomedical overview of P4HB, encoding the beta subunit of prolyl 4-hydroxylase and protein disulfide isomerase, with roles in collagen synthesis, ER stress, and disease.
Gene Information Card
| Symbol | P4HB |
|---|---|
| Full Name | prolyl 4-hydroxylase subunit beta |
| Gene Type | protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 5034 ncbi.nlm.nih.gov/gene/5034 |
| Ensembl ID | ENSG00000185624 |
| UniProt ID | P07237 |
| OMIM ID | 176790 |
| HGNC ID | 8548 |
| Aliases | PDIA1, ERBA2L, DSI, P4HB, PROHB, CLCRP1, GIT, PDI, DSI, PO4HB |
Description
The P4HB gene encodes the beta subunit of prolyl 4-hydroxylase, a key enzyme in collagen biosynthesis, and also functions as a protein disulfide isomerase (PDI) in the endoplasmic reticulum. P4HB is involved in oxidative protein folding, redox homeostasis, and cellular stress responses. Mutations in P4HB have been linked to a rare form of osteogenesis imperfecta (Cole-Carpenter syndrome) and other connective tissue disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cole-Carpenter syndrome (osteogenesis imperfecta type) | Missense mutations in P4HB disrupt prolyl 4-hydroxylase activity, leading to defective collagen cross-linking and bone fragility. | ClinVar, OMIM |
| Idiopathic pulmonary fibrosis (IPF) | Overexpression of P4HB in lung fibroblasts promotes collagen deposition and fibrosis; inhibition reduces fibrosis in models. | PubMed (not directly cited, but evidence from literature; use ClinVar for variants) |
| Cancer (various) | P4HB is upregulated in several cancers, supporting tumor growth and metastasis via ER stress adaptation and redox regulation. | COSMIC, PubMed (not directly cited) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High (nTPM ~ 1000) | High |
| Pancreas | High (nTPM ~ 800) | High |
| Kidney | Moderate (nTPM ~ 500) | Moderate |
| Lung | Moderate (nTPM ~ 400) | Moderate |
| Brain | Low (nTPM ~ 100) | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | High | High expression consistent with liver origin |
| A549 (lung carcinoma) | Moderate | Moderate expression; relevant to fibrosis studies |
| MCF7 (breast cancer) | Moderate | Moderate expression; role in ER stress |
| K562 (leukemia) | Low | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1178A>G (p.Tyr393Cys) | Missense | Rare (found in Cole-Carpenter syndrome) | Disrupts PDI activity and collagen hydroxylation |
| c.1216A>G (p.Arg406Gly) | Missense | Rare (found in Cole-Carpenter syndrome) | Impairs enzyme function |
| c.1033C>T (p.Arg345Cys) | Missense | Rare (found in osteogenesis imperfecta) | Affects protein stability and activity |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in P4HB reduce prolyl 4-hydroxylase and PDI activity, leading to defective collagen processing and osteogenesis imperfecta.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression in cancer may act as an oncogenic driver via enhanced ER stress adaptation.
Dominant Negative (DN)
Some P4HB mutations may exert dominant-negative effects by forming inactive heterodimers with the alpha subunit, impairing overall enzyme function.
View complete mutation data：
Gene Ontology (GO)
| • protein disulfide isomerase activity | • prolyl 4-hydroxylase activity |
| • chaperone binding | • endoplasmic reticulum lumen |
| • response to endoplasmic reticulum stress | • collagen biosynthetic process |
| • cell redox homeostasis | • protein folding |
Pathways
• Collagen biosynthesis and modifying enzymes
• Endoplasmic reticulum (ER) stress response (unfolded protein response)
• Protein processing in endoplasmic reticulum
• Redox regulation and oxidative stress response
Protein Summary
The P4HB protein (also known as PDI) is a multifunctional enzyme located primarily in the endoplasmic reticulum. It catalyzes the formation and isomerization of disulfide bonds during protein folding, and as the beta subunit of prolyl 4-hydroxylase, it hydroxylates proline residues in collagen, essential for triple helix stability. P4HB also acts as a chaperone and participates in redox signaling. Its dysfunction is linked to connective tissue disorders and cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| P4HB Knockout HEK293 Cell Line | EDJ-KQ3165 | Human | 5034 | Details Get a Quote |
| P4HB Knockout A-549 Cell Line | EDJ-KQ25934 | Human | 5034 | Details Get a Quote |
| P4HB Knockout HCT 116 Cell Line | EDJ-KQ25936 | Human | 5034 | Details Get a Quote |
| P4HB Knockout HeLa Cell Line | EDJ-KQ25937 | Human | 5034 | Details Get a Quote |
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