PLOD2: Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2
Key enzyme in collagen cross-linking, associated with Bruck syndrome and cancer fibrosis
Gene Information Card
| Symbol | PLOD2 |
|---|---|
| Full Name | Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q24 |
| NCBI Gene ID | 5352 ncbi.nlm.nih.gov/gene/5352 |
| Ensembl ID | ENSG00000152952 |
| UniProt ID | O00469 |
| OMIM ID | 601865 |
| HGNC ID | 9082 |
| Aliases | LH2, LH-2, TLH, Bruck syndrome, lysyl hydroxylase 2 |
Description
PLOD2 encodes lysyl hydroxylase 2 (LH2), an enzyme that hydroxylates lysine residues in collagen telopeptides, a critical step for the formation of stable collagen cross-links. This gene is essential for bone and connective tissue integrity. Mutations cause Bruck syndrome (osteogenesis imperfecta with contractures). Overexpression is linked to fibrosis and tumor progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bruck syndrome 1 (BRKS1) | Loss-of-function mutations in PLOD2 impair telopeptide lysyl hydroxylation, leading to defective collagen cross-linking, bone fragility, and congenital joint contractures. | OMIM #259450; PubMed 10465113 |
| Osteogenesis imperfecta (OI) | PLOD2 mutations cause a recessive form of OI with contractures (Bruck syndrome), distinct from classical OI. | OMIM #601865; PubMed 10465113 |
| Cancer (fibrosis-related) | PLOD2 overexpression in tumors (e.g., breast, lung, glioma) promotes collagen cross-linking, matrix stiffening, and metastasis. | PubMed 23382250; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Skin | 10.2 | Medium |
| Bone | 8.9 | Medium |
| Breast | 7.1 | Low |
| Liver | 6.3 | Low |
| Kidney | 5.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 15.3 | High expression |
| MCF7 (breast cancer) | 9.8 | Medium expression |
| HepG2 (hepatocellular carcinoma) | 7.2 | Low expression |
| HT1080 (fibrosarcoma) | 18.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1082G>A (p.Gly361Asp) | Missense | Rare | Loss of function; associated with Bruck syndrome |
| c.1856C>T (p.Pro619Leu) | Missense | Rare | Loss of function; Bruck syndrome |
| c.2023C>T (p.Arg675*) | Nonsense | Rare | Premature stop; loss of function |
| c.1462G>A (p.Glu488Lys) | Missense | Rare | Likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Most PLOD2 mutations in Bruck syndrome are loss-of-function, reducing or abolishing lysyl hydroxylase activity, leading to defective collagen cross-linking.
Gain of Function (GOF)
Not reported in germline; overexpression in cancer may act as a gain-of-function at the expression level.
Dominant Negative (DN)
Not described for PLOD2.
View complete mutation data：
Gene Ontology (GO)
| • procollagen-lysine 5-dioxygenase activity (GO:0001540) | • iron ion binding (GO:0005506) |
| • oxidoreductase activity (GO:0016491) | • collagen fibril organization (GO:0030199) |
| • oxidation-reduction process (GO:0055114) | • endoplasmic reticulum (GO:0005783) |
Pathways
• Collagen biosynthesis and modifying enzymes (Reactome: R-HSA-1650814)
• Lysine degradation (KEGG: hsa00310)
• Extracellular matrix organization (Reactome: R-HSA-1474244)
Protein Summary
PLOD2 encodes lysyl hydroxylase 2 (LH2), a 737-amino acid protein localized to the endoplasmic reticulum. LH2 specifically hydroxylates lysine residues in the telopeptide regions of collagen types I and II, enabling the formation of stable pyridinoline cross-links essential for bone and connective tissue strength. The enzyme requires iron, 2-oxoglutarate, and ascorbate as cofactors. Mutations cause Bruck syndrome, while overexpression contributes to fibrosis and cancer metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PLOD2 Knockout HEK293 Cell Line | EDJ-KQ5484 | Human | 5352 | Details Get a Quote |
| PLOD2 Knockout HCT 116 Cell Line | EDJ-KQ27456 | Human | 5352 | Details Get a Quote |
| PLOD2 Knockout A-549 Cell Line | EDJ-KQ28705 | Human | 5352 | Details Get a Quote |
| PLOD2 Knockout HeLa Cell Line | EDJ-KQ28707 | Human | 5352 | Details Get a Quote |
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