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PLOD1

procollagen-lysine,2-oxoglutarate 5-dioxygenase 1

The PLOD1 gene provides instructions for producing lysyl hydroxylase 1, an enzyme vital for the proper formation and stability of collagen, a key component of connective tissues. PLOD1 is essential for modifying collagen, ensuring its structural integrity throughout the body.

Chromosome 1p36.22 Autosomal recessive HGNC:9081 Tier C
PLOD1 1p36.22 p arm q arm 1

PLOD1 is located on the short (p) arm of chromosome 1, at band 1p36.22. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 1 in the library →

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Clinical tests that include this

Carrier Screening panel
PLOD1 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The PLOD1 gene, also known as procollagen-lysine,2-oxoglutarate 5-dioxygenase 1, plays a crucial role in the development and maintenance of connective tissues. It provides the genetic blueprint for an enzyme called lysyl hydroxylase 1, which is critical for collagen maturation.

Collagen is the most abundant protein in the human body, forming the structural scaffolding for skin, bones, tendons, ligaments, and blood vessels. Proper function of the PLOD1 gene is therefore fundamental for tissue strength and integrity.

What the gene does

The PLOD1 gene encodes lysyl hydroxylase 1, an enzyme responsible for a specific chemical modification of collagen. This enzyme converts the amino acid lysine to hydroxylysine through a process called hydroxylation. Hydroxylysine residues are crucial for the formation of stable intermolecular cross-links within collagen fibres.

These cross-links are essential for collagen molecules to assemble into strong, organised fibrils, which provide structural support and mechanical strength to various body tissues. Without adequate hydroxylysine, collagen fibres can be weak and fragile, leading to issues with connective tissue integrity.

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Chromosome location

The PLOD1 gene is situated on chromosome 1, specifically at position 1p36.22. This location refers to the short (p) arm of chromosome 1, within band 36.22. The gene spans a region of the genome involved in coding for lysyl hydroxylase 1.

Protein structure

The lysyl hydroxylase 1 protein, encoded by the PLOD1 gene, comprises 727 amino acids. A key functional region of this protein is the Fe2OG dioxygenase domain, located towards the C-terminus, specifically spanning amino acids 636-727. This domain is crucial for the enzyme's hydroxylase activity, facilitating the conversion of lysine to hydroxylysine.

Domain map · 727 amino acids
Fe2OG dioxygenase (636-727)Fe2OG dioxygenase636-7271~364727
Domain - independent functional unit
🧬 Explore 3D structure on AlphaFold
UniProt:Q02809Length:727 aaStructure:AlphaFold

Key variants

Variants within the PLOD1 gene can alter the function of the lysyl hydroxylase 1 enzyme, impacting collagen stability. Over 30 different pathogenic variants have been identified, which can disrupt the protein's ability to properly modify collagen. These genetic changes are typically inherited in an autosomal recessive manner.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for PLOD1.
View all on ClinVar →

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.1097+1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.1261dup
Duplication
 p.Ala421fs Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.166C>T
single nucleotide variant
 p.Gln56Ter Pathogenic ★★☆☆ Familial thoracic aortic aneurysm and aortic dissection
c.1795del
Deletion
 p.Ile599fs Pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.1870del
Deletion
 p.Thr624fs Pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.1906C>T
single nucleotide variant
 p.Gln636Ter Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome
c.367C>T
single nucleotide variant
 p.Gln123Ter Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.467-2del
Deletion
 - Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.698_699insCCTCTGGCCTA
Insertion
 p.Asp234fs Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.979C>T
single nucleotide variant
 p.Gln327Ter Pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1

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

Pathogenic variants in the PLOD1 gene are primarily associated with the kyphoscoliotic type of Ehlers-Danlos syndrome. This inherited connective tissue disorder is characterised by symptoms such as unusually flexible joints (hypermobility), significant curvature of the spine (kyphoscoliosis), and fragile skin prone to bruising and scarring. The underlying cause is defective collagen, leading to weakened connective tissues throughout the body.

Inheritance pattern

Conditions caused by pathogenic PLOD1 variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous PLOD1 carrier status across ancestry groups?

UK clinical status

In the UK, the PLOD1 gene is included in several NHS Genomic Medicine Service (GMS) approved panels, indicating its clinical significance. It is part of the Arthrogryposis panel, the Ehlers Danlos syndrome with a likely monogenic cause panel, and the Foetal anomalies panel. Furthermore, it is listed on both the Thoracic aortic aneurysm or dissection panel and the GMS-specific Thoracic aortic aneurysm or dissection panel, suggesting its role in connective tissue disorders affecting the aorta. The gene is also recognised within the DDG2P (Deciphering Developmental Disorders) project.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Arthrogryposis · R83 NHS GMS → Ehlers Danlos syndrome with a likely monogenic cause · R101 NHS GMS → Fetal anomalies · R21 NHS GMS → Thoracic aortic aneurysm or dissection (GMS) · R125 NHS GMS → DDG2P NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main role of the PLOD1 gene?

The PLOD1 gene provides instructions for an enzyme called lysyl hydroxylase 1. This enzyme is crucial for modifying collagen, a protein that provides strength and support to many body tissues, by converting lysine to hydroxylysine.

How does PLOD1 relate to Ehlers-Danlos syndrome?

Pathogenic variants in the PLOD1 gene are a known cause of the kyphoscoliotic type of Ehlers-Danlos syndrome. These variants impair the enzyme's function, leading to defective collagen and characteristic symptoms like joint hypermobility and spinal curvature.

Is Ehlers-Danlos syndrome caused by PLOD1 variants an inherited condition?

Yes, the kyphoscoliotic type of Ehlers-Danlos syndrome caused by PLOD1 variants is inherited in an autosomal recessive pattern. This means an individual must inherit two copies of the altered gene (one from each parent) to develop the condition.

References

  1. Brady AF, Demirdas S, Fournel-Gigleux S. The Ehlers-Danlos syndromes, rare types. American journal of medical genetics. Part C, Seminars in medical genetics. 2017. PMID: 28306225
  2. Malfait F, Francomano C, Byers P. The 2017 international classification of the Ehlers-Danlos syndromes. American journal of medical genetics. Part C, Seminars in medical genetics. 2017. PMID: 28306229
  3. Rohrbach M, Vandersteen A, Yiş U. Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation. Orphanet journal of rare diseases. 2011. PMID: 21699693
  4. Giunta C, Bürer-Chambaz C, Steinmann B. Novel human pathological mutations. Gene symbol: PLOD1. Disease: Ehlers-Danlos syndrome type VIA, kyphoscoliotic type. Human genetics. 2009. PMID: 19320026
  5. Giunta C, Randolph A, Steinmann B. Mutation analysis of the PLOD1 gene: an efficient multistep approach to the molecular diagnosis of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA). Molecular genetics and metabolism. 2005. PMID: 15979919
  6. Eyre D, Shao P, Weis MA. The kyphoscoliotic type of Ehlers-Danlos syndrome (type VI): differential effects on the hydroxylation of lysine in collagens I and II revealed by analysis of cross-linked telopeptides from urine. Molecular genetics and metabolism. 2002. PMID: 12126935
  7. Heikkinen J, Toppinen T, Yeowell H. Duplication of seven exons in the lysyl hydroxylase gene is associated with longer forms of a repetitive sequence within the gene and is a common cause for the type VI variant of Ehlers-Danlos syndrome. American journal of human genetics. 1997. PMID: 8981946
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 4 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .