PLOD3: Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3
A key enzyme in collagen cross-linking and lysine hydroxylation, associated with connective tissue disorders and cancer.
Gene Information Card
| Symbol | PLOD3 |
|---|---|
| Full Name | procollagen-lysine,2-oxoglutarate 5-dioxygenase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 7q22.1 |
| NCBI Gene ID | 8985 ncbi.nlm.nih.gov/gene/8985 |
| Ensembl ID | ENSG00000106348 |
| UniProt ID | O60568 |
| OMIM ID | 603066 |
| HGNC ID | 9083 |
| Aliases | LH3, PLOD3_HUMAN, lysyl hydroxylase 3 |
Description
The PLOD3 gene encodes procollagen-lysine,2-oxoglutarate 5-dioxygenase 3, also known as lysyl hydroxylase 3 (LH3). This enzyme catalyzes the hydroxylation of lysine residues in collagen and other proteins, a critical step for the formation of stable collagen cross-links. PLOD3 is essential for normal connective tissue development and function. Mutations in PLOD3 are associated with a severe form of Ehlers-Danlos syndrome and have been implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ehlers-Danlos syndrome, kyphoscoliotic type 2 | Loss-of-function mutations in PLOD3 impair lysine hydroxylation, leading to defective collagen cross-linking and connective tissue fragility. | OMIM #612350 |
| Brittle cornea syndrome 2 | Mutations in PLOD3 reduce collagen stability in the cornea, causing thinning and fragility. | ClinVar |
| Cancer (various) | Overexpression of PLOD3 in tumors promotes collagen remodeling and metastasis; somatic mutations are observed in several cancer types. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 8.2 | Low |
| Breast | 15.3 | Medium |
| Colon | 12.1 | Medium |
| Heart | 6.5 | Low |
| Kidney | 18.7 | Medium |
| Liver | 22.4 | High |
| Lung | 14.0 | Medium |
| Pancreas | 10.9 | Medium |
| Skin | 20.1 | High |
| Spleen | 9.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 25.3 | Liver cancer cell line; high expression |
| A549 | 18.1 | Lung carcinoma cell line; moderate expression |
| MCF7 | 22.7 | Breast cancer cell line; high expression |
| HEK293 | 14.5 | Embryonic kidney cells; moderate expression |
| K562 | 8.9 | Leukemia cell line; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1082G>A (p.Gly361Asp) | Missense | Rare | Reduced enzyme activity; associated with Ehlers-Danlos syndrome |
| c.1462C>T (p.Arg488Ter) | Nonsense | Rare | Loss of function; causes premature termination |
| c.1670A>G (p.Tyr557Cys) | Missense | Rare | Impaired collagen binding; linked to brittle cornea syndrome |
| c.2035G>A (p.Glu679Lys) | Missense | Somatic (COSMIC) | Observed in colorectal cancer; functional impact unknown |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that reduce or abolish lysyl hydroxylase activity, leading to connective tissue disorders such as Ehlers-Danlos syndrome.
Gain of Function (GOF)
Not well documented; overexpression in tumors may confer gain-of-function in collagen remodeling and metastasis.
Dominant Negative (DN)
No clear dominant-negative mutations reported; most pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
| • endoplasmic reticulum lumen (GO:0005788) | • procollagen-lysine 5-dioxygenase activity (GO:0009791) |
| • peptidyl-lysine hydroxylation (GO:0018401) | • collagen fibril organization (GO:0030199) |
| • oxidation-reduction process (GO:0051211) |
Pathways
• Collagen biosynthesis and modifying enzymes
• Lysine degradation
• Metabolism of proteins
Protein Summary
PLOD3 encodes lysyl hydroxylase 3 (LH3), a 738-amino acid protein localized to the endoplasmic reticulum. LH3 hydroxylates lysine residues in collagen and other proteins, enabling the formation of stable intermolecular cross-links. The enzyme requires iron, 2-oxoglutarate, and ascorbate for activity. LH3 also possesses glucosyltransferase activity, transferring glucose to hydroxylysine residues. Defects in PLOD3 lead to connective tissue disorders, and its dysregulation is implicated in cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PLOD3 Knockout HEK293 Cell Line | EDJ-KQ6421 | Human | 8985 | Details Get a Quote |
| PLOD3 Knockout A-549 Cell Line | EDJ-KQ30470 | Human | 8985 | Details Get a Quote |
| PLOD3 Knockout HCT 116 Cell Line | EDJ-KQ30471 | Human | 8985 | Details Get a Quote |
| PLOD3 Knockout HeLa Cell Line | EDJ-KQ30472 | Human | 8985 | Details Get a Quote |
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