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PLOD2
procollagen-lysine,2-oxoglutarate 5-dioxygenase 2
PLOD2 is located on the long (q) arm of chromosome 3, at band 3q24. Arm ratio per GRCh38 - banding schematic.
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Overview
PLOD2 encodes an enzyme responsible for hydroxylating lysine residues in collagen molecules, a chemical modification essential for the formation of stable collagen cross-links. Collagen is the most abundant structural protein in the human body, providing mechanical support to skin, bone, blood vessels, and other tissues. The enzyme produced by PLOD2 works during collagen biosynthesis, attaching hydroxyl groups to lysine at specific positions along the collagen chain. These modifications enable subsequent cross-linking reactions that give mature collagen fibres their characteristic tensile strength. Disruption of PLOD2 function can alter the mechanical properties of connective tissue, with potential consequences for tissue integrity and wound healing.
What the gene does
The PLOD2 protein functions as a lysyl hydroxylase, catalysing the conversion of lysine residues to hydroxylysine within collagen precursor molecules. This enzymatic reaction requires 2-oxoglutarate, ferrous iron, and ascorbic acid as cofactors. Hydroxylysine residues serve as attachment sites for carbohydrate groups and participate in the formation of pyridinoline cross-links, which are particularly abundant in bone and cartilage. The enzyme acts on collagen chains before they are assembled into triple-helical structures and secreted from the cell. PLOD2 demonstrates substrate specificity for telopeptide regions of fibrillar collagens, distinguishing it from other lysyl hydroxylase isoforms that modify different regions of the collagen molecule. The pattern of hydroxylation influences the type and extent of cross-linking that occurs in the extracellular matrix, thereby affecting tissue stiffness and resistance to enzymatic degradation. Expression of PLOD2 varies across different tissues and developmental stages, with higher levels observed in tissues undergoing active remodelling or repair.
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Chromosome location
PLOD2 is located on chromosome 3 at cytogenetic band 3q24. This region of chromosome 3 contains several genes involved in connective tissue biology and extracellular matrix organisation. The precise exon structure and transcript variants of PLOD2 contribute to the regulation of enzyme activity in different cellular contexts.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variants in PLOD2 can alter enzyme activity, substrate specificity, or expression levels. Changes that reduce hydroxylase function may affect collagen cross-linking patterns and tissue mechanical properties. The clinical significance of many PLOD2 variants remains under investigation, as the relationship between specific sequence changes and measurable effects on connective tissue is complex and context-dependent.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1318C>T | p.Arg440Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Bruck syndrome 2 |
c.1417C>T | p.Arg473Ter | Pathogenic | ★★☆☆ | not provided |
c.1483C>T | p.Arg495Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Bruck syndrome 2 |
c.1500+1G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.1559dup | p.Val523fs | Pathogenic | ★★☆☆ | Osteogenesis imperfecta |
c.2038C>T | p.Arg680Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Bruck syndrome 2 |
c.8dup | p.Cys4fs | Pathogenic/Likely pathogenic | ★★☆☆ | Osteogenesis imperfecta |
c.1207_1208insA | p.Leu403fs | Pathogenic | ★☆☆☆ | not provided |
c.1501-2A>G | - | Pathogenic | ★☆☆☆ | Bruck syndrome 2 |
c.58del | p.Trp20fs | Pathogenic | ★☆☆☆ | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Research into PLOD2-associated conditions is ongoing. Alterations in PLOD2 activity have been studied in the context of fibrotic diseases, where excessive collagen deposition occurs, and in certain inherited connective tissue disorders where collagen quality is compromised. The gene's role in modulating the extracellular matrix has also drawn attention in cancer research, as tumour tissues often exhibit altered collagen architecture.
No disease links recorded for this gene in our reference set.
UK clinical status
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the PLOD2 enzyme do?
The PLOD2 enzyme adds hydroxyl groups to lysine amino acids within collagen chains, a modification necessary for forming strong cross-links between collagen molecules in connective tissue.
Why is collagen hydroxylation important?
Hydroxylation of lysine residues enables the formation of stable chemical cross-links that give collagen fibres their strength and resistance to degradation. Without adequate hydroxylation, connective tissue may be weaker and more susceptible to damage.
How common are PLOD2 variants?
The frequency of variants in PLOD2 varies across populations, and many variants have uncertain effects on enzyme function. Research continues to clarify which changes have clinical significance.