PLOD1 Gene

The PLOD1 gene (PLO stands for procollagen lysine,2-oxoglutarate 5-dioxygenase 1) is a protein-coding G located on chromosome 1p36.22. Two transcript variants encoding different isoforms have been found for this gene.

The encoded gene product a "lysylhydroxylase" is a membrane-bound homodimeric enzyme localized in the cisternae of the endoplasmic reticulum. The enzyme protein PLOD1 (cofactors iron and ascorbate) complexes with P3H3 and P3H4. This complex catalyzes the hydroxylation of lysine residues into collagen alpha chains. This process is required for the normal assembly and cross-linking of collagen fibrils. These resulting hydroxylysines serve as binding sites for carbohydrate moieties and are essential for the stability of intermolecular collagen cross-links.

Diseases associated with PLOD1 include kyphoscoliotic Ehlers-Danlos syndrome (formerly:type VI). These patients are deficient in lysylhydroxylase activity. An important paralog of this gene is PLOD2.

The diagnosis of PLOD1-related kyphoscoliotic Ehlers-Danlos syndrome is made in a subject with typical clinical findings and biallelic pathogenic (or likely pathogenic) PLOD1 variants identified by molecular genetic testing. If only one or no pathogenic variant is identified, testing for a markedly elevated urinary deoxypyridinoline to pyridinoline crosslink ratio measured by high-performance liquid chromatography (HPLC) may be required to confirm the diagnosis .

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